Data compiled during research into adverse effects of oophorectomy (ovary removal). For more information, or with questions, please email: info@gynreform.com.

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Cit. # Description Title and Author URL
1 Rates of ischemic heart disease were 7-fold higher in women with a history of oophorectomy (ovary removal) younger than 45 years

Should the ovaries be removed or retained at the time of hysterectomy for benign disease? M. Hickey 1 , M. Ambekar, and I. Hammond School of Women’s and Infants’ Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia, 2009
and
Løkkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT.
The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas 2006;53:226-233.

http://humupd.oxfordjournals. org/content/16/2/131.long

and

The_association_between_early_ menopause_and_risk_of_ ischaemic_heart_disease_ influence_of_Hormone_Therapy/ links/ 02e7e53b1c1ad5a703000000.pdf

2 Heart disease, number 1 killer, greater than all cancers combined The Heart Foundation & the CDC

http://www.theheartfoundation. org/heart-disease-facts/heart- disease-statistics/

http://mchb.hrsa.gov/publications/pdfs/womenhealth2008.pdf

3 information about the endocrine system, including ovaries/testes (aka gonads) - does not include information about the ovaries production of androgens nor about their role in continuing to produce hormones for a woman's entire life. Endocrine Society: Endocrine Glands and Types of Hormones

http://www.hormone.org/hormones-and-health/endocrine-glands-and-types-of-hormones

4 Comparing CVD mortality in women who didn't have either ovary out to ones who had one to ones who had both out over 37 year timespan. (2,383 none. 1,274 one. 1,091 both.) .82 hr mortality one out (less). Women who had both out before age 45 were 44% more likely to have a CV event, and 84% more likely for women who didn't use estrogen. Menopause. 2009 Jan–Feb; 16(1): 15–23. doi: 10.1097/gme.0b013e31818888f7 PMCID: PMC2755630 NIHMSID: NIHMS84682 Increased cardiovascular mortality following early bilateral oophorectomy Cathleen M. Rivera, MD,1 Brandon R. Grossardt, MS,2 Deborah J. Rhodes, MD,1 Robert D. Brown, Jr., MD, MPH,3 Véronique L. Roger, MD, MPH,4,5 L. Joseph Melton, III, MD, MPH,5 and Walter A. Rocca, MD, MPH3,5 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755630/
5 Removal of ovaries linked to premature death, overall mortality, cardiovascular disease, cognitive impairment or dementia, Parkinson's disease, psychological well-being, sexual function, osteoporosis Published in final edited form as: Menopause Int. 2008; 14(3): 111–116. doi: 10.1258/mi.2008.008016 PMCID: PMC2585770 NIHMSID: NIHMS59499 Prophylactic oophorectomy in pre-menopausal women and long term health – a review Lynne T. Shuster,* Bobbie S. Gostout,† Brandon R. Grossardt,‡ and Walter A. Rocca§ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585770/
6

Oophorectomy - Premature death, hot flashes, vaginal dryness, depression or anxiety, disease, memory problems, decreased sex drive, osteoporosis

Oophorectomy (ovary removal surgery) - Mayo Clinic http://www.mayoclinic.org/tests-procedures/oophorectomy/basics/risks/prc-20012991
7 Studied oophorectomy and mortality due to ovarian cancer, breast cancer, coronary heart disease, hip fracture, and stroke. Found that mortality in women who had surgery aged 45 and under had a 67% greater mortality risk over 37 years than intact women. Not found in unilateral oophorectomy, only when both removed. Lancet Oncol. 2006 Oct;7(10):821-8. Survival patterns after oophorectomy in pre-menopausal women: a population-based cohort study. Rocca WA1, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd. http://www.ncbi.nlm.nih.gov/pubmed/17012044
8 Cardiovascular, psychosexual, cognitive, mental health negative impacts of removal of ovaries Hum Reprod Update. 2010 Mar-Apr;16(2):131-41. doi: 10.1093/humupd/dmp037. Epub 2009 Sep 30. Should the ovaries be removed or retained at the time of hysterectomy for benign disease? Hickey M1, Ambekar M, Hammond I.

http://www.ncbi.nlm.nih.gov/pubmed/19793841
and
http://www.mrcogcourse.com/MRCOG_course/MRCOG_Blog/ Entries/2010/2/7_Should_the_ ovaries_be_removed_at_the_ time_of_hysterectomy_for_ benign_disease_files/BSOeTAH. pdf

9 Long-term negative effects on cognitive function of removing ovaries before menopause. Menopause at or before the age of 40 years, both premature bilateral ovariectomy and premature ovarian failure (non-surgical loss of ovarian function), was associated with worse verbal fluency (OR 1.56, 95%CI 1.12-1.87, P=0.004) and visual memory (OR 1.39, 95%CI 1.09-1.77, P=0.007) in later life. HT at the time of premature menopause appeared beneficial for later-life visual memory but increased the risk of poor verbal fluency. Type of menopause was not significantly associated with cognitive function. Premature menopause was associated with a 30% increased risk of decline in psychomotor speed and global cognitive function over 7 years. CONCLUSION: Both premature surgical menopause and premature ovarian failure were associated with long-term negative effects on cognitive function, which are not entirely offset by menopausal HT. In terms of surgical menopause, these results suggest that the potential long-term effects on cognitive function should form part of the risk/benefit ratio when considering ovariectomy in younger women. BJOG. 2014 Dec;121(13):1729-39. doi: 10.1111/1471-0528.12828. Epub 2014 May 7. Impact of a premature menopause on cognitive function in later life. Ryan J1, Scali J, Carrière I, Amieva H, Rouaud O, Berr C, Ritchie K, Ancelin ML. http://www.ncbi.nlm.nih.gov/pubmed/24802975
10 Women at an average risk of ovarian cancer benefit from ovarian conservation (not removing ovaries) until at least age 65 Menopause. 2007 May-Jun;14(3 Pt 2):580-5. Elective oophorectomy for benign gynecological disorders. Shoupe D1, Parker WH, Broder MS, Liu Z, Farquhar C, Berek JS. http://www.ncbi.nlm.nih.gov/pubmed/17476148
11 Increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other issues. Estrogen alone may not eliminate all adverse outcomes. Maturitas. 2010 Feb;65(2):161-6. doi: 10.1016/j.maturitas.2009.08. 003. Epub 2009 Sep 5. Premature menopause or early menopause: long-term health consequences. Shuster LT1, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. http://www.ncbi.nlm.nih.gov/pubmed/19733988
12 Ovary removal is associated with more severe psychological, vasomotor (hot flashes), and somatic (body) symptoms, as well as more significant sexual dysfunction than women who went through menopause. Climacteric. 2009 Oct;12(5):404-9. doi: 10.1080/13697130902780846. Climacteric symptoms in women undergoing risk-reducing bilateral salpingo-oophorectomy. Benshushan A1, Rojansky N, Chaviv M, Arbel-Alon S, Benmeir A, Imbar T, Brzezinski A. http://www.ncbi.nlm.nih.gov/pubmed/19479488
13 Women who had a hysterectomy with their ovaries removed (oophorectomy) had greater increases in BMI (body mass index) in years following surgery than women who went through menopause. Int J Obes (Lond). 2013 Jun;37(6):809-13. doi: 10.1038/ijo.2012.164. Epub 2012 Sep 25. Body mass index following natural menopause and hysterectomy with and without bilateral oophorectomy. Gibson CJ1, Thurston RC, El Khoudary SR, Sutton-Tyrrell K, Matthews KA. http://www.ncbi.nlm.nih.gov/ pubmed/23007036
14 Women whose ovaries were removed (oophorectomy/ovariectomy) have a decreased risk of breast cancer and ovarian cancer, but an increased risk of all-cause mortality (dying for any reason), fatal and non-fatal coronary heart disease, and lung cancer. In no age group was it associated with increased survival. Obstet Gynecol. 2009 May;113(5):1027-37. doi: 10.1097/AOG.0b013e3181a11c64. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study. Parker WH1, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, Shoupe D, Berek JS, Hankinson S, Manson JE.

http://www.ncbi.nlm.nih.gov/ pubmed/19384117

15 Increased risk of coronary heart disease, hip fracture, osteoporosis, breast cancer, stroke Clin Obstet Gynecol. 2007 Jun;50(2):354-61. Ovarian conservation at the time of hysterectomy for benign disease. Parker WH1, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. http://www.ncbi.nlm.nih.gov/ pubmed/17513923
16 Due to the disruption of endocrine chemistry (dopamine, serotonin, norepinephrine, oxytocin), ovary removal is associated with an increased long-term risk of depressive and anxiety symptoms Menopause. 2008 Nov-Dec;15(6):1050-9. doi: 10.1097/gme.0b013e318174f155. Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy. Rocca WA1, Grossardt BR, Geda YE, Gostout BS, Bower JH, Maraganore DM, de Andrade M, Melton LJ 3rd. http://www.ncbi.nlm.nih.gov/ pubmed/18724263
17 The potential negative effects of ovary removal, decreased cognition and sexual function and increased risk of osteoporosis and cardiac mortality, outweigh the benefits for women at average risk of ovarian cancer and merit a review of pros and cons with patients and a consideration of their individual circumstances and health risks Menopause. 2013 Jan;20(1):110-4. doi: 10.1097/gme.0b013e31825a27ab. Oophorectomy: the debate between ovarian conservation and elective oophorectomy. Erekson EA1, Martin DK, Ratner ES.

http://www.ncbi.nlm.nih.gov/ pubmed/22929033

18 Years after hysterectomy, women who had ovaries removed had 80% decreased libido, 82% difficulty with sexual arousal, and 69% vaginal dryness compared to women who'd had endometrial ablation Health Expect. 2005 Sep;8(3):234-43. Psychosexual health 5 years after hysterectomy: population-based comparison with endometrial ablation for dysfunctional uterine bleeding. McPherson K1, Herbert A, Judge A, Clarke A, Bridgman S, Maresh M, Overton C. http://www.ncbi.nlm.nih.gov/ pubmed/16098153
19 Removing ovaries before the age of natural menopause significantly increases the risk of cardiovascular disease (CVD) Menopause. 2007 May-Jun;14(3 Pt 2):562-6. Surgical menopause and cardiovascular risks. Lobo RA http://www.ncbi.nlm.nih.gov/ pubmed/17476145
20

The aim of this study was to determine the risk of metabolic syndrome in women who had undergone risk-reducing salpingo-oophorectomy (RRSO) because of increased risk of hereditary breast ovarian cancer (HBOC). A sample of 326 (65% of invited) women at risk of HBOC who had undergone RRSO was compared to 679 women from the general population. Mean follow-up after surgery was 6.5 years (standard deviations [SD] 4.4). RRSO was significantly associated with metabolic syndrome according to the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria (odds ratio [OR] 2.46 [95% confidence interval (CI) 1.63, 3.73]) and according to the International Diabetes Federation criteria (OR 2.49 [CI 1.60, 3.88]), as were increasing age and body mass index (BMI). RRSO in women at risk of HBOC is significantly associated with the metabolic syndrome, and the follow-up after RRSO should take these findings into consideration.

Methods 20,765 women aged 40–69 years were invited to a health study (HUNT-2 Norway 1995–97) and 17,650 (85%) attended. We compared 263 women with BOE before 50 years of age [63 with intact uterus (BO1 group), and 200 with hysterectomy also (BO2 group)] with 3 age-matched controls per case (n = 789). Data on demographic, somatic, mental, and lifestyle variables, physical measurements and blood tests were obtained. Results The BO1 and BO2 groups did not differ significantly regarding risk variables, and 4% had natural menopause. The combined BOE group had increased prevalence of MetS compared to controls according to the International Diabetes Federation's definition (47% versus 36%; p = .001) and the revised NCEP ATP III definition (35% versus 25%; p = .002), which remained after adjustments (for reproductive, global health, and lifestyle variables). The prevalence of Framingham risk score ≥ 10% was higher in cases (22%) versus controls (15%) p = .005. Conclusion The higher prevalence of MetS and increased Framingham risk scores in women with bilateral oophorectomy before 50 years of age suggests that these women may be at higher risk of type 2 diabetes and cardiovascular disease compared to their counterparts in the general population.

Gynecol Oncol. 2008 Jun;109(3):377-83. doi: 10.1016/j.ygyno.2008.02.025. Epub 2008 Apr 14. Bilateral oophorectomy before 50 years of age is significantly associated with the metabolic syndrome and Framingham risk score: a controlled, population-based study (HUNT-2). Dørum A1, Tonstad S, Liavaag AH, Michelsen TM, Hildrum B, Dahl AA.

http://www.ncbi.nlm.nih.gov/ pubmed/18407340

and

http://www.sciencedirect.com/science/article/pii/S0090825808001777

21 Due to an increased risk of cardiovascular disease, sexual dysfunction, hip fractures, and issues with cognitive function, women under 50 should be discouraged from electing to remove their ovaries J Womens Health (Larchmt). 2013 Sep;22(9):755-9. doi: 10.1089/jwh.2013.4259. Epub 2013 Jul 18. A critical evaluation of the evidence for ovarian conservation versus removal at the time of hysterectomy for benign disease. Matthews CA1 http://www.ncbi.nlm.nih.gov/ pubmed/23865788
22 Ovary removal may increase risk of glaucoma and estrogen replacement therapy does not seem to help Menopause. 2014 Apr;21(4):391-8. doi: 10.1097/GME.0b013e31829fd081. Risk of glaucoma after early bilateral oophorectomy. Vajaranant TS1, Grossardt BR, Maki PM, Pasquale LR, Sit AJ, Shuster LT, Rocca WA.

http://www.ncbi.nlm.nih.gov/ pubmed/24061049

23 Women whose ovaries are removed are at greater risk of osteoporosis (bone thinning) and arthritis. Women who take an estrogen replacement have some risk, women who do not have greater risk. McCarthy, AM. Bilateral Oophorectomy Is Associated with a Higher Prevalence of Arthritis and Lower Bone Mineral Density in Women 40 Years and Older. http://www.hopkinsmedicine. org/news/media/releases/ovary_ removal_in_younger_women_ linked_to_bone_thinning_and_ arthritis
24

Using National Hospital Discharge Survey data, an annual national representative survey of inpatient records - Hyster rate decreased from 5.4 per 1000 in 2000 to 5.1 per 1000 in 2004. Most common reason, 42% of time, was fibroids. Bilateral oophorectomies accompanied 54% of those hysterectomies. "Continued monitoring is needed to determine whether the observed trends persist and to evaluate impact on women's health. In the future, information on both inpatient and outpatient procedures may be important for hysterectomy surveillance."

DM note: As with my oophorectomy, they are not necessarily reported in patient billing, which is the source of these records, self-reported by the hospitals. Also, the majority of oophorectomies may be those that accompany outpatient procedures, which are not reported at all via this survey, but represent at least 40% of all hysterectomies each year.

Am J Obstet Gynecol. 2008 Jan;198(1):34.e1-7. Epub 2007 Nov 5. Inpatient hysterectomy surveillance in the United States, 2000-2004. Whiteman MK1, Hillis SD, Jamieson DJ, Morrow B, Podgornik MN, Brett KM, Marchbanks PA. http://www.ncbi.nlm.nih.gov/ pubmed/17981254/
25 Pre-menopausal women whose ovaries are removed are at a significantly increased risk of osteoporosis 3-6 years after surgery Br Med J. 1973 May 12; 2(5862): 325–328. PMCID: PMC1589320 Osteoporosis after Oophorectomy for Non-malignant Disease in Pre-menopausal Women J. M. Aitken, D. M. Hart, J. B. Anderson, R. Lindsay, D. A. Smith, and C. F. Speirs http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC1589320/
26 Women who experienced more frequent hot flashes (vasomotor symptoms) have increased risk for atherosclerosis, elevated blood pressure, insulin resistance, and possibly cardiovascular risk. Dr. Thurston and Dr. Barnabei. North American Menopause Society (NAMS) 23rd Annual Meeting: Abstract S-24. Presented October 5, 2012 http://www.medscape.com/ viewarticle/772465
27 Women younger than 65 clearly benefit from ovarian conservation and at no age is there a clear benefit from oophorectomy. Ovary removal increases the risk of dying from coronary heart disease, after age 65, from hip fracture. Ovary removal after age 50 resulted in a 40% increase in a first heart attack.

Ovarian Conservation at the Time of Hysterectomy for Benign Disease William H. Parker, MD , Michael S. Broder, MD , MPH , Zhimei Liu, PhD , Donna Shoupe, MD , Cindy Farquhar, MD , and Jonathan S. Berek, MD , MMSc
VOL. 106, NO. 2, AUGUST 2005 OBSTETRICS & GYNECOLOGY

http://www.researchgate.net/ profile/Cindy_Farquhar/ publication/6318523_Ovarian_ conservation_at_the_time_of_ hysterectomy_for_benign_ disease/links/ 09e41509b74fe2fa9f000000.pdf

28 Ovaries continue to produce hormones for many years after menopause. Women with ovaries removed have significantly lower levels of testosterone, androstenedione, estrone, and estradiol. J Clin Endocrinol Metab. 2007 Aug;92(8):3040-3. Epub 2007 May 22. Ovarian androgen production in postmenopausal women. Fogle RH1, Stanczyk FZ, Zhang X, Paulson RJ. http://www.ncbi.nlm.nih.gov/ pubmed/17519304
https://www. fertilityauthority.com/sites/ default/files/Ovarian_ androgen_production.pdf
29 Post-menopausal ovaries are a significant source of potent hormones (testosterone and androstenedione) that can convert (aromatase) to estrogen (E1 and E2). These hormone levels decrease by half when ovaries are removed. Gynecol Oncol. 1991 Jan;40(1):42-5. Reproductive hormone levels in gynecologic oncology patients undergoing surgical castration after spontaneous menopause. Hughes CL Jr1, Wall LL, Creasman WT. http://www.ncbi.nlm.nih.gov/ pubmed/1824939
30 Estrogen in post-menopausal women comes mostly from conversion of ovarian and adrenal androgens (testosterone and androstenedione). The ovary still produces androgens. The post-menop ovary is a potential source of estrogen and progesterone. Maturitas. 1984 Jul;6(1):45-53. Ovarian and peripheral plasma levels of progestogens, androgens and oestrogens in post-menopausal women. Lucisano A, Acampora MG, Russo N, Maniccia E, Montemurro A, Dell'Acqua S. http://www.ncbi.nlm.nih.gov/ pubmed/6472127
31 Women at age 55 who had had their ovaries removed had significantly lower bound and free testosterone than women who still had their ovaries and had gone through menopause. J Clin Endocrinol Metab. 2005 Jul;90(7):3847-53. Epub 2005 Apr 12. Androgen levels in adult females: changes with age, menopause, and oophorectomy. Davison SL1, Bell R, Donath S, Montalto JG, Davis SR. http://www.ncbi.nlm.nih.gov/ pubmed/15827095
32 Estrogen supplementation reduces DHEAS 23% and testosterone 42%. Obstet Gynecol. 1997 Dec;90(6):995-8. Effect of postmenopausal estrogen replacement on circulating androgens. Casson PR1, Elkind-Hirsch KE, Buster JE, Hornsby PJ, Carson SA, Snabes MC. http://www.ncbi.nlm.nih.gov/ pubmed/9397118
33 Estrogen is created by DHEA after menopause. Women with no ovaries produce 23% less DHEA than women who have them. Ovaries may not directly produce estrogens or androgens. The low DHEA in women with no ovaries may explain the high risk of coronary heart disease. Menopause. 2011 Jan;18(1):30-43. doi: 10.1097/gme.0b013e3181e195a6. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary? Labrie F1, Martel C, Balser J. http://www.ncbi.nlm.nih.gov/ pubmed/20683211
34 Ovarian hormones protect against development of atherosclerosis. Hysterectomy without BSO did not have any similar effect. Though Colditz / ARIC analysis found hormone therapy may reduce risk, it didn't take years since surgery into account. Dwyer study's use of a number of years since oophorectomy was the key to determining that there was a significant link. Even thought 90% women in this study had used hormone therapy (HRT), they demonstrated increased risk of atherosclerosis and CVD. This conflicts with Parker study. Study used very precise IMT measurements. Endogenous hormones play a role exogenous do not. HDL was specifically impacted. Am J Epidemiol. 2002 Sep 1;156(5):438-44. Carotid wall thickness and years since bilateral oophorectomy: the Los Angeles Atherosclerosis Study. Dwyer KM1, Nordstrom CK, Bairey Merz CN, Dwyer JH. http://aje.oxfordjournals.org/content/156/5/438.full
35 Women who had their ovaries removed before natural menopause were at an increased risk for Parkinson's disease and cognitive impairment. The risk increases the younger the patient is at time of surgery. 2.5x at age 28, 1.5x at age 45 for Parkinson's. 2.8x at age 38, 1.2 at age 45 for cognitive impairment. Estrogen may help, or the absence of progesterone or testosterone, or the disruption of the HPG axis may be the cause. Neurodegener Dis. 2008 Mar; 5(3-4): 257–260. Published online 2008 Mar 6. doi: 10.1159/000113718 PMCID: PMC2768565 NIHMSID: NIHMS137300 The Long-Term Effects of Oophorectomy on Cognitive and Motor Aging Are Age Dependent Walter A. Rocca,a,c,* Brandon R. Grossardt,b and Demetrius M. Maraganorec http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2768565/
36 Using Nurses' Health Study data of 29,380 women who had hysterectomy for a benign cause with both ovaries removed (bilateral oophorectomy) to women who did not, and adjusting for risk factors, overall mortality, fatal and non-fatal coronary heart disease, stroke, lung cancer, total all-cause cancer mortality risk increased. Compared to women who kept ovaries after surgery, an extra 1 in 9 who had ovaries removed would die in the 35 year avg life span after surgery. In no analysis or age group was ovary removal associated with increased survival. Obstet Gynecol. Author manuscript; available in PMC 2013 Oct 7. Published in final edited form as: Obstet Gynecol. 2009 May; 113(5): 1027–1037. doi: 10.1097/AOG.0b013e3181a11c64 PMCID: PMC3791619 NIHMSID: NIHMS181029 Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses’ Health Study William H. Parker, MD,1 Michael S. Broder, MD, MPH,2,3 Eunice Chang, PhD.,3 Diane Feskanich, ScD,4 Cindy Farquhar, MD,5 Zhimae Liu, PhD.,6 Donna Shoupe, MD,7 Jonathan S. Berek, MD, MMS,8 Susan Hankinson, ScD,4,9 and JoAnn E. Manson, MD, DrPH http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3791619/
37 About 600,000 women in the US have an inpatient hysterectomy each year. At least 20M women in the US have had a hysterectomy at any given time. Average 55% have ovaries removed at same time, at ages 15-44, rate is 40%, ages 45-54, rate is 75%. Hysterectomy Surveillance --- United States, 1994--1999 Homa Keshavarz, M.D.1,2 Susan D. Hillis, Ph.D.1 Burney A. Kieke1 Polly A. Marchbanks, Ph.D.1 1Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion 2Epidemic Intelligence Service Program, Epidemiology Program Office http://www.cdc.gov/mmwr/ preview/mmwrhtml/ss5105a1.htm
38 Operations on the reproductive organs were the one of top most common surgeries for women in the US (not including childbirth), second only to digestive disorders and cardiovascular surgery, in 2006 U.S. Department of Health and Human Services, Health Resources and Services Administration. Women's Health USA 2008. Rockville, Maryland: U.S. Department of Health and Human Services, 2008. http://mchb.hrsa.gov/ publications/pdfs/ womenhealth2008.pdf
39 In 2006, 40% of women 45-54 had had a hysterectomy U.S. Department of Health and Human Services, Health Resources and Services Administration. Women's Health USA 2008. Rockville, Maryland: U.S. Department of Health and Human Services, 2008. http://mchb.hrsa.gov/ publications/pdfs/ womenhealth2008.pdf
40 Of over 21,000 women diagnosed with ovarian cancer, 15,520 would die in 2006. Of over 40,000 women diagnosed with uterine cancer, 7,740 would die in 2006. U.S. Department of Health and Human Services, Health Resources and Services Administration. Women's Health USA 2008. Rockville, Maryland: U.S. Department of Health and Human Services, 2008. http://mchb.hrsa.gov/ publications/pdfs/ womenhealth2008.pdf
41 Hysterectomy is second most common surgery for women in the US, second only to c-section Office on Women’s Health in the Department of Health and Human Services, Sept. 2014 http://womenshealth.gov/ publications/our-publications/ fact-sheet/hysterectomy.html
42

Women with an average risk (low risk) of ovarian cancer should retain their ovaries until at least age 65 to benefit long-term survival

Should the ovaries be removed or retained at the time of hysterectomy for benign disease? M. Hickey 1 , M. Ambekar, and I. Hammond School of Women’s and Infants’ Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia, 2009
and
Curr Opin Obstet Gynecol. 2007 Aug;19(4):350-4. Elective oophorectomy in the gynecological patient: when is it desirable? Parker WH1, Shoupe D, Broder MS, Liu Z, Farquhar C, Berek JS.
http://humupd.oxfordjournals. org/content/16/2/131.long
and
http://www.ncbi.nlm.nih.gov/ pubmed/17625417?dopt=Abstract
43 Regardless of smoking history, women who've had their ovaries removed are at an almost doubled (1.92x) risk of lung cancer than those who haven't. Koushik A, Parent ME, Siemiatycki J, et al. Characteristics of menstruation and pregnancy and the risk of lung cancer in women. International Journal of Cancer 2009; Epub ahead of print on May 11. http://onlinelibrary.wiley. com/doi/10.1002/ijc.24560/ abstract
44 Women whose ovaries were removed before age 43 had a significantly increased risk of glaucoma (1.6x) Menopause. 2014 Apr;21(4):391-8. doi: 10.1097/GME.0b013e31829fd081. Risk of glaucoma after early bilateral oophorectomy. Vajaranant TS1, Grossardt BR, Maki PM, Pasquale LR, Sit AJ, Shuster LT, Rocca WA. http://www.ncbi.nlm.nih.gov/ pubmed/24061049
45 Activin tied to wound healing and lung health, prevention of arthritis and atherosclerosis (artery hardening) May 12, 2011; Blood: 117 (19) IMMUNOBIOLOGY The yin and yang of Activin A Silvano Sozzani and Tiziana Musso
and
Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia Bethany A. Cruise, Pin Xu, Alison K. Hall
http://www.bloodjournal.org/ content/117/19/5013?
and
http://www.sciencedirect.com/ science/article/pii/ S0012160604002465
46 Diabetes - women with hysterectomy concomitant with BSO (both ovaries removed) may represent a unique population with elevated risk for diabetes and other chronic diseases. Therefore the decision to remove the ovaries at the time of hysterectomy for benign conditions during the pre-menopausal years should be balanced with the risk of diabetes and its potential complications. BILATERAL OOPHORECTOMY AND THE RISK OF INCIDENT DIABETES IN POSTMENOPAUSAL WOMEN Authors and affiliations Duke Appiah PhD MPH 1 Stephen J. Winters MD 2 and Carlton A. Hornung PHD MPH. 1 1 Department of Epidemiology and Population Health, and 2 Division of Endocrinology, Metabolism and Diabetes, University of Louisville, Louisville, KY 40202 http://care.diabetesjournals. org/content/early/2013/11/05/ dc13-1986.full.pdf
47 Women with ovaries removed may have greater risk of issues with glucose metabolism (diabetes) than women who go through menopause. PHYS IOLOGICAL RESEARCH • ISSN 0862-8408 (print) • ISSN 1802-9973 (online) 2 014 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic Fax +420 241 062 164, e-mail: physres@biomed.cas.cz, www.biomed.cas.cz/physiolres Phys iol. Res. 63 (Suppl. 3): S395-S402, 2014 Bilat eral Oophorectomy May Have an Unfavorable Effect on Glucose Metabolism Compared With Natural Menopause M . LEJSKOVÁ 1,3 , J. PI Ť HA 2 , S. ADÁMKOVÁ 2 , O. AUZKÝ 2 , T. ADÁMEK 1 , E. BABKOVÁ 1 , V. LÁNSKÁ 2 , Š. ALUŠÍK 3 1 Department of Internal Medicine, Thomayer Hospital, Prague, Czech Republic, 2 Institute for Clinical and Experimental Me dicine, Prague, Czech Republic, 3 Institute for Postgraduate Medical Education, Prague, Czech Republic http://www.biomed.cas.cz/ physiolres/pdf/63%20Suppl%203/ 63_S395.pdf
48 Loss of ovarian function before natural menopause results in a disruption of the endocrine system. Ovary removal performed before the onset of menopause is associated with an increased risk of cognitive impairment or dementia. Ovary removal before the onset of menopause is associated with an increased risk of parkinsonism and Parkinson’s disease. Ovary removal performed before the onset of menopause is associated with an increased risk of long-term depressive and anxiety symptoms. The only impairments potentially helped by estrogen therapy are the risk of cognitive impairment and dementia if therapy is used leading up to age 50. Womens Health (Lond Engl). 2009 Jan; 5(1): 39–48. doi: 10.2217/17455057.5.1.39 PMCID: PMC2716666 NIHMSID: NIHMS88778 Long-term effects of bilateral oophorectomy on brain aging: Unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging W A Rocca,† L T Shuster, B R Grossardt, D M Maraganore, B S Gostout, Y E Geda, and L J Melton, III http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2716666/
49

Data from study analyzed 684 women who were intact, had hysterectomy, and had hyster + bilateral oophorectomy. 33% of women in study who reported just a hysterectomy didn't know their ovaries had also been removed. Estrone and estradiol levels in all women were about the same, suggesting that aromatase of androgens in tissue continues unaffected. SHBG increases 30% as intact women age, not easily explained. Doesn't occur in oophorectomized women. Androgens work with estrogens to relieve vasomotor (hot flashes) symptoms, increase density, libido, well-being, and energy. Androstenedione was down 15% and testosterone was down 40% in women with no ovaries.

Most importantly, though testosterone for women at natural menopause was low, it increased over time after menopause until a woman's 70s when it was at pre-menopausal levels again, whereas a woman with ovaries removed was always at a 40-50% deficiency vs premenopausal levels.


Removing ovaries when cancer isn't present should be reconsidered, and the replacement of missing androgens (androstenedione and testosterone) requires more study.

Hysterectomy, Oophorectomy, and Endogenous Sex Hormone Levels in Older Women: The Rancho Bernardo Study Gail A. Laughlin, Elizabeth Barrett-Connor, Donna Kritz-Silverstein, and Denise von Mühlen Address all correspondence and requests for reprints to: Dr. Elizabeth Barrett-Connor, Department of Family and Preventive Medicine, Division of Epidemiology, University of California-San Diego School of Medicine, La Jolla, California 92093-0607. DOI: http://dx.doi.org/10.1210/jcem.85.2.6405 Received: July 21, 1999 Accepted: November 10, 1999 Published Online: July 01, 2013 http://www.ncbi.nlm.nih.gov/ pubmed/10690870/
50 Study of 3,000 women tied low testosterone to increased all-cause mortality and incidence of cardiovascular events independent of traditional risk factors. Eur J Endocrinol. 2010 Oct;163(4):699-708. doi: 10.1530/EJE-10-0307. Epub 2010 Aug 4. Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients. Sievers C1, Klotsche J, Pieper L, Schneider HJ, März W, Wittchen HU, Stalla GK, Mantzoros C. http://www.ncbi.nlm.nih.gov/ pubmed/20685832
51 Symptoms of low testosterone and other androgens in women include loss of libido and decreased sexual motivation, arousal, fantasy, and enjoyment. Other nonsexual symptoms include loss of motivation, insomnia, depression, headache, loss of sense of well-being, fatigue, poor concentration, increased fat, and decreased lean body mass in conjunction with osteopenia or osteoporosis. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause AACE Menopause Guidelines Revision Task Force Endocr Pract. 2006;12(3):315-337.
and
Fertil Steril. 2002 Apr;77 Suppl 4:S72-6. The hypoandrogenic woman: pathophysiologic overview. Bachmann GA1.
http://www.medscape.com/ viewarticle/540531_12
and
http://www.ncbi.nlm.nih.gov/ pubmed/12007907
52 FSH and LH gonadotropins (hormones produced by the pituitary gland in the brain to stimulate hormone production in the ovaries) increased constantly after ovary removal surgery. See 53. Hum Reprod. 1995 Sep;10(9):2277-9. Gonadotrophins and prolactin rise after bilateral oophorectomy for benign conditions. Crosignani PG1, Meschia M, Bruschi F, Amicarelli F, Parazzini F. http://www.ncbi.nlm.nih.gov/ pubmed/8530651
53 Increased levels of LH (luteinizing hormone and FSH go up considerably when ovaries are removed) gonadotropin is linked to the presence of Alzheimer's. Clin Med Res. 2007 Oct; 5(3): 177–183. doi: 10.3121/cmr.2007.741 PMCID: PMC2111407 The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis Kate M. Webber, PhD, George Perry, PhD, Mark A. Smith, PhD, and Gemma Casadesus, PhD http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2111407/
54 Unlike DHEAS, made in the adrenal glands, ovary removal is associated with decreased estradiol (E2 estrogen), estrone (E1 estrogen), prolactin, SHBG, androstenedione, and testosterone. With hormone replacement therapy, E1, E2, and SHBG levels increased, but testosterone and androstenedione levels did not. Maturitas. 1993 Sep;17(2):101-11. Effects of oophorectomy and hormone replacement therapy on pituitary-gonadal function. Castelo-Branco C1, Martínez de Osaba MJ, Vanrezc JA, Fortuny A, González-Merlo J. http://www.ncbi.nlm.nih.gov/ pubmed/8231902
55 Levels of inhibin B hormone can accurately predict how much time until a woman enters menopause Predicting the menopause: the role of inhibin B, Professor Richard A. Anderson, MB ChB, MRCOG, Professor of Clinical Reproductive Science, Queen’s Medical Research Institute, University of Edinburgh; Consultant in Obstetrics & Gynaecology, Edinburgh Royal Infirmary., 2007 http://onlinelibrary.wiley. com/store/10.1002/tre.10/ asset/10_ftp.pdf;jsessionid= C8317C0E6E88D5EC859313A9F21CCD AC.f03t02?v=1&t=i9hh59i9&s= 647d73e8ca1efa5636b0d9f8e69560 91fa5c555d
56 Manipulation of the gonads (ovaries/testes) and their role in the hypothalamic-pituitary-gonadal axis (biochemical conversation with the brain) has an effect on the adrenal glands and their role in the hypothalamic-pituitary-adrenal axis. Both play a role in psychiatric, cardiovascular and metabolic disease, make many of the same steroid hormones, and are interdependent. Adrenal glands are a front line of defense against stress. J Neuroendocrinol. 2002 Jun;14(6):506-13. Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes. Viau V1. http://www.ncbi.nlm.nih.gov/ pubmed/12047726
57 ACOG Practice Bulletin 89, 2008, states Women with family histories suggestive of BRCA1 and BRCA2 mutations should be referred for genetic counseling and evaluation for BRCA testing. For women with an increased risk of ovarian cancer, risk-reducing salpingo-oophorectomy should include careful inspection of the peritoneal cavity, pelvic washings, removal of the fallopian tubes, and ligation of the ovarian vessels at the pelvic brim. Strong consideration should be made for retaining normal ovaries in pre-menopausal women who are not at increased genetic risk of ovarian cancer. Given the risk of ovarian cancer in postmenopausal women, ovarian removal at the time of hysterectomy should be considered for these women. Women with endometriosis, pelvic inflammatory disease, and chronic pelvic pain are at higher risk of re-operation; consequently, the risk of subsequent ovarian surgery if the ovaries are retained should be weighed against the benefit of ovarian retention in these patients.

ACOG Practice Bulletin, 2008

http://journals.lww.com/ greenjournal/Citation/2008/ 01000/ACOG_Practice_Bulletin_ No__89__Elective_and.39.aspx
and
http://www.guideline.gov/ content.aspx?id=12190
58 Conserving the ovaries, rather than removing them, during hysterectomy is associated with a lower risk of coronary heart disease and both all-cause and cancer-related mortality. J Fam Pract. 2009 Sep; 58(9): 478–480. PMCID: PMC3183929 Ovary-sparing hysterectomy: Is it right for your patient? Umang Sharma, MDcorresponding author and Sarah-Anne Schumann, MD http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3183929/
59 89% of hysterectomies were for benign conditions/not related to malignancies Obstet Gynecol. 2007 Nov;110(5):1091-5. Hysterectomy rates in the United States, 2003. Wu JM1, Wechter ME, Geller EJ, Nguyen TV, Visco AG. http://www.ncbi.nlm.nih.gov/ pubmed/17978124/
60 FDA warns that testosterone supplements can increase the risk of blood clots FDA.gov, FDA adding general warning to testosterone products about potential for venous blood clots http://www.fda.gov/Drugs/ DrugSafety/ucm401746.htm
61 Endometriosis: My data about endometriosis comes from this source Women's Surgery Group - Endometriosis Myths http://www.womenssurgerygroup. com/conditions/endometriosis/ myths.asp
62 Hot flashes worse in women who've had their ovaries removed than in those who haven't Breast Cancer Res Treat. 1999 Dec;58(3):281-6. Symptoms associated with oophorectomy and tamoxifen treatment for breast cancer in pre-menopausal Vietnamese women. Love RR1, Nguyen BD, Nguyen CB, Nguyen VD, Havighurst TC. http://www.ncbi.nlm.nih.gov/ pubmed/10718489
63 Racial differences in ovarian cancer risk J Natl Med Assoc. 2000 Apr; 92(4): 176–182. PMCID: PMC2640605 Racial differences in ovarian cancer risk. R. B. Ness, J. A. Grisso, J. Klapper, and R. Vergona
and
CDC: Ovarian Cancer Rates by Race and Ethnicity
http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2640605/
and
http://www.cdc.gov/cancer/ ovarian/statistics/race.htm
64 Morcellation: Of the 232,882 women who underwent minimally invasive hysterectomy, morcellation was done for 15% of cases. Among the women who had morcellation, there were 99 cases of uterine cancer (0.27 percent; 1 in 370); 39 uterine neoplasms of uncertain malignant potential; 368 cases of endometrial hyperplasia; and 26 other gynecologic malignancies.
The prevalence of malignancy was 0.34 percent and of all neoplastic conditions was 1.5 percent.
Malignant disease was associated with increasing age; compared with women age 40 years, the prevalence ratios were: 50 to 54 years, 4.97; 55 to 59, 19.37; 60 to 64, 21.36; and ≥65, 35.97. In absolute numbers, the prevalence of cancer in this series for women under age 40 was 1/1500 and for women 40 to 44 was 1/1100.
JAMA. 2014 Sep 24;312(12):1253-5. doi: 10.1001/jama.2014.9005. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. Wright JD1, Tergas AI1, Burke WM1, Cui RR1, Ananth CV1, Chen L1, Hershman DL2. http://www.ncbi.nlm.nih.gov/ pubmed?term=25051495
65 BRCA 1 & 2 - risk decrease after ovary removal statistics Breastcancer.org: Is Prophylactic Ovary Removal Right for You? http://www.breastcancer.org/ treatment/surgery/ prophylactic_ovary/who_its_for
66 Tumor markers for ovarian cancer oncolink.org: OncoLink Team The Abramson Cancer Center of the University of Pennsylvania Last Modified: December 1, 2014

http://www.oncolink.org/types/ article.cfm?c=206&id=7143

67 It appears that some ovarian cancer starts not in the ovaries but in the fallopian tubes. Removing the tubes rather than the ovaries may result in a decreased cancer risk. Opportunistic salpingectomy for ovarian, fallopian tubal, and peritoneal carcinoma risk reduction Authors Dianne M Miller, MD, FRCSC Jessica N McAlpine, MD, FACOG, FRCPSC http://www.uptodate.com/ contents/opportunistic- salpingectomy-for-ovarian- fallopian-tubal-and- peritoneal-carcinoma-risk- reduction
and
https://www.sgo.org/clinical- practice/guidelines/sgo- clinical-practice-statement- salpingectomy-for-ovarian- cancer-prevention/
68 How many women in the US get and die of ovarian cancer each year cancer.org http://www.cancer.org/cancer/ ovariancancer/overviewguide/ ovarian-cancer-overview-key-st atistics
69 Heart disease rates in women compared to cancer rates heartfoundation.org http://www.theheartfoundation. org/heart-disease-facts/heart- disease-statistics
70 AJOG: “Numerous studies link bilateral oophorectomy [removal of both ovaries] to an increased risk of cardiovascular disease in both premenopausal and post-menopausal women.”

Prophylactic bilateral oophorectomy or removal of remaining ovary at the time of hysterectomy in the United States, 1979-2004 Presented orally at the 29th Scientific Meeting of the American Urogynecologic Society, Chicago, IL, Sept. 4-6, 2008. Jerry L. Lowder, MD, MSc , Sallie S. Oliphant, MD , Chiara Ghetti, MD , Lara J. Burrows, MD, MSc , Leslie A. Meyn, MS , Judith Balk, MD Received: May 29, 2009; Received in revised form: September 24, 2009; Accepted: November 18, 2009; Published Online: January 08, 2010
American Journal of Obstetrics & Gynecology, JUNE 2010

http://www.ajog.org/article/ S0002-9378%2809%2902204-2/ pdfSummary

71 Hormone (estrogen and androgen) levels in women before and after menopause, as well as without ovaries Endocrinology of the menopause Won-whe Kim Department of Obstetrics and Gynaecology, School of Medicine, Pusan National University, Pusan, Republic of Korea http://www.gfmer.ch/Books/ bookmp/33.htm
72 Average post-menopausal women gain between 2-5 pounds. Women who lose estradiol (E2 estrogen) lose subcutaneous fat (just under the skin) and gain the really unhealthy kind of fat, visceral fat, located around organs inside the abdomen and deeper than subcutaneous fat. Weight gain in the abdomen increases insulin resistance (diabetes). Excess fat also results in increased creation of E1estrone estrogen, the estrogen most closely tied to breast cancer. Estrogen replacement is tied to a reduction in diabetes. Weight Gain in Menopause By Paul Hueseman, PharmD July 2006 http://www.project-aware.org/ Resource/articlearchives/weigh tgain.shtml
73 Women who had their ovaries removed due to BRCA 1 or 2 reported: 73% of patients reported sexual dysfunction, such as the absence of satisfaction and presence of pain; 61% had problems sleeping (insomnia); 57% had symptoms of menopause such as hot flashes (vasomotor) and vaginal dryness; and 56% had elevated levels of stress (cortisol, adrenal glands, HPA axis). Hormone replacement therapy did help mitigate symptoms, particularly in women with no cancer history who underwent oophorectomy prior to age 50. These adverse effects highlight the need for better alternatives for prevention than ovary removal. Domchek SM, Li J, Digiovanni L, et al: Quality of life in BRCA1 and BRCA2 mutation carriers following risk-reducing salpingo-oophorectomy. Abstract 1508. Presented at the 2014 ASCO Annual Meeting, May 31, 2014. http://www.ascopost.com/ issues/july-25,-2014/women- with-brca-mutations-report- significant-side-effects- following-risk-reducing- salpingo-oophorectomy.aspx
74 Fibroids and fibroid symptoms Mayo Clinic's site, Penn State site http://www.mayoclinic.org/ diseases-conditions/uterine- fibroids/basics/definition/ con-20037901and
http://pennstatehershey.adam. com/content.aspx?productId=10& pid=10&gid=000073
75 An LDH blood test and an MRI alleged to determine if a mass is a fibroid or sarcoma (cancer) with very reliable accuracy Differentiating uterine leiomyomas (fibroids) from uterine sarcomas Author Elizabeth A Stewart, MD, Aug 2014
and
Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus A. Goto1, S. Takeuchi3, K. Sugimura2 andT. Maruo1 Article first published online: 1 AUG 2002
http://www.uptodate.com/ contents/differentiating- uterine-leiomyomas-fibroids- from-uterine-sarcomas
and
http://onlinelibrary.wiley. com/doi/10.1046/j.1525-1438. 2002.01086.x/abstract
76 Particularly unhealthy (visceral) type of fat is associated in women with diminished levels of SHBG and natural E2 (estradiol) to testosterone ratio, and to elevated levels of free T after adjustment for age and total fat mass. Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy. R Leenen, K van der Kooy, J C Seidell, P Deurenberg, and H P Koppeschaar DOI: http://dx.doi.org/10.1210/ jcem.78.6.8200956 Published Online: July 01, 2013 http://press.endocrine.org/ doi/abs/10.1210/jcem.78.6. 8200956
77 Incontinence - doubled risk after hysterectomy Aging Health Long-term Effects of Hysterectomy A Focus on the Aging Patient Catharina Forsgren, Daniel Altman, Aging Health. 2013;9(2):179-187. http://www.medscape.com/ viewarticle/805517
78 Higher risk of incontinence after vaginal hysterectomy Int Urogynecol J. 2011 Sep; 22(9): 1179–1184. Published online 2011 Apr 12. doi: 10.1007/s00192-011-1427-y PMCID: PMC3162140 Predicting the development of stress urinary incontinence 3 years after hysterectomy Mariëlle M. E. Lakeman,corresponding author1 C. Huub Van Der Vaart,2 Jan Willem Van Der Steeg,1 Jan-Paul W. R. Roovers,1 and On behalf of the HysVA study group http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3162140/
79 Are there any risks - oophorectomy limited info Illinois Dept of Public Health Hysterectomy info

http://www.idph.state.il.us/ about/womenshealth/factsheets/ hyster.htm

80 Though ovaries are removed or fail 73% of the time at hysterectomy, there is controversy over whether castration should be used alongside hysterectomy. Of the 90% hysterectomies for benign conditions, 35% fibroids, 30% heavy bleeding, 25% endometriosis. HERS foundation calls hyst tantamount to castration. Yale Medical responds. Time magazine: Are Hysterectomies Too Common? By Coco Masters Tuesday, July 17, 2007 http://content.time.com/time/ health/article/0,8599,1644050, 00.html?cnn=yes
81 90% of hysterectomies are for benign conditions. 35% are for fibroids Brigham & Womens Hospital: Hysterectomy Options http://www.brighamandwomens. org/Departments_and_Services/ obgyn/services/mininvgynsurg/ mininvoptions/hysterectomy. aspx
82

"Study"
Sarrel, Researchers at Yale University say nearly 50,000 women may have died prematurely after they stopped taking hormone-replacement therapy (HRT) to treat menopause symptoms, following a much publicized 2002 study that revealed the treatment increased risk of heart disease and breast cancer.

Researchers at Yale University say nearly 50,000 women may have died prematurely after they stopped taking hormone-replacement therapy (HRT) to treat menopause symptoms, following a much publicized 2002 study that revealed the treatment increased risk of heart disease and breast cancer.

No mention of who paid for the study.

Time magazine: Hormone-Replacement Therapy: Could Estrogen Have Saved 50,000 Lives? By Alexandra Sifferlin http://content.time.com/time/ health/article/0,8599,1644050, 00.html?cnn=yes
83 Role of oophorectomy in high blood pressure Maturitas. 2004 Feb 20;47(2):131-8. Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis. Mercuro G1, Zoncu S, Saiu F, Mascia M, Melis GB, Rosano GM. http://www.ncbi.nlm.nih.gov/ pubmed/14757272
84 8% fewer women make it to age 80 if they've had their ovaries removed between ages 50-54 during hysterectomy, and 4% fewer if ovaries removed between 55-59. The increased mortality for women at average risk of ovarian cancer, for those who keep their ovaries, is less than half of 1% (.47%). Menopause. 2007 May-Jun;14(3 Pt 2):580-5. Elective oophorectomy for benign gynecological disorders. Shoupe D1, Parker WH, Broder MS, Liu Z, Farquhar C, Berek JS. http://www.ncbi.nlm.nih.gov/ pubmed/17476148
85 Hysterectomy decreases ovarian blood supply and function

Climacteric. 2006 Aug;9(4):283-9. The effect of hysterectomy on ovarian blood supply and endocrine function. Xiangying H1, Lili H, Yifu S.
and
Ultrasound Med. 2005 Feb;24(2):169-74. Effect of total abdominal hysterectomy on ovarian blood supply in women of reproductive age. Petri Nahás EA1, Pontes A, Nahas-Neto J, Borges VT, Dias R, Traiman P.

http://www.ncbi.nlm.nih.gov/ pubmed/16857658
and
http://www.ncbi.nlm.nih.gov/ pubmed/15661947
86 Ovaries fail about 50% of the time within 5 years of hysterectomy Dorie Eldridge, Hysterectomy Toolbox http://hyst.blogspot.com/2004/ 09/ovarian-failure-following- hysterectomy.html
87 1 in 3 women in the US has had a hysterectomy by age 60 American Congress of Obstetricians & Gynecologists http://www.acog.org/-/media/ NewsRoom/MediaKit.pdf
88 52% of hysterectomies were performed on women under age 44. 40% of women 45-54 has had a hysterectomy. 75% of women 45-54 have ovaries removed at the same time. 40% of women 15-44 have ovaries removed at hysterectomy. Hysterectomy Surveillance --- United States, 1994--1999 Homa Keshavarz, M.D.1,2 Susan D. Hillis, Ph.D.1 Burney A. Kieke1 Polly A. Marchbanks, Ph.D.1 1Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion 2Epidemic Intelligence Service Program, Epidemiology Program Office http://www.cdc.gov/mmwr/ preview/mmwrhtml/ss5105a1.htm
89 Insufficient testosterone levels in women creates complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure Sex Health. 2006 May;3(2):73-8. A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire. Burger HG1, Papalia MA. http://www.ncbi.nlm.nih.gov/ pubmed/16800391
90 Skin thickness and water retention affected by levels of estrogen and progesterone Br J Dermatol. 1998 Sep;139(3):462-7. The influence of female sex hormones on skin thickness: evaluation using 20 MHz sonography. Eisenbeiss C1, Welzel J, Schmeller W. http://www.ncbi.nlm.nih.gov/ pubmed/9767291/
91 Estrogen affects all aspects of skin appearance and behavior Expert Opin Ther Targets. 2005 Jun;9(3):617-29. Oestrogen functions in skin and skin appendages. Thornton MJ1. http://www.ncbi.nlm.nih.gov/ pubmed/15948678/
92 Ovaries almost twice as likely to fail after hysterectomy Obstet Gynecol. Author manuscript; available in PMC 2012 Dec 1. Published in final edited form as: Obstet Gynecol. 2011 Dec; 118(6): 1271–1279. doi: 10.1097/AOG.0b013e318236fd12 PMCID: PMC3223258 NIHMSID: NIHMS330938 Effect of Hysterectomy With Ovarian Preservation on Ovarian Function Patricia G. Moorman, Ph.D.,1 Evan R. Myers, M.D., M.P.H.,2 Joellen M. Schildkraut, Ph.D.,1 Edwin S. Iversen, Ph.D.,3 Frances Wang, M.S.,1 and Nicolette Warren, M.S.1 http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3223258/
93 FDA says they estimate that approximately 1 in 352 women undergoing hysterectomy or myomectomy for the treatment of fibroids is found to have an unsuspected uterine sarcoma, so the risk that that cancer will be upstaged by chopped up tissue is great enough to label morcellators (that chop up the parts they're removing to be removed through small holes in the abdomen) with two warnings. UPDATED Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication http://www.fda.gov/ MedicalDevices/Safety/ AlertsandNotices/ucm424443.htm
94 Risk of fibroid recurrence, fibroid treatments Dr. William H. Parker's website http://www. fibroidsecondopinion.com/2011/ 12/risk-of-fibroid-recurrence- following-myomectomy/
95 Adenomyosis definition and treatment Mayo Clinic site http://www.mayoclinic.org/ diseases-conditions/ adenomyosis/multimedia/ adenomyosis/img-20007089
96 Women and heart disease facts Women's Heart Foundation http://www.womensheart.org/ content/heartdisease/heart_ disease_facts.asp
97 Ovarian cancer statistics Cancer.net / American Cancer Society http://www.cancer.net/cancer- types/ovarian-cancer/ statistics
98 Prolapse after hysterectomy Australian Urology Associates website http://www.aua.com.au/content_ common/pg-femaleurology.seo
99 76% of hysterectomies in this study were recommended inappropriately Obstet Gynecol. 2000 Feb;95(2):199-205. The appropriateness of recommendations for hysterectomy. Broder MS1, Kanouse DE, Mittman BS, Bernstein SJ. http://www.ncbi.nlm.nih.gov/ pubmed/10674580
100 Gynecologists opinions on oophorectomy at time of hysterectomy; taking history into account; letting the patient choose. Alarming. 66% of gynecological surgeons who responded said they were willing to perform ovary removal on women in their 30s at the women’s request. And more than 75% of gynecologists who responded said they didn’t take a woman’s personal medical history into account when deciding whether to perform the surgery. Menopause. 2014 Apr;21(4):355-60. doi: 10.1097/GME.0b013e31829fc376. Obstetrician-gynecologists' opinions on elective bilateral oophorectomy at the time of hysterectomy in the United States: a nationwide survey. Harmanli O1, Shinnick J, Jones K, St Marie P.

http://www.ncbi.nlm.nih.gov/ pubmed/23942250
and
http://www.medscape.com/ viewarticle/824027

101 2% of women have family history of ovarian or breast cancer Bilateral oophorectomy: Solving the risk/benefit equation — Choosing candidates, monitoring outcomes Prophylactic bilateral oophorectomy at the time of hysterectomy confers long-term benefits for many women. July 01, 2011 By William H. Parker, MD http://contemporaryobgyn. modernmedicine.com/ contemporary-obgyn/news/ modernmedicine/modern- medicine-now/bilateral- oophorectomy-solving- riskbenefi?page=full
102 health outcomes appear 15 years later; for women up to age 65, ovarian conservation should be encouraged due to numerous health risks associated with ovary removal Prophylactic bilateral oophorectomy jeopardizes long-term health LYNNE T. SHUSTER, MD; BRANDON R. GROSSARDT, MS; BOBBIE S. GOSTOUT, MD; AND WALTER A. ROCCA, MD, MPH ‘Menopausal Medicine,’ VOLUME18, NUMBER4 — OCTOBER2010 http://www.reproductivefacts. org/uploadedFiles/ASRM_ Content/News_and_Publications/ Journals_and_Newsletters/ Menopausal_Medicine/2010/ MenMed_Final_October%202010. pdf
103 no reason to remove ovaries except cancer; ovaries still make hormones; removing ovaries leads to incr risk of osteoporosis, cardiovascular disease, brings on more severe symptoms than natural menopause Weill Medical at Cornell University, Women's Health Advisor, December 2001 http://www.womens-health- advisor.com/hysterectomy.html
104 ovary removal is associated with cognitive impairment and dementia Neurology. 2007 Sep 11;69(11):1074-83. Epub 2007 Aug 29. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Rocca WA1, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd. http://www.ncbi.nlm.nih.gov/ pubmed/17761551
105 Angelina Jolie's March 2015 op-ed piece in the New York Times about her ovary removal (oophorectomy) nytimes.com Angelina Jolie Pitt: Diary of a Surgery By ANGELINA JOLIE PITT MARCH 24, 2015 http://www.nytimes.com/2015/ 03/24/opinion/angelina-jolie- pitt-diary-of-a-surgery.html
106 Risks of progestins vs natural progesterone J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. Campagnoli C1, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F. http://www.ncbi.nlm.nih.gov/ pubmed/15908197
107 High cortisol and low testosterone are linked to insulin resistance syndrome and coronary heart disease / ischemic heart disease Coronary Heart Disease Cortisol, Testosterone, and Coronary Heart Disease Prospective Evidence From the Caerphilly Study George Davey Smith, DSc; Yoav Ben-Shlomo, BSc, MBBS, MRCP, FFPHM, PhD; Andrew Beswick, BSc; John Yarnell, MBChB, DPH, MSCM, MD, MFPHM (Ire), FFPHM; Stafford Lightman, MBChB, PhD, FMedSci; Peter Elwood, DSc, MD, FRCP, FFPHM http://circ.ahajournals.org/ content/112/3/332.full
108 Androgens contribute to the maintenance of normal ovarian function, bone metabolism, cognition, and sexual behavior. Premenop serum testosterone is 30-40 ng/dL, 20-30 ng/dL post-menopause; androstenedione produced in ovaries declines; ovarian production of testosterone remains stable in menopause. testosterone declines 40-50% in women with no ovaries vs post-menopausal women; DHEA and DHEAS also decline with age to half at menopause; DHEA supplement increases serum DHEAS and testosterone, but doesn't seem to improve low T symptoms. Don't use DHEA or A supplements. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause AACE Menopause Guidelines Revision Task Force Endocr Pract. 2006;12(3):315-337.
and
Fertil Steril. 2002 Apr;77 Suppl 4:S72-6. The hypoandrogenic woman: pathophysiologic overview. Bachmann GA1.
http://www.medscape.com/ viewarticle/540531_12
109 Relationship between cortisol and sleep, bone density. Hydrocortisone supplementation. Ther Adv Endocrinol Metab. 2010 Jun; 1(3): 129–138. doi: 10.1177/2042018810380214 PMCID: PMC3475279 Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy Sharon Chan and Miguel Debono http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3475279/
110 Depression in women linked to a dysfunction of the HPA axis and flatter daytime levels of cortisol peaks Biol Psychol. 2013 Apr; 93(1): 150–158. Published online 2013 Feb 11. doi: 10.1016/j.biopsycho.2013.01. 018 PMCID: PMC3687535 NIHMSID: NIHMS445370 Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder Michael R. Jarcho,a,* George M. Slavich,a Hana Tylova-Stein,b Owen M. Wolkowitz,b and Heather M. Burkeb http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3687535/
111 Documentation of the interaction among the thyroid, HPA/adrenal and HPG/gonadal axes Published online 2014 Aug 27. doi: 10.3389/fendo.2014.00139 PMCID: PMC4145579 Crossover of the Hypothalamic Pituitary–Adrenal/Interrenal, –Thyroid, and –Gonadal Axes in Testicular Development Diana C. Castañeda Cortés,1 Valerie S. Langlois,2,* and Juan I. Fernandino1,* http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC4145579/
112 Role of the HPA/adrenals in insomnia Published in final edited form as: Curr Psychiatry Rep. 2013 Dec; 15(12): 418. doi: 10.1007/s11920-013-0418-8 PMCID: PMC3972485 NIHMSID: NIHMS537826 Insomnia and Its Impact on Physical and Mental Health Julio Fernandez-Mendoza, PhD and Alexandros N. Vgontzas, MD http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3972485/
113 HPA activity, high cortisol and type II diabetes Diabetes Care. 2007 Jan;30(1):83-8. Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Chiodini I1, Adda G, Scillitani A, Coletti F, Morelli V, Di Lembo S, Epaminonda P, Masserini B, Beck-Peccoz P, Orsi E, Ambrosi B, Arosio M. http://www.ncbi.nlm.nih.gov/ pubmed/17192338
114 I don't use Wikipedia as a source, but the articles cited here are valid. Cortisol's role in bone, glucose, wound healing, bloating, stomach issues, memory, sleep, depression are cited here. cortisol section of wikipedia http://en.wikipedia.org/wiki/ Cortisol
115 A compromised endocrine system affects adrenal and thyroid function Indian J Endocrinol Metab. 2011 Jan-Mar; 15(1): 18–22. doi: 10.4103/2230-8210.77573 PMCID: PMC3079864 Stress and hormones Salam Ranabir and K. Reetu1 http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3079864/
116 Statistically significant gradients were seen between the ovarian venous and peripheral samples for T, A, DHEA, E1, and E2. Postoperative levels of T and E1, but not A, DHEA, or E2, were statistically significantly lower than preoperative levels. A gradient for T between the ovarian venous and peripheral blood was present in four of five women who were menopausal for more than 10 yr. testosterone down 42% androstenedione down 17% DHEA down 18% estrone (E1 estrogen) down 26% estradiol (E2 estrogen) down 8% Ovarian Androgen Production in Postmenopausal Women Robin H. Fogle, Frank Z. Stanczyk, Xiaohua Zhang, and Richard J. Paulson
0021-972X/07 The Journal of Clinical Endocrinology & Metabolism 92(8):3040–3043 Printed in U.S.A. Copyright © 2007 by The Endocrine Society doi: 10.1210/jc.2007-0581
https://www. fertilityauthority.com/sites/ default/files/Ovarian_ androgen_production.pdf
117 Adrenal cortex probably source of much post-menopausal E1, E2, Pg, and most important source of DHEA, but post-menopausal ovaries make 50% plasma testosterone and 30% androstenedione. hCG stimulation has little influence on ovarian steroid production. In women with no ovaries, T, A, DHT, and DHEA were all lower. J Clin Endocrinol Metab. 1976 Feb;42(2):247-53. The hormonal activity of the postmenopausal ovary. Vermeulen A. http://www.ncbi.nlm.nih.gov/ pubmed/177438
118 Studies dating to the 1970's confirming the production of androgens in the post-menopausal ovary Judd HL, Lucas WE, Yen SSC 1974 Effect of oophorectomy on circulating testosterone and androstenedione levels in patients with endometrial cancer. Am J Obstet Gynecol 118:793–798
and
Judd HL, Judd GE, Lucas WE, Yen SS 1974 Endocrine function of the post- menopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab 39:1020–1024

http://www.ncbi.nlm.nih.gov/ pubmed/4815860
and
http://www.ncbi.nlm.nih.gov/ pubmed/4430702


119 Low testosterone and decreased libido Womens Health (Lond Engl). 2006 May;2(3):459-77. doi: 10.2217/17455057.2.3.459. Testosterone and libido in surgically and naturally menopausal women. Alexander JL1, Dennerstein L, Burger H, Graziottin A. http://www.ncbi.nlm.nih.gov/ pubmed/19803917
120 Testosterone and libido in men J Clin Endocrinol Metab. 1992 Dec;75(6):1503-7. The effects of exogenous testosterone on sexuality and mood of normal men. Anderson RA1, Bancroft J, Wu FC. http://www.ncbi.nlm.nih.gov/ pubmed/1464655
121 Uncertain whether libido matters to women (duh), but if it does, testosterone patches help, but may be dangerous. Rev Obstet Gynecol. 2009 Winter; 2(1): 65–66. PMCID: PMC2673004 Testosterone and Sexual Desire Athol Kent, MBChB, MPhil, FRCOG http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2673004/
122 Testosterone therapy is absolutely linked to improved sexual desire. Prog Urol. 2013 Jul;23(9):621-8. doi: 10.1016/j.purol.2013.01.019. Epub 2013 Apr 4. [Hypoactive sexual desire and testosterone deficiency in men]. [Article in French] Lejeune H1, Huyghe É, Droupy S. http://www.ncbi.nlm.nih.gov/ pubmed/23830256
123 PremPro and WHI (Women's Health Initiative) women taking the combined HRT of synthetic estrogen and synthetic progesterone were 25 percent more likely to have an invasive breast cancer than women in the placebo group, 78 percent more likely to have cancer that had spread to the lymph nodes, and were almost twice as likely as the placebo group to die of breast cancer (and 57 percent more likely to die of other causes) FDA Statement on the Results of the Women's Health Initiative (Posted 8/13/2002) http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm135331.htm
124 Before menopause, women's ovaries contribute 60% of androstenedione, 20% DHEA, and 25-35% testosterone; the adrenal glands contribute 40% androstenedione, 50% DHEA, 90% DHEAS, and 25% of T. The rest of T is made from the conversion of adrenal androgens in other parts of the body. The ovaries make estrogen by converting T or DHEA to E's. Androgens in women, the Women’s Health Program, Monash University © October 2010. http://med.monash.edu.au/ sphpm/womenshealth/docs/ androgens-in-women.pdf
125

Feb 2004 letter from the National Heart, Lung, and Blood Institute to women who participated in the WHI (women's health initiative) estrogen-alone trial, stating that they were ending the study more than a year early due to health risks including an increased risk of stroke

Dept of Health and Human Services, NIH, NHLBI, Women's Health Initiative Letter to women participating in estrogen-alone drug study https://www.nhlbi.nih.gov/whi/e-a_letter.htm
126 Data out of the 2004 WHI estrogen-alone study indicates that .625 mg of equine estrogen (Premarin) supplement increased the risks in women aged 65-79 1.49x for dementia and 1.34x for cognitive impairment. June 23/30, 2004, Vol 291, No. 24 > < Previous Article Next Article > Original Contribution | June 23/30, 2004 Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal WomenWomen's Health Initiative Memory Study FREE Sally A. Shumaker, PhD; Claudine Legault, PhD; Lewis Kuller, MD, DrPH; Stephen R. Rapp, PhD; Leon Thal, MD; Dorothy S. Lane, MD, MPH; Howard Fillit, MD; Marcia L. Stefanick, PhD; Susan L. Hendrix, DO; Cora E. Lewis, MD; Kamal Masaki, MD; Laura H. Coker, PhD; for the Women's Health Initiative Memory Study http://jama.jamanetwork.com/article.aspx?articleid=198994
127 Data regarding the Premarin study. Coronary artery calcium, breast cancer risk, venous thrombosis, coronary heart disease, dementia and cognitive function. Dept of Health and Human Services, NIH, NHLBI, Women's Health Initiative informational page about the estrogen-alone drug study https://www.nhlbi.nih.gov/whi/estro_alone.htm
128 atherosclerosis, any mitigation by HRT in oophorectomy vs no oophorectomy. Carotid wall thickness and years since bilateral oophorectomy: the Los Angeles Atherosclerosis Study. Dwyer KM1, Nordstrom CK, Bairey Merz CN, Dwyer JH. Author information http://www.ncbi.nlm.nih.gov/pubmed/12196313
129 Definition of metabolic syndrome Mayo Clinic http://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/basics/definition/con-20027243
130 6.5 years after bilateral oophorectomy, this study proved that removal of the ovaries was significantly associated with metabolic syndrome (odds ratio 2.46, CI 95%) acc to National Cholesterol Educaiton Program Adult Treatment Panel III criteria and OR 2.49 acc to the Intl. Diabetes Federation criteria. (cohort - 1,000 women, 1/3 had ovaries removed) Eur J Cancer. 2009 Jan;45(1):82-9. doi: 10.1016/j.ejca.2008.09.028. Epub 2008 Nov 12. Metabolic syndrome after risk-reducing salpingo-oophorectomy in women at high risk for hereditary breast ovarian cancer: a controlled observational study. Michelsen TM1, Pripp AH, Tonstad S, Tropé CG, Dørum A. http://www.ncbi.nlm.nih.gov/pubmed/19008092
131 Elevated serum CA-125 and false positives for ovarian cancer J Obstet Gynaecol Can. 2004 Aug;26(8):717-28. Screening postmenopausal women for ovarian cancer: a systematic review. Fung MF1, Bryson P, Johnston M, Chambers A; Cancer Care Ontario Practice Guidelines Initiative Gynecology Cancer Disease Site Group. http://www.ncbi.nlm.nih.gov/pubmed/15307976
132 Aldosterone, cortisol and metabolic syndrome after oophorectomy Endocrinology: An Integrated Approach. Show details Nussey S, Whitehead S. Oxford: BIOS Scientific Publishers; 2001. Contents Search term Clear input http://www.ncbi.nlm.nih.gov/books/NBK26/
133 Dumbing down and rendering emotional a surgical decision for women Uterine Fibroids Health Center, WebMD http://www.webmd.com/women/uterine-fibroids/uterine-fibroids-topic-overview?page=2
134 Relative risks of different kinds of estrogen Cedars-Sinai, Study: Different Hormone Therapy Formulations May Pose Different Risks for Heart Attack and Stroke https://www.cedars-sinai.edu/About-Us/News/News-Releases-2013/Study-Different-Hormone-Therapy-Formulations-May-Pose-Different-Risks-for-Heart-Attack-and-Stroke.aspx
135 Ovarian hormones affect the serotonin-producing neurons of the brain. Serotonin modifies gene expression. This impacts cognition, mood or arousal, hormone secretion, pain, and other neural circuits. Diverse Actions of Ovarian Steroids in the Serotonin Neural System ☆ Cynthia L. Betheaa, b, c, 1, Nick Z. Lua, c, Chrisana Gundlaha, 2, John M. Streichera, c, March 2002 http://www.sciencedirect.com/science/article/pii/S0091302201902250
136 Ovarian steroid hormones have effects on the brain throughout a woman's entire life, including areas that are not primarily involved in reproduction. This study focuses on those related to memory, and the effects of aging and oophorectomy. Ovarian steroids and the brain Implications for cognition and aging Bruce S. McEwen, PhD, Stephen E. Alves, PhD, Karen Bulloch, PhD and Nancy G. Weiland, PhD , May 1997 http://www.neurology.org/content/48/5_Suppl_7/8S.short

and

http://www.nbb.cornell.edu/neurobio/BioNB493/READINGS/lecture%2022/McEwenreview.pdf
137 Study focusing on the effects of estrogen on the dopaminergic system (neural pathways) in relation to movement disorders including Parkinsons. Estrogen and Movement Disorders. Kompoliti, Katie, Dec. 1999 http://journals.lww.com/clinicalneuropharm/Abstract/1999/11000/Estrogen_and_Movement_Disorders.3.aspx
138 Regulation of gonadotropins (FSH and LH) by activin and inhibin Semin Reprod Med. 2004 Aug;22(3):253-67. Regulation of gonadotropins by inhibin and activin. Gregory SJ1, Kaiser UB. http://www.ncbi.nlm.nih.gov/pubmed/15319828
139 Dopamine, serotonin, and norepinephrine (noradrenaline) and Parkinson's Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease Bernard Scatton1, France Javoy-Agid2, Liliane Rouquier1, Bruno Dubois2, Yves Agid2, September 1983 http://www.sciencedirect.com/science/article/pii/0006899383909939
140 The three endocrine axes, the HPA, HPG, and HPT, are complex and interconnected. Hormones produced by one influence those by others. The Endocrine System An Overview Susanne Hiller-Sturmh ö fel, Ph.D., and Andrzej Bartke, Ph.D, Alcohol Health and Research World, 1998 http://pubs.niaaa.nih.gov/publications/arh22-3/153.pdf
141 Excellent explanation of origination and conversion of steroid hormones in men and women. US Biotek Comprehensive Urinary Steroid Hormone Profile, Reference Guide https://www.usbiotek.com/Downloads/information/24_Hour_Interpretation_Guide.pdf
142 Understanding the mechanisms underlying hypothalamic–pituitary–gonadal axis-associated cognitive dysfunction is crucial for therapeutic advancement. Front Endocrinol (Lausanne). 2015 Mar 25;6:45. doi: 10.3389/fendo.2015.00045. eCollection 2015. Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer's disease: more than "just" estrogen. Blair JA1, McGee H1, Bhatta S1, Palm R2, Casadesus G1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373369/
143 Steroid hormone conversion Michael W King, PhD | © 1996–2014 themedicalbiochemistrypage.org, LLC http://themedicalbiochemistrypage.org/steroid-hormones.php
144 Large, decade-long study shows that women who take replacement estrogen had a 2.4x increase in incidence of lung cancer. International Journal of Cancer, Reproductive factors, hormone use and the risk of lung cancer among middle-aged never-smoking Japanese women: A large-scale population-based cohort study Ying Liu1, Manami Inoue1,†,*, Tomotaka Sobue2 andShoichiro Tsugane1 Article first published online: 31 MAY 2005 http://onlinelibrary.wiley.com/doi/10.1002/ijc.21229/full
145 2010 US Census 2010 US Census http://www.census.gov/2010census/data/
146 Women's reproductive cancer stats cancer.gov http://seer.cancer.gov/statfacts/html/corp.html
147 Cortisol, inflammation, stress, and cancer Dr. Brian Lawenda, Integrative Oncology Essentials http://www.integrativeoncology-essentials.com/2012/04/anticancer-lifestyle-stress-reduction-101/
148 Inhibin A + B as indicators of time until menopause Acta Obstet Gynecol Scand. 2005 Mar;84(3):281-5. Inhibin A and B as markers of menopause: a five-year prospective longitudinal study of hormonal changes during the menopausal transition. Overlie I1, Mørkrid L, Andersson AM, Skakkebaek NE, Moen MH, Holte A. http://www.ncbi.nlm.nih.gov/pubmed/15715537
149 Testosterone in men proven to be beneficial to arteries, insulin/blood sugar, fibrinolytic effects, and coronary artery circulation. Even with just a hysterectomy, and despite estrogen therapy, heart disease is 3x higher women than with women who don't have hyster. Studies about the effects of the loss of testosterone are critically needed. J Womens Health. 1998 Sep;7(7):825-9. Testosterone deficiency: a key factor in the increased cardiovascular risk to women following hysterectomy or with natural aging? Rako S. http://www.ncbi.nlm.nih.gov/pubmed/9785308
150 Menopausal ovaries make 40% of the body's testosterone and 20% of its androstenedione The climacteric ovary as a functional gonadotropin-driven androgen-producing gland. (PMID:8005293) Adashi EY University of Maryland School of Medicine, Baltimore. Fertility and Sterility [1994, 62(1):20-27] http://europepmc.org/abstract/med/8005293
151 Androgens and estrogen are both important to bone health Minerva Endocrinol. 2012 Dec;37(4):305-14. Androgens and bone. De Oliveira DH1, Fighera TM, Bianchet LC, Kulak CA, Kulak J. http://www.ncbi.nlm.nih.gov/pubmed/23235187
152 Melatonin, insomnia, oophorectomy, and estrogen Sleep Disorders in Women: From Menarche Through Pregnancy to Menopause: A Guide for Practical Management / Edition 1 by Hrayr P. Attarian (Editor) http://www.alibris.com/Sleep-Disorders-in-Women-A-Guide-to-Practical-Management/book/9539535
153 Role of dopamine and epinephrine deficiencies in women with disrupted HPA systems Neurotransmitters: Their Role in the Body WWW.RN.ORG ® Reviewed May 2013 , Expires May 2015 Provider Information and Specifics available on our Website Unauthorized Distribution Prohibited ©2013 RN.ORG®, S.A., RN.ORG®, LLC Developed by Melissa K. Slate, RN, BA, MA http://www.rn.org/courses/coursematerial-150.pdf
154 Estradiol and estrone reference ranges May Clinic Test ID: ESTF Estrogens, Estrone (E1) and Estradiol (E2), Fractionated, Serum http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84230
155 Review of known effects on Alzheimers, Parksinsons, depression of dysregulation of the HPA axis and impact on dopaminergic production Front Psychiatry. 2015; 6: 32. Published online 2015 Mar 9. doi: 10.3389/fpsyt.2015.00032 PMCID: PMC4353372 Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases? Xin Du1 and Terence Y. Pang2,* http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353372/
156 Stress, low cortisol, and high cytokines (cancer) J Trauma Stress. 2008 Dec; 21(6): 530–539. doi: 10.1002/jts.20372 PMCID: PMC2829297 NIHMSID: NIHMS116817 Low Cortisol, High DHEA, and High Levels of Stimulated TNFα, and IL-6 in Women with PTSD Jessica Gill, RN, PhD,corresponding author Meena Vythilingam, MD, and Gayle G. Page, RN, DNSc, FAAN http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829297/
157 Simple hysterectomy leads to 3x increase in likelihood heart disease Am J Obstet Gynecol. 1981 Jan;139(1):58-61. Premenopausal hysterectomy and cardiovascular disease. Centerwall BS. http://www.ncbi.nlm.nih.gov/pubmed/7457522
158 Androgens (testosterone) and urinary tract, incontinence Curr Opin Obstet Gynecol. 2004 Oct;16(5):405-9. Anabolic effects of androgens on muscles of female pelvic floor and lower urinary tract. Ho MH1, Bhatia NN, Bhasin S. http://www.ncbi.nlm.nih.gov/pubmed/15353950
159 It's all in your head - sex Relationship satisfaction predicts sexual activity following risk-reducing salpingo-oophorectomy. Lorenz T, et al. J Psychosom Obstet Gynaecol. 2014. http://www.ncbi.nlm.nih.gov/m/pubmed/24693956/?i=4&from=ovarian%20cancer%20and%20mental%20health
160 Testicular cancer stats American Cancer Society http://www.cancer.org/cancer/testicularcancer/detailedguide/testicular-cancer-key-statistics
161 Pancreatic cancer stats Cancer.org http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancreatic-cancer-key-statistics
162 Exogenous endocrine influencers and harm NIH: Endocrine Disruptors http://www.niehs.nih.gov/health/topics/agents/endocrine/
163 Rats gained weight for 3-5 weeks til 25% incr over pre-surgical weight The Effect of Estrogen on Appetite Disclosures Medscape General Medicine. 1998;1(3) http://www.medscape.com/viewarticle/722328_2
164 In WHI estrogen-alone study (Premarin), women taking oral estrogen had a risk of dementia that was 49% higher than the risk in women using the placebo. Half of those cases were Alzheimer's. NIH News - Estrogen-Alone Hormone Therapy Could Increase Risk of Dementia in Older Women http://www.nih.gov/news/pr/jun2004/nia-22.htm
165 Adrenals - inflammation and cancer Yale J Biol Med. 2006 Dec; 79(3-4): 123–130. Published online 2007 Oct. PMCID: PMC1994795 Cancer Issue Why Cancer and Inflammation? Seth Rakoff-Nahoum http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994795/
166 Obesity and androgen production Fertil Steril. 2006 May;85(5):1319-40. Obesity and androgens: facts and perspectives. Pasquali R1. http://www.ncbi.nlm.nih.gov/pubmed/16647374
167 PCOS definition and treatment womenshealth.gov Polycystic ovary syndrome (PCOS) fact sheet http://www.womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html#h
168 Excess insulin production tied to increased androgens and PCOS A Direct Effect of Hyperinsulinemia on Serum Sex Hormone-Binding Globulin Levels in Obese Women with the Polycystic Ovary Syndrome JOHN E. NESTLER, LINDA P. POWERS, DENNIS W. MATT, KENNETH A. STEINGOLD, STEPHEN R. PLYMATE, ROGER S. RITTMASTER, JOHN N. CLORE, and WILLIAM G. BLACKARD Address all correspondence and requests for reprints to: John E. Nestler, M.D., Division of Endocrinology and Metabolism, Medical College of Virginia, MCV Station, Box 111, Richmond, Virginia 23298–0111. *This work was supported in part by NIH Grants RR-00065 and DK-18904, a Research Award from the Virginia Affiliate of the American Diabetes Association, and the Thomas F. and Kate Miller Jeffress Memorial Trust. DOI: http://dx.doi.org/10.1210/jcem-72-1-83 Received: June 13, 1990 Published Online: July 01, 2013 http://press.endocrine.org/doi/abs/10.1210/jcem-72-1-83
169 Progesterone treatment for obese women with hyperplasia Discov Med. Author manuscript; available in PMC 2014 Mar 25. Published in final edited form as: Discov Med. 2012 Sep; 14(76): 215–222. PMCID: PMC3964851 NIHMSID: NIHMS564919 Catch It Before It Kills: Progesterone, Obesity, and the Prevention of Endometrial Cancer Matthew J. Carlson, M.D., Kristina w. Thiel, Ph.D., Shujie Yang, Ph.D., and Kimberly K. Leslie, M.D. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964851/
170 ZocDoc example of someone asking about pain after hysterectomy and being told the first place to look is psychology/it's "loss of womanhood" and pain is just psychosomatic ZocDoc What causes painful intercourse after hysterectomies? https://www.zocdoc.com/answers/4434/what-causes-painful-intercourse-after-hysterectomies
171 Levels below 40 IU/L FSH and an estradiol level below 50 pmol/L = ovarian failure - levels PubMed TI EMAS position statement: Managing women with premature ovarian failure. AU Vujovic S, Brincat M, Erel T, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K, Tremollieres F, Rozenberg S, Rees M, European Menopause and Andropause Society SO Maturitas. 2010;67(1):91. http://www.uptodate.com/contents/elective-oophorectomy-or-ovarian-conservation-at-the-time-of-hysterectomy/abstract/69
172 Hormone testing - saliva and serum - saliva only ok for cortisol. Others, serum is preferred. More accurate. Tissue vs free HuffPost Dr Julie Chen - Salivary Testing for Hormone Levels: Good Idea or Not? http://www.huffingtonpost.com/julie-chen-md/saliva-tests_b_4366310.html
173 Women who aren't BRCA 1 & 2 mutation risk ok, but those before menopause who are average risk should conserve, esp those with cardiovascular or neurological disease in family history Prophylactic and risk-reducing bilateral salpingo-oophorectomy: recommendations based on risk of ovarian cancer. AU Berek JS, Chalas E, Edelson M, Moore DH, Burke WM, Cliby WA, Berchuck A, Society of Gynecologic Oncologists Clinical Practice Committee SO Obstet Gynecol. 2010;116(3):733. http://www.ncbi.nlm.nih.gov/pubmed/20733460
174 Changes in optic pressure when steep Trendelenburg position is used during surgery can lead to blindness due to pressure on the optic nerve AANA Jounral, April 2011- Implications for Postoperative Visual Loss: Steep Trendelenburg Position and Effects on Intraocular Pressure, Bonnie Lee Molloy, CRNA, PhD, APRN http://www.aana.com/newsandjournal/documents/implications_0411_p115-121.pdf
175 Morcellator manufacturer in Germany threatens family with lawsuit for raising awareness about laparo/morcellation risk in hysterectomy surgery. Woman's believed fibroid turned out to be sarcoma and cancer was upstaged throughout her body. Morcellators were used in about 60,000 surgeries annually. Drugwatch - Device Maker Threatens Husband Who Launched Anti-Morcellation Campaign Posted September 2nd, 2014 by Michelle Llamas & filed under Defective Medical Devices. http://www.drugwatch.com/2014/09/02/karl-storz-threatens-morcellation-campaign/
176 Minimally-invasive surgery does not save hospitals money Charles Bankhead Staff Writer, MedPage Today http://www.medpagetoday.com/MeetingCoverage/SGO/31925
177 Hysterectomy is cost effective compared to ablation, etc. Vaginal is cheapest. Medscape: Overview of Current Trends in Hysterectomy Santiago Domingo; Antonio Pellicer Expert Rev of Obstet Gynecol. 2009;4(6):673-685. http://www.medscape.com/viewarticle/712569_3
178 ACOG hyperplasia guidelines ACOG Hyperplasia guidelines / FAQ http://www.acog.org/-/media/For-Patients/faq147.pdf?dmc=1&ts=20150527T1357417781
179 Endocrine Society PCOS recommendations Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline Richard S. Legro, Silva A. Arslanian, David A. Ehrmann, Kathleen M. Hoeger, M. Hassan Murad, Renato Pasquali, and Corrine K. Welt http://press.endocrine.org/doi/full/10.1210/jc.2013-2350
180 ACOG PCOS guidelines ACOG PCOS guidelines and FAQ http://www.acog.org/-/media/For-Patients/faq121.pdf?dmc=1&ts=20150527T1402397005
181 HysterSisters CEO Kathy Kelley speaks out against FDA warning on morcellators Empowher.com op-ed share: HysterSisters Responds to FDA Communication Limiting Hysterectomy Choices http://www.empowher.com/community/share/hystersisters-responds-fda-communication-limiting-hysterectomy-choices
182 Kathy Kelley speaks at robotic surgery conference where she is invited as "faculty" The 2nd World Robotic Gynecology Congress Agenda-WRGC II IGORS III World Robotic Gynecology Congress AND International Gynecologic Oncology Robotic symposium Partnering with the Fifth Annual World Robotic Symposium Disney’s Yacht and Beach Club, Walt Disney World®, Florida www.globalroboticsinstitute.com/wrs Scientific Sessions Interactive Surgical Tutorials Featuring 3D Technology • Multiple Live Telesurgery Transmissions • Tips and Tricks Hands-on Training On Site Full Robotic Surgery Certification (add on) • CME and CEU Credits • Allied Health (4/14/10) and Executive Tracks (4/11/10)  
183 Intuitive Surgical, makers of daVinci robot, listed as HysterSisters sponsor HysterSisters daVinci ad on website http://www.hystersisters.com/vb2/view_davinci_hysterectomy.htm
184 5,000+ articles on the benefits of daVinci hysterectomy Hystersisters.com "stories articles" http://www.hystersisters.com/vb2/articlelist_250.htm
185 daVinci laparoscopic robot indications for use in the US. Intuitive Surgical, maker of daVinci robot's, website. Indications for use page. http://www.intuitivesurgical.com/company/indications-for-use.html
186 Pfizer 2012 earnings Pfizer's site http://press.pfizer.com/press-release/pfizer-reports-fourth-quarter-and-full-year-2012-results-provides-2013-financial-guida
187 FDA Premarin WHI results FDA Safety Alerts section http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm153355.htm
188 FDA warning about PremPro after WHI
FDA Safety Alerts section http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm153358.htm
189 Natural vs synthetic hormones Herplace.com http://www.herplace.com/hormone-info/natural-vs-synthetic.htm
190 Premarin increases risk of dementia and mild cognitive impairment The Journal of the AMA, Original Contribution | June 23/30, 2004 Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal WomenWomen's Health Initiative Memory Study FREE Sally A. Shumaker, PhD; Claudine Legault, PhD; Lewis Kuller, MD, DrPH; Stephen R. Rapp, PhD; Leon Thal, MD; Dorothy S. Lane, MD, MPH; Howard Fillit, MD; Marcia L. Stefanick, PhD; Susan L. Hendrix, DO; Cora E. Lewis, MD; Kamal Masaki, MD; Laura H. Coker, PhD; for the Women's Health Initiative Memory Study http://jama.jamanetwork.com/article.aspx?articleid=198994
191 The WHI PremPro study demonstrated an increased risk of breast cancer of 25% over time of study, and a doubled risk of death from breast cancer over time of study (hazard ratio) in users of PremPro vs placebo. The Journal of the AMA, Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women FREE Rowan T. Chlebowski, MD, PhD; Garnet L. Anderson, PhD; Margery Gass, MD; Dorothy S. Lane, MD; Aaron K. Aragaki, MS; Lewis H. Kuller, MD; JoAnn E. Manson, MD, DrPH; Marcia L. Stefanick, PhD; Judith Ockene, MD; Gloria E. Sarto, MD; Karen C. Johnson, MD, MPH; Jean Wactawski-Wende, PhD; Peter M. Ravdin, MD, PhD; Robert Schenken, MD; Susan L. Hendrix, DO; Aleksandar Rajkovic, MD, PhD; Thomas E. Rohan, PhD; Shagufta Yasmeen, MD; Ross L. Prentice, PhD; for the WHI Investigators [+] Author Affiliations http://jama.jamanetwork.com/article.aspx?articleid=186747
191b Switching from oral to skin (transdermal) estradiol supplement, women's triglycerides went from 226 to 110 mg/dL. No changes in LDL or HDL cholesterol. Menopause. 2004 May-Jun;11(3):331-6. Substitution of transdermal estradiol during oral estrogen-progestin therapy in postmenopausal women: effects on hypertriglyceridemia. Sanada M1, Tsuda M, Kodama I, Sakashita T, Nakagawa H, Ohama K. http://www.ncbi.nlm.nih.gov/pubmed/15167313
192 Serum concentrations of triglyceride and very-low-density lipoprotein triglyceride decreased significantly after changing to transdermal estradiol (triglyceride, from 226.0 +/- 43.9 to 110.5 +/- 44.1 mg/dL, P < 0.01). No changes were seen in concentrations of low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. Menopause. 2004 May-Jun;11(3):331-6. Substitution of transdermal estradiol during oral estrogen-progestin therapy in postmenopausal women: effects on hypertriglyceridemia. Sanada M1, Tsuda M, Kodama I, Sakashita T, Nakagawa H, Ohama K. http://www.ncbi.nlm.nih.gov/pubmed/15167313
193 Estrogen is not enough. Testosterone is probably required for a full recovery. J Womens Health Gend Based Med. 2000 Oct;9(8):917-23. Testosterone supplemental therapy after hysterectomy with or without concomitant oophorectomy: estrogen alone is not enough. Rako S1. http://www.ncbi.nlm.nih.gov/pubmed/11074958
194 Oophorectomy reduces testosterone markedly. Oral estrogen decreases T bioavailability. T therapy needs to become part of replacement therapy. Womens Health (Lond Engl). 2012 Jul;8(4):437-46. doi: 10.2217/whe.12.27. Androgens in women before and after the menopause and post bilateral oophorectomy: clinical effects and indications for testosterone therapy. Davey DA1. http://www.ncbi.nlm.nih.gov/pubmed/22757734
195 Kathy Kelley CEO HysterSisters bio Hystersisters site http://www.hystersisters.com/vb2/press/BIO_Kathy_Kelley.pdf
196 Kathy Kelley's site manned by 30 volunteer "hostesses". Published booklet is in doctors' offices. She also teaches women about the goodness of God. Dallas Business Journal - June 2012 article, Kathy Kelley, HysterSisters http://www.bizjournals.com/dallas/print-edition/2012/06/08/kathy-kelley-hystersisters.html
197 Healthline article about whether daVinci robots are worth it to hospitals and the fact that many doctors think their straight to consumers marketing is criminal. "A solution in search of a problem" Is da Vinci Robotic Surgery a Revolution or a Ripoff? Written by Cameron Scott | Published on February 12, 2015 http://www.healthline.com/health-news/is-da-vinci-robotic-surgery-revolution-or-ripoff-021215#10
198 Former NYT writer opinion piece about HysterSisters exploitation of women asking about hysterectomies The Equalizer - Frances Cerra Whittelsey's blog http://theequalizerfcw.blogspot.com/2010/10/websites-exploit-women-worried-about.html
199 April 2014 FDA comm about morcellation Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication FDA issued an updated safety communication on November 24, 2014 Date Issued: April 17, 2014 http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm393576.htm
200 ACOG defines "informed consent". 'medical requests that are harmful can be refused' 'therapies with no benefit are unethical' 'accurate information' 'imbalance of power - honest information' ACOG site - Informed Consent http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Ethics/Informed-Consent
201 ACOG Code of Professional Ethics ACOG Code of Professional Ethics http://www.acog.org/-/media/Departments/National-Officer-Nominations-Process/ACOGcode.pdf
202 Women should be screened thoroughly before morcellation and data should be collected to determine whether women's health is at risk Obstet Gynecol. 2014 Oct; 124(4): 787–793. doi: 10.1097/AOG.0000000000000448 PMCID: PMC4377220 NIHMSID: NIHMS672178 Intracorporeal Electromechanical Tissue Morcellation A Critical Review and Recommendations for Clinical Practice Kimberly A. Kho, MD, MPH, Ted L. Anderson, MD, PhD, and Ceana H. Nezhat, MD http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377220/
203 Informed consent law by state in the US as of 2006 American Journal of Law & Medicine , 32 (2006): 429-501 © 2006 American Society of Law, Medicine & Ethics Boston University School of Law Rethinking Informed Consent: The Case for Shared Medical Decision- Making † Jaime Staples King †† and Benjamin Moulton http://allhealth.org/briefingmaterials/King-rethinkinginformedconsent-1943.pdf
204 Pfizer 2014 full year revenue reported - Premarin still #10 - 1 - PFIZER REPOR TS FOUR TH-QUAR TER AND FULL-YEAR 2014 RESUL TS; PROVIDES 2015 FINANCIAL GUIDANCE http://www.pfizer.com/system/files/presentation/Q4_2014_PFE_Earnings_Press_Release_alksdjindfls.pdf
205 World surgery statistics incl hysterectomy October 3, 2011 International variations in rates of selected surgical procedures across OECD countries Klim McPherson and Giorgia Gon http://www.oecd.org/els/health-systems/48831231.pdf
206 US has highest rate of hysterectomy in the world. Doctors are concurrently removing ovaries at the time of hysterectomy purportedly to address ovarian cancer risk which is small, and outweighed by the serious risks introduced by removal. Ovaries should be conserved past age 45 indefinitely. Overview of Current Trends in Hysterectomy Santiago Domingo; Antonio Pellicer Disclosures Expert Rev of Obstet Gynecol. 2009;4(6):673-685. http://www.medscape.com/viewarticle/712569_2
207

Modulation of activin in tissue repair

Recent studies have demonstrated a strong expression of activin in repair processes of various tissues and organs, including the skin, the lung, the intestine, the cardiovascular system, and even the brain. Although little is as yet known about the function of activin in tissue repair, first results suggest a role of activin in epithelial differentiation, fibroblast proliferation and expression of matrix molecules by these cells, and also in neuroprotection. Whereas a transient overexpression of activin after tissue injury might be beneficial for the repair process, sustained expression of activin could lead to fibrotic processes. Therefore, the modulation of the availability or biological activity of activin could be of particular importance for the treatment of impaired tissue repair on the one hand and tissue fibrosis on the other hand.

Histol Histopathol. 1999 Jan;14(1):295-304. Activin: a novel player in tissue repair processes. Hübner G1, Alzheimer C, Werner S. http://www.ncbi.nlm.nih.gov/pubmed/9987674/
208 Costs and outcomes of types of hysterectomies alone, hospital costs etc not addressed JSLS. 2012 Oct-Dec; 16(4): 519–524. doi: 10.4293/108680812X13462882736736 PMCID: PMC3558885 Costs and Outcomes of Abdominal, Vaginal, Laparoscopic and Robotic Hysterectomies Kelly N. Wright, MD,corresponding author Gudrun M. Jonsdottir, Selena Jorgensen, Neel Shah, MD, MPP, and Jon I. Einarsson, MD, MPH http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558885/
209 Women not being offered alternatives to hysterectomy for benign conditions, and doctors are using hysterectomy as a first line of defense in about 75% of cases. Main Street - Most Common Surgery in the U.S. For Women is Over-Prescribed Laura Kiesel Follow Jan 29, 2015 7:45 AM EST https://www.mainstreet.com/article/most-common-surgery-in-the-us-for-women-is-over-prescribed
210 an MRI using Gd-DTPA contrast combined with an LDH blood test is alleged accurate in diagnosing sarcoma prior to fibroid removal Int J Gynecol Cancer. 2002 Jul-Aug;12(4):354-61. Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus. Goto A1, Takeuchi S, Sugimura K, Maruo T. http://www.ncbi.nlm.nih.gov/pubmed/12144683
211 Diabetes risk increased by bilateral oophorectomy 60% more likely over 9 years of study Diabetes Journals - Bilateral Oophorectomy and the Risk of Incident Diabetes in Postmenopausal Women Duke Appiah1⇑, Stephen J. Winters2 and Carlton A. Hornung1 http://care.diabetesjournals.org/content/37/3/725.abstract
212 Activin and immune response, stem cell differentiation, glucose metabolism, actions in pituitary, follicle development, gonadal sex determination, and regulation. Good and thorough review of the role of activin within the system and the origin of its discovery (inhibin as well). J Endocrinol. Author manuscript; available in PMC 2010 Jul 1. Published in final edited form as: J Endocrinol. 2009 Jul; 202(1): 1–12. Published online 2009 Mar 9. doi: 10.1677/JOE-08-0549 PMCID: PMC2704481 NIHMSID: NIHMS114767 The Biology Of Activin: Recent Advances In Structure, Regulation And Function Yin Xia1 and Alan L. Schneyer2 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704481/
213 As inhibin is an indicator of ovarian cancer, activin is an indicator in post-menopausal women of breast tumors J Clin Endocrinol Metab. 2002 May;87(5):2277-82. Serum and tissue expression of activin a in postmenopausal women with breast cancer. Reis FM1, Cobellis L, Tameirão LC, Anania G, Luisi S, Silva IS, Gioffrè W, Di Blasio AM, Petraglia F. http://www.ncbi.nlm.nih.gov/pubmed/11994376
214 Johnson & Johnson known morcellator risk question being investigated by the FBI Healthfinder.gov - Cancer-Spreading Hysterectomy Device Focus of FBI Investigation http://www.healthfinder.gov/News/Article.aspx?id=699841&source=govdelivery&utm_medium=email&utm_source=govdelivery
215 Dr Rocca is interviewed by the Mayo Clinic about ovary removal risks Mayo Clinic Office Visit Prophylactic Oophorectomy An Interview With Walter Rocca, M.D. http://www.mayoclinic.org/documents/healthsource-pdf/doc-20079413
216 Decreases in ovarian cancer mortality attributed to better chemo drugs compared to the 1970s What's New in Ovarian Cancer TreatmentPublished on Sep 24, 2012 Sibley Memorial Hospital's Knowledge is Power lecture series on Ovarian Health. Presented by Mildred R. Chernofsky, M.D., on September 13, 2012. http://www.slideshare.net/SibleyMemorialHospital/epithelial-ovarian-cancer-presentation-by-mildred-chernofsky-md
217 American Cancer Society Facts and Figures 2014 - lung cancer info American Cancer Society Facts and Figures 2014 http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf
218 Women studied in 1971 after having ovaries removed between 1910 - 1940 at ages 15-30. Suicide rate was 2.7x (national average 0.0126%). Also young CVD, cardiac, high cholesterol, high cortisol, bone fractures. On some Late Effects of Bilateral Oophorectomy in the Age Range 15–30 Years B. W. Johansson, L. Kaij, S. Kullander*, H.-C. Lennér, L. Svanberg andB. Åstedt Article first published online: 12 JAN 2011 DOI: 10.3109/00016347509157108 http://onlinelibrary.wiley.com/doi/10.3109/00016347509157108/abstract
219 Women need to fight for better early ovarian cancer detection tools. Annual CA-125 measurement missed no invasive ovarian tumors, but because of the small size of study, annual screening not mandated. Ovarian cancer: why don't we ever talk about it? by Susan Gubar http://www.theguardian.com/society/2012/sep/01/ovarian-cancer-call-to-arms
220 Ovarian cancer screening accurately detected 86% of women with ovarian cancer, and ruled out almost 100% of women who were cancer-free. NHS UK: New test could improve diagnosis of ovarian cancer http://www.nhs.uk/news/2015/05May/Pages/New-ovarian-cancer-screening-technique-twice-as-effective.aspx
221 SEER ovarian cancer stats - repr 1.3% of all cancer cases. (Also 1.3% of women risk. 1% of non BRCA and 10-15% of ov cancer are BRCA.) SEER ovarian cancer stats http://seer.cancer.gov/statfacts/html/ovary.html
222 Dr. Lu 4,000 post-menopausal women screened frequently for raised CA-125 finds the regular screening was 99.9% dependable in finding ovarian cancer. CA-125 Monitoring Shows Benefit in Early Detection of Ovarian Cancer Ben Leach Published Online: Monday, August 26, 2013 http://www.onclive.com/web-exclusives/CA-125-Monitoring-Shows-Benefit-in-Early-Detection-of-Ovarian-Cancer
223 July 2013, The ACOG recently joined the ABIM's Choosing Wisely Campaign. #5 on the campaign's list is "don't screen for ovarian cancer in women at average risk" because they acknoweldge that women at average risk will not increase their risk by keeping their ovaries. (Note: This program used to be called the "Top 5" and is focused, truly, on containing costs) UK Hysterectomy Association website, latest news http://www.hysterectomy-association.org.uk/latest-news/acog-joins-the-choosing-wisely-campaign/
224 Dissertation addressing:
  • when incidental bilateral oophorectomy in women without risk factors was first introduced.
  • the scientific basis for the procedure’s use in women without risk factors.
  • why and how its use in women without risk factors became widespread.
  • when adverse health consequences associated with this procedure first appeared in the literature.
  • the severity of adverse health consequences reported in the literature over time.
  • the response of specialists to these scientific publications.
  • the role of acog practice guidelines in the use of this procedure in women without risk factors.
Current Oncology.com Vol 18, No 1, 2011, Evidence-based medicine: an analysis of prophylactic bilateral oophorectomy at time of hysterectomy for benign conditions, C.A. Larson , PhD * * University of Kentucky, Lexington, KY http://www.current-oncology.com/index.php/oncology/article/view/744/597
225 All sex hormones affect cardio, bone, cognitive, sexual response, and sexual attractiveness. Peri-menopausal changes occur in both adrenal and ovarian hormone production. One in two women is offered a hysterectomy, a rate 5 times higher than in European countries where comparable data is available. 90% of US hysters are for benign conditions. Side effects include sexual dysfunction, CV and bone disease, more rapid aging. No data suggests that hysterectomy is more effective than alternatives that don't have these side effects. The cascade of difficulties after surgery must be addressed, brought on by loss of estrogen, progesterone, and androgens. Dis Mon. 1998 Sep;44(9):421-546. Wellness in women after 40 years of age: the role of sex hormones and pheromones. Cutler WB1, Genovese-Stone E. http://www.ncbi.nlm.nih.gov/pubmed/9803240
226 This study showed that women who underwent bilateral oophorectomy before age 45 years were at increased risk of neurological or mental diseases. This risk was not modified by estrogen treatment from the time of oophorectomy through age 45 years. Our preliminary findings suggest a possible association of bilateral oophorectomy with ALS or MS that deserves further investigation. Increased Mortality for Neurological and Mental Diseases following Early Bilateral Oophorectomy Cathleen M. Rivera,a Brandon R. Grossardt,b Deborah J. Rhodes,a and Walter A. Roccac,d, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697609/
225 Who is measuring the benefit, if any, of prophylactic oophorectomy, given its known impact on the endocrine system, and link to CVD and osteoporosis. Calif Med. 1958 Jul;89(1):30-2. The controversial ovary. CULINER A. http://www.ncbi.nlm.nih.gov/pubmed/13561114
226 Testosterone is needed for prostate cancer to proliferate. Testosterone production comes the testes. However, testes are rarely removed today. It's irreversible, and has significant psychological impact. Rev Urol. 2009 Spring; 11(2): 52–60. PMCID: PMC2725306
Effective Testosterone Suppression for Prostate Cancer: Is There a Best Castration Therapy? Leonard G Gomella, MD
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725306/
227 Where is the evidence that removing ovaries prevents cancer? Then a TON of data about the relative risk, increased survival rate, and all the harm done by ovary removal. Women were 8.5% less likely to live to age 80 if they remove their ovaries at hysterectomy at ages 50-54 than if they keep them. Grand Rounds: Hysterectomy sans oophorectomy: The case for leaving a woman's ovaries alone. If there's no cancer present, why remove a woman's ovaries during hysterectomy? Does the reduced risk of ovarian cancer outweigh the consequences of eliminating the protective hormones secreted by a healthy pair of ovaries? A team of researchers offers some thought-provoking conclusions.

Jul 1, 2006 By: William H. Parker, MD , Michael S. Broder, MD, MPH , Jonathan S. Berek, MD, MMSc Contemporary OB/GYN
http://www.pharllc.com/wp-content/uploads/2013/03/Parker-Contemp-Obstet-Gynecol-2006.pdf
228 The history of ovary removal for various reasons in the last 200 years. As British gynaecologist Louise McIlroy10 (1874–1968) stated in 1912, the ovary is not an organ with the single role of reproduction, but is an essential factor in the maintenance of the equilibrium which exists between the so‐called ductless glands or endo‐secretory organs. Researches into ovarian function now tend to show that the removal of ovaries for slight pathological affections, or for the alleviation of menstrual derangements, is against the best ultimate interests of the patient, and that total extirpation of the ovaries should not be practised unless these organs are the seat of some severe pathological lesion. J Epidemiol Community Health. 2007 Mar; 61(3): 182–184. doi: 10.1136/jech.2006.046474 PMCID: PMC2652903 Prophylactic oophorectomy: a historical perspective Ornella Moscucci and Aileen Clarke http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652903/
229 Vasopressin levels lower in women at hysterectomy whose ovaries were removed than those whose were retained. Though vasopressin regulates fluid balance, no fluid balance changes were seen edspite lower serum levels. Estradiol enhanced and testosterone suppressed vasopressin release. Women not receiving estradiol saw no change in oxytocin levels, but women who did receive estradiol saw a significant drop in oxytocin at 8 and 12 months. Findings consistent with animal trials. The effect of oophorectomy and hormone replacement on neurohypophyseal hormone secretion in women Authors Forsling ML1, Anderson CH, Wheeler MJ, Raju KS., First published: January 1996Full publication history DOI: 10.1046/j.1365-2265.1996.633455.xView/save citation http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.1996.633455.x/full
230 The role of oxytocin in people 10 Reasons Why Oxytocin Is The Most Amazing Molecule In The World 579,524 9 George Dvorsky Filed to: Daily 10 7/12/12 10:20am http://io9.com/5925206/10-reasons-why-oxytocin-is-the-most-amazing-molecule-in-the-world
231 Steroid hormones affect vasopressin and oxytocin expression. Exp Physiol. 2000 Mar;85 Spec No:171S-177S. The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo-neurohypophysial explants from the rat. Sladek CD1, Swenson KL, Kapoor R, Sidorowicz HE. http://www.ncbi.nlm.nih.gov/pubmed/10795920
232 Testosterone probably affects oxytocin receptor binding after it aromatases to estrogen bc estrogen affects receptor binding. Neuroendocrinology 1989;50:199–203 (DOI:10.1159/000125222) Testosterone Modulates Oxytocin Binding in the Hypothalamus of Castrated Male Rats Johnson A.E.a · Coirini H.b · McEwen B.S.b · Insel T.R.a http://www.karger.com/Article/Abstract/125222
233 Lower androgen levels in women tied to decreased muscle mass, bone density, sex drive, and sense of well-being. J Med Invest. 2012;59(1-2):12-27. Androgen in postmenopausal women. Yasui T1, Matsui S, Tani A, Kunimi K, Yamamoto S, Irahara M. http://www.ncbi.nlm.nih.gov/pubmed/22449989
234 Poor-quality Jacoby study (http://www.ncbi.nlm.nih.gov/pubmed/21518944) using WHI data attempts to disprove Parker et al study data, and instead only proves that women in study didn't have the need for prophylactic surgery. Downplayed is the only statistically-relevant finding - that women with BSO before age 40 had a HR of 1.0 to the 0.72 of women who had not. Why poor quality: 1) Incl 13,000 women with BSO but only followed for 7.6 years, rather than the 30 years of Parker study; 2) Claim HRT played no role in outcome, which is unlikely and points to likely inaccuracy; 3) Unclear the number of women who'd had hysterectomy in their 40's or younger, which represents 52% of benign cause hysterectomies in US, and mean age was 63; 4) Participants BSO was self-reported, not verified; 5) survivor bias; 6) confounding potential of unmeasured variables. Doctors commenting said that this meant that the decision should be left up to doctors and patients... Some Benefit Seen for Ovary Removal at Hysterectomy by John Gever Senior Editor, MedPage Today http://www.medpagetoday.com/OBGYN/GeneralOBGYN/26118
235 Of the 1M women in China who have a hysterectomy every year, it's estimated that 35% have an oophorectomy at the same time. Front Med. 2014 Dec;8(4):464-70. doi: 10.1007/s11684-014-0338-y. Epub 2014 Jun 27. Comparison of surgical indications for hysterectomy by age and approach in 4653 Chinese women. Jiang J1, Ding T, Luo A, Lu Y, Ma D, Wang S. http://www.ncbi.nlm.nih.gov/pubmed/24972646
236 CNN reports that ACOG says that, despite advice from ACOP that pelvic exams are not necessary, women should still have them. They say that they will still find ovarian cysts and fibroids. (Important here to note that fibroids are the leading cause of hysterectomies for benign conditions, and that ACOG only wants to screen for cervical cancer now with a pap 1 in 3 years, and that the ACOG added screening for ovarian cancer to the Choosing Wisely list of things they won't be doing, so why a pelvic exam still matters annually should be explained.) Think twice before you skip the stirrups: Why I will still get a pelvic exam By Elizabeth Cohen, Senior Medical Correspondent, July 9, 2014 http://www.cnn.com/2014/07/09/health/pelvic-exam-opinion/
237 Oophorectomy led to significantly higher TC, LDL, Apo-B and arteriosclerosis index in patients. Influence of bilateral oophorectomy upon lipid metabolism Yoshio Suda , Hiroaki Ohtacorrespondence , Kazuya Makita , Kiyoshi Takamatsu , Fumi Horiguchi , Shiro Nozawa Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan Received: July 14, 1997; Received in revised form: November 22, 1997; Accepted: November 24, 1997; http://www.maturitas.org/article/S0378-5122%2897%2900089-3/abstract
238 In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being. September 7, 2000 The New England Journal of Medicine TRANSDERMAL TESTOSTERONE TREATMENT IN WOMEN WITH IMPAIRED SEXUAL FUNCTION AFTER OOPHORECTOMY J AN L. S HIFREN , M.D., G LENN D. B RAUNSTEIN , M.D., J AMES A. S IMON , M.D., P ETER R. C ASSON , M.D., J OHN E. B USTER , M.D., G EOFFREY P. R EDMOND , M.D., R EGULA E. B URKI , M.D., E LIZABETH S. G INSBURG , M.D., R AYMOND C. R OSEN , P H .D., S ANDRA R. L EIBLUM , P H .D., K IM E. C ARAMELLI , M.S., AND N ORMAN A. M AZER , M.D., P H .D. http://www.regulabuerki.ch/files/pdf/en/Transdermal%20Testosterone%20Treatment%20in%20Women.pdf
239 Medical malpractice is the 3rd leading cause of death in the U.S., behind heart disease and cancer, only. 10 Things You Want To Know About Medical Malpractice Comment Now Follow Comments malpractice By Demetrius Cheeks http://www.forbes.com/sites/learnvest/2013/05/16/10-things-you-want-to-know-about-medical-malpractice/
240 Though the cancer was diagnosed at a 1.21 rate ratio compared to those who were not screened using CA-125 testing and tv u/s, false positives resulted in a rate of serious complications of 15% in the women who were treated for diagnosed ovarian cancer. The 15% risk of serious complication is not offset by the value of the screening as it's done today. Trial involved 78,216 women ages 55-74 from Nov 1993 to July 2001. (DM note: Of note is that the deaths in the screened group were 3/10 of 1% and in the non-screened 2.5/10 of 1% in the non-screened. Ovarian cancer rate is indeed very low.) June 8, 2011, Vol 305, No. 22 > < Previous Article Next Article > Original Contribution | June 8, 2011 Effect of Screening on Ovarian Cancer MortalityThe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial FREE Saundra S. Buys, MD; Edward Partridge, MD; Amanda Black, PhD, MPH; Christine C. Johnson, PhD, MPH; Lois Lamerato, PhD; Claudine Isaacs, MD; Douglas J. Reding, MD, MPH; Robert T. Greenlee, PhD, MPH; Lance A. Yokochi, MD, PhD; Bruce Kessel, MD; E. David Crawford, MD; Timothy R. Church, PhD, MS; Gerald L. Andriole, MD; Joel L. Weissfeld, MD, MPH; Mona N. Fouad, MD; David Chia, PhD; Barbara O’Brien, MPH; Lawrence R. Ragard, MD; Jonathan D. Clapp; Joshua M. Rathmell; Thomas L. Riley, BS; Patricia Hartge, ScD, MA; Paul F. Pinsky, PhD; Claire S. Zhu, PhD; Grant Izmirlian, PhD; Barnett S. Kramer, MD; Anthony B. Miller, MD; Jian-Lun Xu, PhD; Philip C. Prorok, PhD; John K. Gohagan, PhD; Christine D. Berg, MD; for the PLCO Project Team [+] Author Affiliations JAMA. 2011;305(22):2295-2303. doi:10.1001/jama.2011.766 http://jama.jamanetwork.com/article.aspx?articleid=900666
241 Births per woman in the US (and other countries) Fertility rate, total (births per woman) http://data.worldbank.org/indicator/SP.DYN.TFRT.IN
242 Inpatient surgery data shows 2010 hysterectomies in U.S. numbered 498,000 CDC Inpatient Surgery Faststats http://www.cdc.gov/nchs/fastats/inpatient-surgery.htm
243 From 1992 to 2012, surgeries in total were up 17%. Outpatient surgeries at all community hospitals were up 54%. Abdominal or vaginal hysterectomy was one of the top 25 ambulatory/outpatient surgeries and was done on outpatient basis 39.8% of the time, representing 1.7% of all outpatient surgeries. However, "other OR excision of cervix or uterus" is a separate stat, and represents another 2.2% of all outpatient surgeries. Whether this stat includes laparoscopic hysterectomy (the notes say it refers "predominantly (to) uterine ablation," which isn't helpful), is difficult to determine, but this stat as outpatient represents 85.9% of procedures as outpatient. AHRQ H-CUP Statistical Brief #188, Feb 2015, Surgeries in Hospital - Owned Outpatient Facilities , 2012 Lauren M. Wier, M.P.H., Claudia A. Steiner, M.D., M.P.H., and Pamela L. Owens, Ph.D. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb188-Surgeries-Hospital-Outpatient-Facilities-2012.pdf
244 "The laparoscopic-assisted vaginal hysterectomy and the more recently developed complete laparoscopic hysterectomy can be performed in an outpatient setting since they allow faster recovery times for women. In 2003, 9 percent of hysterectomies were performed on an outpatient basis The mean age for an outpatient hysterectomy was 41 years, or 5 years less than the mean age for an inpatient hysterectomy (data not shown). Over half of all hysterectomies were performed on women 18 to 44 years of age, followed by nearly 40 percent for women ages 45 to 64. However, this distribution varied depending on inpatient or outpatient setting: women ages 18 to 44 accounted for 67 percent of outpatient hysterectomies. Less than one-third of these procedures performed in an outpatient venue occurred in women 45 to 64 years of age." Data table above says outpatient hysters in 2003 in US Hospitals represented 8.6% of all hysters performed. Based on citation #24, if 3.1 m were performed in 5 years of 2000-2004, that's 620K/yr and then if another 8.6% is done outpatient, that's a total of 678,336, not 600K.
US Dept of HHS, AHRQ, Healthcare Cost & Utilization Project (HCUP) Ambulatory Surgery in U.S. Hospitals, 2003 http://archive.ahrq.gov/data/hcup/factbk9/factbk9c.htm
245 UnitedHealth insurer tightens hysterectomy approval process Wall Street Journal, Biggest U.S. Health Insurer Tightens Rules on Hysterectomy Coverage, By Jennifer Levitz and Jon Kamp Updated Feb. 26, 2015 8:55 p.m. ET http://www.wsj.com/articles/biggest-u-s-health-insurer-tightens-rules-on-hysterectomy-coverage-1424990877
246 Unnecessary surgeries explored via the case of one man's career-ending, unnecessary pacemaker. USA Today, Doctors perform thousands of unnecessary surgeries, Peter Eisler and Barbara Hansen, USA TODAY 1:34 a.m. EDT June 20, 2013 http://www.usatoday.com/story/news/nation/2013/06/18/unnecessary-surgery-usa-today-investigation/2435009/
247 Elizabeth Cohen, Sr CNN Medical Correspondent, encourages others in op-ed to have GYN exams deemed medically unnecessary by the ACOP, who don't stand to gain financially. Exams lead to unnecessary procedures. The pelvic exam has nothing to do with whether or not women have their previously annual, now once every three years cervical exam, aka pap smear. The idea that this exam is not medically necessary because of the basis on the Greek study should lead to another question - why AREN'T we, in the U.S., studying the medical value of this test and not relying on her sense that, "yikes," she would prefer it. Think twice before you skip the stirrups: Why I will still get a pelvic exam By Elizabeth Cohen, Senior Medical Correspondent Updated 4:29 PM ET, Wed July 9, 2014 http://www.cnn.com/2014/07/09/health/pelvic-exam-opinion/
248 Majority of men would use male contraceptive pill Hum Reprod. 2000 Mar;15(3):637-45. Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations. Martin CW1, Anderson RA, Cheng L, Ho PC, van der Spuy Z, Smith KB, Glasier AF, Everington D, Baird DT. http://www.ncbi.nlm.nih.gov/pubmed/10686211
249 UK scientist Baird says that women serve no real purpose after menopause in that they are in an "unbiological" state. HRT and Osteoporosis edited by James O. Drife, John W.W. Studd https://books.google.com/books?id=aIDlBwAAQBAJ&pg=PA21&lpg=PA21&dq=kanis+baird+unbiological&source=bl&ots=p1BygYu3xj&sig=DiZljBsOMSQTlE36jne4lt5x3kU&hl=en&sa=X&ei=xzqLVbr8K9bWoATkiIO4Aw&ved=0CB8Q6AEwAA#v=onepage&q=kanis%20baird%20unbiological&f=false
250 NHS advances in reduction of incidence of low-value procedures including hysterectomy for heavy bleeding in top 3. England’s NHS provides starter lessons on improving value English National Health Service’s Savings Plan May Have Helped Reduce The Use Of Three ‘Low-Value’ Procedures By Sophie Coronini-Cronberg, Honor Bixby, Anthony A. Laverty, Robert M. Wachter and Christopher Millett Health Affairs, March 2015 http://www.pnhp.org/news/2015/march/england%E2%80%99s-nhs-provides-starter-lessons-on-improving-value
251 Australian women's health site provides honest feedback about risks and benefits of hysterectomy and ovary removal Hysterectomy Fact Sheet - Queensland Women's Health http://www.womhealth.org.au/conditions-and-treatments/211-hysterectomy
252

Dr. Parker lists risks and benefits of ovary removal and a model for determining when and when not.

About 50% of women who have a hysterectomy between ages 40-44 ovaries are removed, and 78% of women between ages 45-64 undergoing a hysterectomy ovaries are removed.

During the 28 years of follow-up, 44 of the 13,305 women (0.9 percent) who kept their ovaries died from ovarian cancer. While breast cancer and ovarian cancer were less frequent in women who had their ovaries removed, the overall risk of death from all types of cancer was higher among women who had their ovaries removed.



Journal of Family Practice, Remove the ovaries at hysterectomy? Here’s the lowdown on risks and benefits Oophorectomy causes more harm than good in many women undergoing hysterectomy for benign disease February 2010 · Vol. 22, No. 02 William H. Parker, MD

and

Our Bodies Ourselves, Hysterectomy and Ovarian Conservation By William H. Parker, MD | April 21, 2009 Last Revised on May 29, 2014

http://www.obgmanagement.com/home/article/remove-the-ovaries-at-hysterectomy-heres-the-lowdown-on-risks-and-benefits/09d1e503f7725af35b55e428505898fb.html

and

http://www.ourbodiesourselves.org/health-info/hysterectomy-and-ovarian-conservation/

253 Dr. Hill provides a thorough look at abnormal uterine bleeding and how to treat it without rushing to hysterectomy Journal of Family Practice, Abnormal uterine bleeding: Avoid the rush to hysterectomy Patients with heavy bleeding may think hysterectomy is their only recourse, but research supports other alternatives. J Fam Pract. 2009 March;58(3):136-142. http://www.jfponline.com/index.php?id=22143&tx_ttnews[tt_news]=174222
254 Women share experiences with ablation, myomectomy, and hyster/ooph. CNN, Nancy Larson, updated 9:59 a.m. EST, Mon March 3, 2008, Experts: Two-thirds of hysterectomies unnecessary http://www.cnn.com/2008/HEALTH/03/03/healthmag.hysterectomy/index.html?iref=newssearch
255 Duke study of 900 women aged 30-47 over 5 years, half had hysterectomy, half didn't. Women who had hyster had rate of early menopause due to ovarian failure of 14.8% vs 8% of women who didn't have surgery. Risk highest when one ovary also removed. As part of interview, Dr. Moorman said "doctors have long known that early menopause ­-- either from surgery or from other factors that halt egg production -- can increase a woman's risk of osteoporosis, heart disease, and other ailments." Hysterectomy Increases Risk for Earlier Menopause In Younger Women By Duke Medicine News and Communications, Nov 2011 http://corporate.dukemedicine.org/news_and_publications/news_office/news/hysterectomy-increases-risk-for-earlier-menopause-among-younger-women
256 Dr Marie Savard on sparing ovaries at hysterectomy in 2009 Home > Health > Health Spare the Ovaries! What Women Should Ask Before a Hysterectomy May 24, 2009 COMMENTARY By MARIE SAVARD, M.D. ABC News Medical Contributor http://abcnews.go.com/Health/CancerPreventionAndTreatment/story?id=7658406
257 British Journal of Science article about complications of hysterectomies contains data about rate of ovary removal at 73% , not 55%. Says rate of removal in UK is 20%. (as of 2004) The study also compares the risks associated with various types of hysterectomies. States menopause onset when ovaries conserved is average 3.7 years earlier. Bri tish Journal of Science 78 October 2013 , Vol. 9 ( 2 ) © 201 3 British Journals ISSN 2047 - 3745 Complications of Hysterectomy : A Review DR IA YAKASAI http://www.ajournal.co.uk/pdfs/BSvolume9%282%29/BSVol.9%20%282%29%20Article%208.pdf
258 Analysis of the bioethics of chemical castration specifically whether it limits or enhances sex offenders' autonomy J Bioeth Inq. 2013; 10(3): 393–405. Published online 2013 Jun 29. doi: 10.1007/s11673-013-9465-4 PMCID: PMC3824348 Coercion, Incarceration, and Chemical Castration: An Argument From Autonomy Thomas Douglas,corresponding author Pieter Bonte, Farah Focquaert, Katrien Devolder, and Sigrid Sterckx http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824348/
259 Informed consent, malpractice, and battery in medicine are discussed. Trans Am Ophthalmol Soc. 2004 Dec; 102: 225–232. PMCID: PMC1280103 THE PARAMETERS OF INFORMED CONSENT Edward L Raab, MD JD*§ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280103/
260 Discussion about the association between removing fallopian tubes and preventing ovarian cancer. August 2012. cancer.org, Can Removing Fallopian Tubes Prevent Cancer ? August 28, 2012 By Debbie Saslow, PhD http://www.cancer.org/cancer/news/expertvoices/post/2012/08/28/can-removing-fallopian-tubes-prevent-cancer-.aspx
261 Society of Gynecologic Oncology says that including fallopian tube removal in strategy to approach to ovarian cancer warrants inclusion in approach to prevention. Cancer. 2015 Mar 27. doi: 10.1002/cncr.29321. [Epub ahead of print] Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Walker JL1, Powell CB, Chen LM, Carter J, Bae Jump VL, Parker LP, Borowsky ME, Gibb RK. http://www.ncbi.nlm.nih.gov/pubmed/25820366
262 Women with hysterectomy and bilateral oophorectomy have a HR of 1.57 compared to women with no hysterectomy or oophorectomy. Clinical Advisor, February 26, 2014 Hysterectomy, oophorectomy raise diabetes risk http://www.clinicaladvisor.com/web-exclusives/hysterectomy-oophorectomy-raise-diabetes-risk/article/335730/
263 18-year National Cancer Institute finds that ovarian cancer screening does more harm than good because it leads to unnecessary procedures, says Dr. Christine Berg, head of early detection, National Cancer Institute. Ovarian cancer screening does more harm than good, study shows An 18-year study by the National Cancer Institute finds that ultrasounds and blood tests aimed at early detection don't save lives, but expose women to avoidable complications. June 12, 2011|By Jill U. Adams, Special to the Los Angeles Times http://articles.latimes.com/2011/jun/12/health/la-he-ovarian-cancer-20110612
264 The vast majority of ovarian cancer deaths are caused by high-grade serous tumors strongly associated with lesions in the fallopian tubes of women at low risk for the malignancy. Only 10-15% of ovarian cancers occur in women with a BRCA mutation or other predisposing gene. With hysterectomy and tubal sterilizations, it potentially makes sense to remove fallopian tubes prohlactically. Salpingectomy is proven unlikely to make a difference in ovarian function. Doctors in British Columbia are leading the way with proph. salpingectomy, and say a study should be top priority. Oncology Practice.com, Paradigm shift: Prophylactic salpingectomy for ovarian cancer risk reduction By: BRUCE JANCIN, Oncology Practice Digital Network September 24, 2014 http://www.oncologypractice.com/index.php?id=4892&type=98&tx_ttnews[tt_news]=300465&cHash=da03e20e36
265 Vasopressin fell in women who had ovaries removed, though fluid balance, regulated by vasopressin, didn't change. Exogenous estradiol and testosterone enhanced and repressed vasopressin release, respectively. Plasma oxytocin wasn't affected by ovary removal, but women receiving exogenous estradiol had significantly lower levels of oxytocin at 8-12 months than at 6 days post-op. Vasopressin release is influenced by gonadal hormones. Vasopressin regulates water retention and smooth muscle contractions. It also influences sexual behavior, public communication, and paternal behavior. Low vasopressin is tied to a rare form of diabetes called diabetes insipidus. High vasopressin is tied to depression. It improves cognitive ability through enhanced memory. Oxytocin is involved in mother-child bonding, social interactions, and romance. Clin Endocrinol (Oxf). 1996 Jan;44(1):39-44. The effect of oophorectomy and hormone replacement on neurohypophyseal hormone secretion in women. Forsling ML1, Anderson CH, Wheeler MJ, Raju KS.

and

Oxytocin, Alcohol Seem to Work on Brain in Similar Ways Last Updated: 2015-May-20 :: (HealthDay) By -- Robert Preidt

and

Hormones, Sex and Personality Type by Dario Nardi, Bulletin of Psychological Type, Volume 26, No 4, 2003

http://www.ncbi.nlm.nih.gov/pubmed/8706291

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https://lahey.org/Departments_and_Locations/Departments/Gynecology/Ebsco_Content/Oophorectomy.aspx?chunkiid=921731


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http://www.darionardi.com/BulletinArt9.html
266 Study of the role of oxytocin in the body under various conditions. (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo–pituitary–adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca2+ in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. CNS Neurosci Ther. 2010 Oct; 16(5): e138–e156. doi: 10.1111/j.1755-5949.2010.00185.x PMCID: PMC2972642 Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy Cedric Viero,1 Izumi Shibuya,2 Naoki Kitamura,2 Alexei Verkhratsky,3,4 Hiroaki Fujihara,5 Akiko Katoh,5 Yoichi Ueta,5 Hans H Zingg,6 Alexandr Chvatal,3,7 Eva Sykova,7,8 and Govindan Dayanithi3 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2972642/
267 Effects of androgens and estrogens on vasopressin levels in intact and castrated male and female rats. Effects of Sex Steroid Hormones on Arginine Vasopressin in Intact and Castrated Male and Female Rats RONALD W. SKOWSKY, LUCINDA SWAN, and PHILIP SMITH Address requests for reprints to: Dr. Ronald Skowsky, V.A. Hospital, 5901 East Seventh Street, Long Beach, California 90822. DOI: http://dx.doi.org/10.1210/endo-104-1-105 Received: April 18, 1978 First Published Online: July 01, 2013 http://press.endocrine.org/doi/abs/10.1210/endo-104-1-105
268 Role of the nonapeptide oxytocin as the social hormone. Role in greed and empathy. Naughty or Nice? A Brain Chemical May Tell by Wynne Parry | December 17, 2012 09:49am ET http://www.livescience.com/25587-greed-empathy-oxytocin.html
269 About 75% of ovarian cancers and 90% of deaths result from epithelial ovarian cancer, which likely arises from the fallopian tubes. Salpingectomy May Prevent Ovarian Cancer, ACOG Says Veronica Hackethal, MD December 31, 2014 http://www.medscape.com/viewarticle/837414
270 Virginia malpractice and informed consent cases Virginia malpractice and informed consent cases http://www.brienrochelaw.com/tort-law/tort-case-law/c/consent/
271

Example of informed consent form for abdominal hsyterectomy with possible BSO: "If the ovaries are to be removed, this will result in surgically induced menopause, which could result in a variety of symptoms, including, but not limited to, hot flashes, night sweats, mood disturbances, sleep disorders, vaginal dryness that could cause pain with intercourse, decreased sexual libido, and/ or osteoporosis. Although the intent is to completely remove the ovaries, it is possible a small remnant of ovarian tissue could be left behind resulting in ov arian remnant syndrome – a situation where a cyst develops from the remnant, possibly causing pelvic pain."

Women's Health Center of Lebanon, Ltd. in Lebanon, PA Revised 12/7/09 INFORMED CONSENT TO ABDOMINAL HYSTERECTOMY WITH POSSIBLE BILATERAL SALPINGO OOPHORECTOMIES http://www.whclebanon.com/pdfs/Informed_Consent_TAH_with_BSO.pdf
272 Oophorectomy reduces ovarian cancer risk 80% not 100%. Journal of the American Medical Association, July 12, 2006 Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation, Amy Finch, MS; Mario Beiner, MD; Jan Lubinski, MD, PhD; Henry T. Lynch, MD; Pal Moller, MD; Barry Rosen, MD; Joan Murphy, MD; Parviz Ghadirian, PhD; Eitan Friedman, MD; William D. Foulkes, MD; Charmaine Kim-Sing, MD; Teresa Wagner, MD; Nadine Tung, MD; Fergus Couch, PhD; Dominique Stoppa-Lyonnet, MD; Peter Ainsworth, MD; Mary Daly, MD; Barbara Pasini, MD; Ruth Gershoni-Baruch, MD; Charis Eng, MD; Olufunmilayo I. Olopade, MD; Jane McLennan, MD; Beth Karlan, MD; Jeffrey Weitzel, MD; Ping Sun, PhD; Steven A. Narod, MD; for the Hereditary Ovarian Cancer Clinical Study Group http://jama.jamanetwork.com/article.aspx?articleid=211067
273 The meaning of informed consent and how it differs in one half of the country from the other. (prudent patient vs community standard). The elements of the claim are (1) the physician did not present the risks and benefits of the proposed treatment and of alternative treatments; (2) with full information, the patient would have declined the treatment; and (3) the treatment, even though appropriate and carried out skillfully, was a substantial factor causing the patient’s injuries. Trans Am Ophthalmol Soc. 2004 Dec; 102: 225–232. PMCID: PMC1280103 THE PARAMETERS OF INFORMED CONSENT Edward L Raab, MD JD*§ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280103/
274 Choosing Wisely, informed consent, "Thomas Martin md , chair of ob / gyn , with twenty-eight years of clinical practice, on the weight given to acog guidelines said, “The guidelines provide parameters, but allow for individual clinical judgment. You don’t want to handcuff the doctor.” Martin emphasized the need to get patients engaged in decision-making on this elective procedure and concluded the interview with the observation that “It’s their gonads. No man asks to have his testicles removed”"

"Schmitt recommended that an article summarizing the findings be submitted to “The Green Journal” ( Obstetrics and Gynecology ), acog ’s official publication, which would provide the broadest dissemination across the ob / gyn specialty. That article, submitted in 2009, was declined for publication with no opportunity for revision." "Dr. Ablin, a member of the editorial board of Oncology News , issued invitations to publish the dissertation research findings in Current Oncology and Oncology News. " "Given that the acog practice guidelines were found to play a significant role in the persistence of oophorectomy in women at low risk, a second objective with the research was to work toward revised acog practice guidelines, because those guidelines serve as the medical–legal floor for the specialists." Reformed consent and accountability are also important.

Current Oncology, Vol 21, No 1 (2014), Larson Guest Editorial Prophylactic bilateral oophorectomy at time of hysterectomy for women at low risk: acog revises practice guidelines for ovarian cancer screening in low-risk women a C.A. Larson , PhD * *University of Kentucky, Lexington, KY, U.S.A. doi: http://dx.doi.org/10.3747/co.21.1721 http://www.current-oncology.com/index.php/oncology/article/view/1721/1402#b26-conc-21-9
275 Lack of informed consent against a health care provider may be within scope of the Consumer Protection Act if it relates to the entrepreneurial aspect of the medical practice. Dr. Carol Rusk, Univ. of Puget Sound Law Review, VOL 11:347, 1988 http://digitalcommons.law.seattleu.edu/cgi/viewcontent.cgi?article=1851&context=sulr
276 The role of DHT in oophorectomized rats with respect to osteporosis. Because testosterone converts to estrogen, measuring the effect of DHT is a better measure of the role of androgens. It decreased bone resorption. Journal of Bone & Mineral Research, Effects of Dihydrotestosterone on Bone Biochemical Markers in Sham and Oophorectomized Rats R. A. Mason* andH. A. Morris Article first published online: 1 SEP 1997 http://onlinelibrary.wiley.com/doi/10.1359/jbmr.1997.12.9.1431/full
277 Jan 2015 ACOG committee opinion sent out to 57,000 members and published in Green Journal re new thinking about salpingectomy to prevent ovarian cancer. "Salpingectomy for Ovarian Cancer Prevention ABSTRACT: Ovarian cancer has the highest mortality rate out of all types of gynecologic cancer and is the fifth leading cause of cancer deaths among women. Current attempts at screening for ovarian cancer have been unsuccessful and are associated with false-positive test results that lead to unnecessary surgery and surgical complications. Prophylactic salpingectomy may offer clinicians the opportunity to prevent ovarian cancer in their patients. Randomized controlled trials are needed to support the validity of this approach to reduce the incidence of ovarian cancer. The approach to hysterectomy or sterilization should not be influenced by the theoretical benefit of salpingectomy. Surgeons should continue to observe and practice minimally invasive techniques." ACOG Committee Opinion, Number 620, January 2015 http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Salpingectomy-for-Ovarian-Cancer-Prevention
278 The results come from analysis of one arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), the world’s largest ovarian cancer screening trial, led by UCL and funded by the Medical Research Council, Cancer Research UK, Department of Health and The Eve Appeal. The trial involved 202,638 post-menopausal women aged 50 or over who were randomly assigned to two different annual screening strategies (multimodal screening or transvaginal ultrasound) or no test at all. The study, published in the Journal of Clinical Oncology, evaluated 46,237 women who continued to attend annual multimodal screening following the first screen. Their blood was tested once a year for CA125 levels and then a computer algorithm was used to interpret their risk of ovarian cancer based on factors including the woman’s age, the original levels of CA125 and how that level changed over time. The serial pattern was compared with known cases of cancer and controls to estimate the risk of having ovarian cancer. The new method detected cancer in 86% of women with invasive epithelial ovarian cancer (iEOC), whereas the conventional test used in previous trials or in clinical practice would have identified fewer than half of these women (41% or 48% respectively). “There is currently no national screening programme for ovarian cancer, as research to date has been unable to provide enough evidence that any one method would improve early detection of tumours. These results are therefore very encouraging. They show that use of an early detection strategy based on an individual’s CA125 profile significantly improved cancer detection compared to what we’ve seen in previous screening trials. UCL News, New screening technique could pick up twice as many ovarian cancer cases 5 May 2015 https://www.ucl.ac.uk/news/news-articles/0515/020415-ovarian-cancer-screening-detection
279 Men's reaction to not having an annual prostate screening opposite of women's (CNN health for women's) Forbes, Contributor Steven Salzberg, 11/11/2013 @ 8:00AM 59,248 views Great News For Guys: No More Invasive Prostate Exams! http://www.forbes.com/sites/stevensalzberg/2013/11/11/great-news-for-guys-no-more-invasive-prostate-exams/
280 Whether a woman starts early or late with estrogen therapy, study shows there is no "critical window" benefit wrt verbal memory, cognitive, or executive function. Medscape, No Cognitive Difference Between Early, Late Estrogen Therapy Miriam E. Tucker October 19, 2014 http://www.medscape.com/viewarticle/833463
281 ACOG PAC donations ACOG PAC donations - opensecrets https://www.opensecrets.org/pacs/pacgot.php?cycle=2014&cmte=C00364158
282 Dysregulation of HPG axis with meno and andropause supported as causal to onset of Alzheimer's Disease. Hormones of the HPG axis are important regulators of cell growth and development. Think typo - should say use of "exogenous" hormones at close to premenop serum levels delays and decreases onset of Alzheimer's. J Neuropathol Exp Neurol. 2005 Feb;64(2):93-103. Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. Atwood CS1, Meethal SV, Liu T, Wilson AC, Gallego M, Smith MA, Bowen RL. http://www.ncbi.nlm.nih.gov/pubmed/15751223
283 Estrogen plays a significant role in oxytocin production in the CNS. After 48 hrs estrogen treatment, levels of oxytocin were 4.4x higher than ovariectomized female rats in the ventromedial nucleus of the hypothalamus. They were 3.18, 1.76, and 2.55x higher in the amygdala, hippocampus, and anterior pituitary. No changes in levels in the putamen, or the arcuate nucleus. Neuroendocrinology 1997;65:9–17 (DOI:10.1159/000127160) Effects of Estrogen on Oxytocin Receptor Messenger Ribonucleic Acid Expression in the Uterus, Pituitary, and Forebrain of the Female Rat Quiñones-Jenab V.a · Jenab S.a · Ogawa S.a · Adan R.A.M.b · Burbach J.P.H.b · Pfaff D.W.a aLaboratory of Neurobiology and Behavior, The Rockefeller University, New York, N.Y., USA; bRudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, The Netherlands http://www.karger.com/Article/Abstract/127160
284 Studying the connection between the role of gonadal steroid production and its influence over HPA activity. Effect is mediated through involvement of central oxytocin neurotransmission. Endocrinology. 2006 May;147(5):2423-31. Epub 2006 Jan 26. Gonadal steroid modulation of stress-induced hypothalamo-pituitary-adrenal activity and anxiety behavior: role of central oxytocin. Windle RJ1, Gamble LE, Kershaw YM, Wood SA, Lightman SL, Ingram CD. http://www.ncbi.nlm.nih.gov/pubmed/16439458
285 Interactions between the gonadal steroid hormones and vasopressin and oxytocin. Ann N Y Acad Sci. 1993 Jul 22;689:438-54. Interactions between the gonadal steroid hormones and vasopressin and oxytocin. Share L1, Crofton JT. http://www.ncbi.nlm.nih.gov/pubmed/8373024
286 "This opioid-adrenergic interaction itself appears to be central in the regulation of gonadotrophin secretion and mediation of the feedback effects of gonadal steroids in the brain." J Endocrinol. 1985 Dec;107(3):437-46. Endogenous opioid peptides and hypothalamic neuroendocrine neurones. Bicknell RJ. http://www.ncbi.nlm.nih.gov/pubmed/2999285
287 Disruption of the HPG axis leads to earlier mortality Age (Dordr). 2013 Feb; 35(1): 129–138. Published online 2011 Dec 4. doi: 10.1007/s11357-011-9342-1 PMCID: PMC3543732 Hypothalamic–pituitary–gonadal axis homeostasis predicts longevity James A. Yonker, Vicky Chang, Nicholas S. Roetker, Taissa S. Hauser, Robert M. Hauser, and Craig S. Atwoodcorresponding author http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543732/
288 To estimate rate of obgyn procedures performed on women (this was really related to the fact that female US population is estimated acc to US census to grow by 50% by 2050 compared to 2010 time of article) to understand obgyn future staffing needs. Incidental to that, it's revealed that it's understood for reasons of their own in the OBGYN community that the govt needs to include outpatient/emergency/ambulatory data in its numbers to accurately estimate the number of procedures being performed, as an increasing number are outpatient. Data from NHDS (National Hospital Discharge Survey) 1965-1987 and 1988-2006 only came from 8% of US non-federal short-stay hospitals (only 270,000 discharges). In some cases, estimates were extrapolated from as few as 61 cases per year in the DB. The govt only looked at outpatient data from 1994 to 1996 and then again for only one year in 2006. This data was collected in the National Survey of Ambulatory Surgery (NSAS). Obstet Gynecol. 2010 Oct; 116(4): 926–931. doi: 10.1097/AOG.0b013e3181f38599 PMCID: PMC3253706 NIHMSID: NIHMS281259 Trends Over Time With Commonly Performed Obstetric and Gynecologic Inpatient Procedures Sallie S. Oliphant, MD,1 Keisha A. Jones, MD,1 Li Wang, MS,2 Clareann H. Bunker, PhD,2 and Jerry L. Lowder, MD, MSc1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253706/
289 Yale doc Philip Sarrel part of team in 2001 that studies 664 postmeno women mean age 71 who had ischemic stroke or attack recently. Using 1 mg of e2-17beta a day, after 2.8 year follow-up, study's goal was to see if estrogen reduced their risk of stroke and death. Instead, they found that stroke and death was 10% higher with estrogen. The found that death risk was 20% higher. They found that nonfatal stroke was same, but risk of fatal stroke was 2.9 times higher and their nonfatal strokes were associated with worse neurologic and functional deficits. N Engl J Med. 2001 Oct 25;345(17):1243-9. A clinical trial of estrogen-replacement therapy after ischemic stroke. Viscoli CM1, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. https://www.ncbi.nlm.nih.gov/pubmed/11680444
290 All the stuff Pfizer has been up to (doesn't include the equine estrogen animal rights issue, but pretty much everything else). Corporate Research Project, Pfizer By Philip Mattera http://www.corp-research.org/pfizer
291 Marketing prescription drugs to consumers NIH article, history of DTC ads Am J Public Health. 2010 May; 100(5): 793–803. doi: 10.2105/AJPH.2009.181255 PMCID: PMC2853635 HIDDEN in PLAIN SIGHT Marketing Prescription Drugs to Consumers in the Twentieth Century Jeremy A. Greene, MD, PhDcorresponding author and David Herzberg, PhD http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853635/
292 Who in Congress is the ACOG PAC donating to in 2016 OpenSecrets ACOG PAC donations https://www.opensecrets.org/pacs/pacgot.php?cmte=C00364158&cycle=2016
293

Dr Sarrel NYT 1988 admits that while 75% of women experience menopause symptoms, an estimated 20% of men experience andropause symptoms that are similar. "Q. Do men escape from going through menopause? A. Not really. Studies show that about 25 percent of all men by the age of 60 experience a drop in hormone production and develop similar symptoms to what women experience, like sleep and sexual and disturbances and hot flashes."

"Q. Since the female body was meant to go through menopause and cease hormone production, isn't it better to leave the body alone and let nature take its course? A. I would extend that question to say we should never tinker with the body. There's a whole philosophy that says you should never take medicine, never have surgery. The point is, if you take that attitude then whatever happens, happens. Stay away from doctors. But if you want to live past 51, then you have to ask yourself, ''What else do I need to do in order to cope with life?'' And this is a quality of life issue."

New York Times, NY/Region, CONNECTICUT Q&A: DR PHILIP SARREL CONNECTICUT Q&A: DR PHILIP SARREL; 'This Is a Quality of Life Issue' By SHARON L. BASS Published: November 13, 1988 http://www.nytimes.com/1988/11/13/nyregion/connecticut-q-a-dr-philip-sarrel-this-is-a-quality-of-life-issue.html
294 Since women stopped taking HRT (Premarin, PremPro, WHI studies, NIH) as often, breast cancer diagnoses, esp of the kind influenced by estrogen, have dropped precipitously. Reversing Trend, Big Drop Is Seen in Breast Cancer By GINA KOLATA Published: December 15, 2006 http://www.nytimes.com/2006/12/15/health/15breast.html?pagewanted=all
295 Decreases in breast cancer diagnoses consistent with socioeconomic profile of women who took HRT. Am J Public Health. 2010 April; 100(Suppl 1): S132–S139. doi: 10.2105/AJPH.2009.181628 PMCID: PMC2837433 NIHMSID: NIHMS171687 Decline in US Breast Cancer Rates After the Women's Health Initiative: Socioeconomic and Racial/Ethnic Differentials Nancy Krieger, PhD,corresponding author Jarvis T. Chen, ScD, and Pamela D. Waterman, MPH http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837433/
296 The breast cancer study - statistically significant decline of 18% in incident invasive breast cancer diagnoses in women 45 and older and of estrogen-receptor positive cancer after estrogen use dropped 75% after WHI released data in 2002. Journal of the National Cancer Institute,

Breast Cancer Incidence, 1980–2006: Combined Roles of Menopausal Hormone Therapy, Screening Mammography, and Estrogen Receptor Status Andrew G. Glass, James V. Lacey Jr, J. Daniel Carreon and Robert N. Hoover + Author Affiliations Affiliations of authors: Oncology Research, Center for Health Research, Kaiser Permanente Northwest, Portland, OR (AGG); Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (JVL, JDC, RNH) Correspondence to: Andrew G. Glass, MD, Oncology Research, Center for Health Research, Kaiser Permanente Northwest, 3800 N Interstate Ave, Portland, OR 97227 (e-mail: andrew.glass@kpchr.org). Received September 11, 2006. Revision received May 11, 2007. Accepted June 11, 2007.
http://jnci.oxfordjournals.org/content/99/15/1152.full
297 NIH press release about the decrease in breast cancer rates being related to the reduction int he use of HRT. EMBARGOED FOR RELEASE Wednesday, April 18, 2007 5:00 p.m. EDT E-mail this page Subscribe CONTACT: NCI Office of Media Relations 301-496-6641 Decrease in Breast Cancer Rates Related to Reduction in Use of Hormone Replacement Therapy http://www.nih.gov/news/pr/apr2007/nci-18a.htm
298 What's old is new again. Pfizer / Wyeth used a campaign for decades that made women who went through menopause believe menopause was an illness. In 2012, this blog post provided an update on litigation around illnesses caused by the medication. Tuesday's Horse, Premarin and Prempro: The consequences of deception – A litany of litigation Mar 10, 2012 Jane Allin 21 Comments Written by JANE ALLIN https://tuesdayshorse.wordpress.com/2012/03/10/premarin-the-consequences-of-deception-a-litany-of-litigation/
299 Dr Naoh Kauff, Dir of Ovarian Cancer Screening & Prevention at Sloan-Kettering in NY, since 2002, no one should be doing oophorectomy without evidence of BRCA mutation.

"Changed Standard of Care “Surgery to reduce breast and ovarian cancer risk should only be recommended for women with a documented BRCA1 or BRCA2 mutation,” Dr. Kauff stressed. Two studies2,3 published simultaneously in the The New England Journal of Medicine in 2002, looking at the impact of risk-reducing salpingo-oophorectomy, “very rapidly changed the standard of care for women with BRCA1 or BRCA2 mutations,” according to Dr. Kauff, who was the lead author of one of those studies. “Our study showed a reduction in the combined risk of breast and gynecologic cancer by 75% in women who had risk-reducing surgery,” he said. “Since then, multiple additional studies have shown that BRCA1 and BRCA2 mutation carriers get anywhere from a 70% to 96% reduction in ovarian cancer risk and anywhere from a 40% to 70% reduction in breast cancer risk if the procedure is performed premenopausally,” Dr. Kauff stated. “It is very unusual for a woman at Memorial who is otherwise healthy and has a BRCA1 or BRCA2 mutation not to ultimately undergo risk-reducing salpingo-oophorectomy, either after childbearing is complete or after menopause. The vast majority of patients do have risk-reducing salpingo-oophorectomy,” Dr. Kauff said. “The reason risk-reducing salpingo-oophorectomy is so commonly used is that there is no good screening alternative for ovarian cancer.”"
'Reasonable but Not Required' for Women With BRCA Mutations to Have Hysterectomy Concurrent With Salpingo-Oophorectomy By Charlotte Bath December 1, 2013, http://www.ascopost.com/issues/december-1,-2013/reasonable-but-not-required-for-women-with-brca-mutations-to-have-hysterectomy-concurrent-with-salpingo-oophorectomy.aspx
300

Study published July 2013 stated 91,610 women died because they avoided posthysterectomy hormone therapy. (DM: They should not be having hysterectomies. Obviously, ovaries were removed, too.) WHI investigator says analysis is oversimplification that relies on inconclusive secondary subgroup analysis from a 2011 WHI publication. JoAnn Manson said it was rather a "mathematical exercise" (not really a study) based on "findings that are inconclusive."

Medscape, Analysis alleges excess deaths among women avoiding HRT Jenni Laidman July 25, 2013 http://www.medscape.com/viewarticle/793312
301 Thromboembolism occurred at a rate half again as much in women receiving Premarin as ones receiving placebo over mean of 7 years. (HR 1.47) Original Investigation | April 10, 2006 Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus FREE J. David Curb, MD; Ross L. Prentice, PhD; Paul F. Bray, MD; Robert D. Langer, MD, MPH; Linda Van Horn, MD, PhD; Vanessa M. Barnabei, MD, PhD; Michael J. Bloch, MD; Michele G. Cyr, MD; Margery Gass, MD; Lisa Lepine, MD; Rebecca J. Rodabough, MS; Stephen Sidney, MD, MPH; Gabriel I. Uwaifo, MD; Frits R. Rosendaal, MD, PhD http://archinte.jamanetwork.com/article.aspx?articleid=410075
302 Estrogen by itself could increase the risk of dementia in older women NIH News, EMBARGOED FOR RELEASE Tuesday, June 22, 2004 4:00 p.m. ET E-mail this page Subscribe CONTACT: Karin Kolsky 301-496-1752 Estrogen-Alone Hormone Therapy Could Increase Risk of Dementia in Older Women http://www.nih.gov/news/pr/jun2004/nia-22.htm
303

Looking at a separate group of women than those followed in the 2002 trial — women ages 50 to 59 who had had hysterectomies — Dr. Philip Sarrel and colleagues calculated that rejecting estrogen-only hormone therapy resulted in the early deaths of nearly 50,000 women between 2002 and 2011.

Sarrel: “Distortion of details can prove to be nothing less than lethal,” they wrote. “The Women’s Health Initiative findings need to be presented so that the very important differences between the two treatment modalities are emphasized and the benefits for hysterectomized women aged 50 to 59 years are appreciated. This effort has clearly been inadequate to date.”

UPDATED July 18, 3:59 p.m.: Dr. Rowan Chlebowski, an investigator at the Los Angeles Biomedical Research Institute, sounded a note of caution. "This paper does not present any new clinical trial results," he wrote in an email. "Rather it is an analysis based on aggressive assumptions." Chlebowski said that while the analysis might "support new hypotheses ... they do not provide reliable evidence to inform clinical practice or to make reliable claims about mortality consequences."


Avoiding estrogen therapy proved deadly for nearly 50,000: study July 18, 2013|By Eryn Brown | http://articles.latimes.com/2013/jul/18/science/la-sci-sn-estrogen-alone-hormone-therapy-deaths-20130718
304 The big WHI list of estrogen-alone links. This is the list of the letters they sent to participants, and all the data about why they stopped early. WHI Estrogen-Alone Study links http://www.nhlbi.nih.gov/whi/estro_alone.htm
305 Women who've had hysterectomy twice as likely to lose ovarian function. Data were gathered from the National Health and Examination Survey III, an in-person, structured interview of 20,050 noninstitutionalized civilians. The researchers analyzed data on menopausal status, surgery, smoking, and FSH levels (from a single blood sample) in 1716 women aged 35 to 39. Among 153 women with hysterectomy alone, 24% had FSH levels above 20 IU/L compared with 12% of 1481 age-matched women with a uterus (odds ratio, 1.5). An association was found between unilateral oophorectomy and elevated FSH levels in women who had not undergone a hysterectomy (OR, 2.8). Current cigarette smoking was associated with increased FSH levels, consistent with the known risk of menopause occurring 1 to 2 years earlier in cigarette smokers. NEJM, March 1, 2000 Hysterectomy Compromises Ovarian Function SA Carson reviewing Cooper GS and Thorp JM. Obstet Gynecol 1999 Dec. http://www.jwatch.org/wh200003010000008/2000/03/01/hysterectomy-compromises-ovarian-function
306 Taiwanese proph ooph at time of hyster rate down from 22% in 2000 to 10% in 2010, particularly in women 45-49 which was down 80%, likely due to new information about the harm done by prophylactic oophorectomy. Menopause. 2015 Jul;22(7):765-72. doi: 10.1097/GME.0000000000000360. Trends in bilateral salpingo-oophorectomy among Taiwanese women undergoing benign hysterectomy: a population-based, pooled, cross-sectional study. Lai JC1, Huang N, Wang KL, Hu HY, Chen IT, Chou YJ. http://www.ncbi.nlm.nih.gov/pubmed/25387346
307 Assoc editor of NEJM comments on post about ooph harm of CVD and says ACOG says premenopausal women should keep their ovaries at hysterectomy. February 19, 2009 Oophorectomy and Cardiovascular Risk Ann J. Davis, MD reviewing Rivera CM et al. Menopause 2009 Jan/Feb. Parker WH and Manson JE. Menopause 2009 Jan/Feb. http://www.jwatch.org/wh200902190000001/2009/02/19/oophorectomy-and-cardiovascular-risk
308 ACOG's brochure Women's Health Stats & Facts which states that the ovaries cease to function at menopause ACOG's 2011 Women's Health Stats & Facts http://www.acog.org/-/media/NewsRoom/MediaKit.pdf
309 ACOG president Dr. Mark DeFrancesco introduces himself on ACOG president blog acogpresident We Are Women’s Partners in Health, Posted on May 7, 2015 by Mark DeFrancesco, For the Times They Are A-Changin’ http://acogpresident.org/?p=1275
310 First published by Dr Lundberg in JAMA, now unable to find there. Malpractice third leading cause of death in the US Doctors Are The Third Leading Cause of Death in the US, Killing 225,000 People Every Year, July 2000 http://articles.mercola.com/sites/articles/archive/2000/07/30/doctors-death-part-one.aspx
311 CDC data, Women ages 45-64 have used anti-depressants within 30 days at a rate almost twice that of the national average Data table for Figure 25. Use of prescription antidepressants in the past 30 days among adults aged 18 and over, by sex and age: United States, 1988–1994 through 2007–2010 http://www.cdc.gov/nchs/data/hus/2013/fig25.pdf
312 70% of American trust their doctors and take their doctors advice without getting a second opinion, 2010 Gallup poll data, December 2, 2010 Most Americans Take Doctor's Advice Without Second Opinion http://www.gallup.com/poll/145025/americans-doctor-advice-without-second-opinion.aspx
313 Plaintiff in MD whose gyn removed her tubes and ovaries without consent is only awarded $547,500 because the gyn argued that she had not suffered any damages as a result of the surgery. Meanwhile, plaintiff in DC whose doctor removed two areas in her breast that he felt required biopsy rather than one was awarded $1.6 million. OBG Management - Medical Verdicts - June 2003 http://www.obgmanagement.com/fileadmin/obg_archive/pdf/1506/1506OBGM_MedicalVerdicts7.pdf
314 video: OB/GYNs discuss prophylactic oophorectomy Bilateral prophylactic oophorectomy https://www.youtube.com/watch?v=7YtTFuZj9EA
315 Types of hysterectomy Hopkins Medicine describes the types of hysterectomy http://www.hopkinsmedicine.org/healthlibrary/test_procedures/gynecology/hysterectomy_procedure_92,P07777/
316 Steroid hormone conversion charts The Medical Biochemistry Page - steroid hormones http://themedicalbiochemistrypage.org/steroid-hormones.php#introsteroid
317 Sexual victimization of children and adults is a significant treatment and public policy problem in the United States. To address increasing concerns regarding sex offender recidivism, nine states have passed legislation since 1996 authorizing the use of either chemical or physical castration. In most statutes, a repeat offender’s eligibility for probation or parole is linked to acceptance of mandated hormonal therapy. Future legal challenges to this wave of legislation will probably include arguments that such laws violate constitutional rights guaranteed to the offender by the First, Eighth, and Fourteenth Amendments. Castration of Sex Offenders: Prisoners’ Rights Versus Public Safety Charles L. Scott, MD, and Trent Holmberg, MD http://www.jaapl.org/content/31/4/502.full.pdf
318 Part IV examines whether the new statute violates several constitutional rights of the sentenced sex offender, namely the right to refuse non-consensual medical treatment, the right to privacy, the prohibition against cruel and unusual punishment, the right to due process and equal protection, and the protection against double jeopardy. Parts V and VI establish that civil libertarians will accept a probation program that provides voluntary drug treatment for sex offenders if the goal of the program is to treat, and not to punish, the sex offender. FLORIDA'S 1997 CHEMICAL CASTRATION LAW: A RETURN TO THE DARK AGES LARRY HELM SPALDING[*] Copyright © 1998 Florida State University Law Review http://archive.law.fsu.edu/journals/lawreview/frames/252/spalfram.html
319 Critics, including the American Civil Liberties Union (ACLU), charge that chemical castration violates sex offenders' constitutional rights. The ACLU contends that chemical castration violates an offender's implied right to privacy under the Fourteenth Amendment, rights of due process and equal protection, and the Eighth Amendment's ban of cruel and unusual punishment. FindLaw: Chemical and Surgical Castration http://criminal.findlaw.com/criminal-charges/chemical-and-surgical-castration.html
320 Robin Karr writes about the history of the legal and ethical question of castration of sex offenders vs the prevailing attitude towards ovary removal The Ethics of Female Castration: Hysterectomy Plus Ovariectomy Monday, May 13th, 2013 / Robin Karr http://www.hormonesmatter.com/ethics-of-total-hysterectomy-female-castration/
321 Effect of estrogen levels on skin (some of which is probably more attributable to activin) and tied to collagen Am J Clin Dermatol. 2001;2(3):143-50. Estrogen and skin. An overview. Shah MG1, Maibach HI. http://www.ncbi.nlm.nih.gov/pubmed/11705091
322 Examining the ability for skin collagen levels to act as corrolary for bone - collagen and bone, wrinkles Med Hypotheses. 2005;65(3):426-32. Osteoporosis, a unitary hypothesis of collagen loss in skin and bone. Shuster S1. http://www.ncbi.nlm.nih.gov/pubmed/15951132
323 Gonadal steroid deficiency has the greatest effect on bone loss during aging. Estrogen plays the dominant role in age-related bone loss in both men and women, largely due to increased resorption. An increase in SHBG, FSH, and LH with age reduces the amount of free, circulating hormones. As a result, from ages 23 - 90, men lose about 64% of T and 47% of E. SHBG increased by 124%, LH by 285% and FSH by 505%. Radiol Clin North Am. Author manuscript; available in PMC 2011 May 1. Published in final edited form as: Radiol Clin North Am. 2010 May; 48(3): 483–495. doi: 10.1016/j.rcl.2010.02.014 PMCID: PMC2901252 NIHMSID: NIHMS182903 Physiology of Bone Loss Bart L. Clarke, MDa,b and Sundeep Khosla, MDc,d http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901252/
324 Protect the Physician-Patient Relationship Oppose state and federal interference in the patient-physician relationship. ACOG's legislative priorities http://www.acog.org/Advocacy/ACOG-Legislative-Priorities
325 Rep Ami Bera speaks to the ACOG about the malpractice bill ACOG Pennsylvania Section Newsletter, A Converstation with Rep Ami Bera MD A “Conversation” with Representative Ami Bera, MD http://www.acog.org/About-ACOG/ACOG-Sections/Pennsylvania-Section/Newsletters/Spring-2014/A-Converstation-with-Representative-Ami-Bera-MD
326 Prostate cancer case Mims site

http://www.sfmlawyers.com/lawyer-attorney-1503890.html

327 Sarrel Reuters Hot flashes Untreated hot flashes may be costly for society : study NEW YORK | By Kathryn Doyle

http://www.reuters.com/article/2014/09/08/us-women-health-menopause-productivity-idUSKBN0H320G20140908

http://www.healthylivingmagazine.us/Articles/2491/

328 NEJM Daine Judge Sarrel hot flashes, Judge criticizes Sarrel conclusions NEJM Journal Watch, March 10, 2015 The High Cost of Hot Flashes Diane E. Judge, APN/CNP reviewing Sarrel P et al. Menopause 2015 Mar. Pinkerton JV. Menopause 2015 Mar. http://www.jwatch.org/na37194/2015/03/10/high-cost-hot-flashes
329

Citing Sarrel and others, MGH article on hot flashes

“Another way to look at the impact of menopausal symptoms is by measuring their financial burden. Looking at health insurance claims from 60 self-insured Fortune 500 companies in the United States between 1999 and 2011 , researchers examined healthcare resource utilization, work productivity loss (disability + medically related absenteeism), and associated costs in women with and without menopausal symptoms. So if we do the math, that’s $2,116 per woman per year in additional direct and indirect costs. Approximately 2 million American women become perimenopausal each year over the next decade. If we estimate that about 20% of those women will have moderate to severe vasomotor symptoms, untreated VMS will cost about $800 million per year. This is a problem we cannot afford to ignore. In an accompanying editorial, Dr. JoAnn Pinkerton states, “It is imperative that women’s healthcare providers must recognize that hot flashes are more than just a nuisance. Although it is true that hot flashes themselves are not life-threatening, they are disruptive to women, their lives, their families, and the workplace… The burden of persistent VMS rests not only on the women themselves and on their careers but also on their employers and families and on healthcare and workplace costs. Women deserve to be asked about the frequency and severity of their hot flashes and night sweats, with healthcare providers understanding that disruptive VMS need to be addressed with therapy.””

Mass General Hospital, The Immense Burden of Menopausal Symptoms By MGH Center for Women's Mental Health on May 4, 2015 in Menopausal Symptoms http://womensmentalhealth.org/posts/the-immense-burden-of-menopausal-symptoms/
330

Sarrel Yale News, “Not treating these common symptoms causes many women to drop out of the labor force at a time when their careers are on the upswing,” said Dr. Philip Sarrel, emeritus professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences, and Psychiatry. “This also places demands on health care and drives up insurance costs.”

The team found that women who experienced hot flashes had 1.5 million more health care visits than women without hot flashes. Costs for the additional health care was $339,559,458. The cost of work lost was another $27,668,410 during the 12-month study period.

In the past, hot flashes were readily treated with either hormone therapy or alternative approaches. However, following the 2002 publication of the findings in the Women’s Health Initiative Study, there has been a sharp drop in the use of hormone therapy due to unfounded fears of cancer risks, according to Sarrel. “Women are not mentioning it to their healthcare providers, and providers aren’t bringing it up,” said Sarrel. “The symptoms can be easily treated in a variety of ways, such as with low-dose hormone patches, non-hormonal medications, and simple environmental adjustments such as cooling the workplace.”

Yale News: The high cost of hot flashes: Millions in lost wages preventable By Karen N. Peart, August 27, 2014

http://news.yale.edu/2014/08/27/high-cost-hot-flashes-millions-lost-wages-preventable

331

Women who experienced hot flashes made 1.5 million more health care visits compared to women who did not experience hot flashes. Additional health care costs reached $339,559,458, while the cost of lost work wages climbed to another $27,668,410 throughout the course of the 12-month period. Aside from the issue of embarrassment, findings from the Women’s Health Initiative Study back in 2002 caused a sharp decline in the number of women who use hormone therapy to treat hot flashes due to an unfounded fear of cancer risk. Sarrel, No mention of Noven.

Embarrassment Over Hot Flashes Could Be Costing Women Millions In Lost Wages And Hospital Visits Aug 28, 2014 11:50 AM By Justin Caba http://www.medicaldaily.com/embarrassment-over-hot-flashes-could-be-costing-women-millions-lost-wages-and-hospital-300262
332

“Since 2009, one million women between the ages of 45 and 54 have dropped out of the work force, according to a New York Times article published in June.”

"The cost of the extra health care visits for menopausal women with hot flashes totaled nearly $340 million for health insurance companies. Work loss and work compensation added an additional $27 million."

Did not allude to conflict. Sarrel

EmpowHer/Erin Kennedy/Michelle King Robson When Hot Flashes Aren't Treated, It Costs the Economy Millions of Dollars

http://www.empowher.com/hot-flashes/content/when-hot-flashes-arent-treated-it-costs-economy-millions-dollars

333 Sarrel: “So what did they find? After calculating the health care costs over a 12-month follow-up period, the authors determined that women who experienced hot flashes had 1.5 million more visits to health care providers than those without VMS – and the cost for that additional health care was nearly $340 million. They added another $27.7 million in lost work. A few more stats: Women with hot flashes but who were untreated sought 82% more outpatient visits for medical care for any health reason than those not diagnosed with the malady. The mean direct costs per patient per year for these women amounted to $1,346. “But it’s important to realize that we’re all paying for the costs associated with not treating this,” says Patrick Lefebvre, a study co-author who works at the Analysis Group, a clinical research organization.” Wall Street Journal/Ed Silverman Aug 27, 2014 Hot News Flash: Untreated Menopause Costs the Economy Millions? http://blogs.wsj.com/pharmalot/2014/08/27/hot-news-flash-untreated-menopause-costs-the-economy-millions/
334 Sarrel hot flashes Ellen Dolgen Menopause Left Untreated Costs American Economy Hundreds of Millions of Dollars

http://ellendolgen.com/menopause-blog/2014/09/01/menopause-left-untreated-costs-american-economy-hundreds-of-millions-of-dollars/

335 Sarrel hot flashes Hot Flashes Cost Millions in Lost Wages By Nick Tate | Thursday, 28 Aug 2014 03:04 PM http://www.newsmax.com/Health/Anti-Aging/hot-flashes-cost-healthcare/2014/08/28/id/591470/
336 Sarrel hot flashes, economic and social costs of this practice are far greater than anything Dr. Sarrel alluded to. Hot Flashes May Cost Nearly $14 Billion Annually, Dr. Seibel

http://www.doctorseibel.com/diabetes/hot-flashes-cost-14-billion-annually/

337 Host Dr. Mache Seibel interviews Phil Sarrel, MD, Professor Emeritus from Yale, who has a new study showing hot flashes could cost the country over $14 Billion dollars annually and pull millions of women out of the workforce. My Menopause Magazine, Dr. Mache Seibel, BlogTalkRadio

http://www.blogtalkradio.com/mymenopauseradio/2014/08/27/hot-flashes-keep-million-out-of-work-dr-mache-seibel-with-dr-phil-sarrel

338 OBJECTIVE: Most women with moderate to severe vasomotor symptoms (VMS) are untreated. This retrospective matched-cohort study aims to evaluate the healthcare resource utilization, work loss, and cost burden associated with untreated VMS. METHODS: Health insurance claims (1999-2011) were used to match (1:1) women with untreated VMS with control women using propensity score. Healthcare resource utilization, work productivity loss (disability + medically related absenteeism), and associated costs were compared between cohorts. RESULTS: During the 12-month follow-up, women with untreated VMS (n = 252,273; mean age, 56 y) had significantly higher healthcare resource utilization than women in the control cohort: 82% higher for all-cause outpatient visits (95% CI, 81-83; P < 0.001) and 121% higher (95% CI, 118-124; P < 0.001) for VMS-related outpatient visits. Mean direct costs per patient per year were significantly higher for VMS women (direct cost difference, US$1,346; 95% CI, 1,249-1,449; P < 0.001). VMS women had 57% (95% CI, 51-63; P < 0.001) more indirect work productivity loss days than controls, corresponding to an incremental indirect cost per patient per year associated with untreated VMS of US$770 (95% CI, 726-816; P < 0.001). CONCLUSIONS: This study shows that untreated VMS are associated with significantly higher frequency of outpatient visits and incremental direct and indirect costs. Menopause. 2015 Mar;22(3):260-6. doi: 10.1097/GME.0000000000000320. Incremental direct and indirect costs of untreated vasomotor symptoms. Sarrel P1, Portman D, Lefebvre P, Lafeuille MH, Grittner AM, Fortier J, Gravel J, Duh MS, Aupperle PM.

http://www.ncbi.nlm.nih.gov/pubmed/25714236

339 Yale federal funds - Sarrel Yale Daily News - Yale federal funds at risk By Alison Griswold Staff Reporter Wednesday, August 31, 2011 http://yaledailynews.com/blog/2011/08/31/yale-federal-funds-at-risk/
340 OBGYN has routinely removed 1,300 healthy appendixes ResearchGate - Sohaib Khan Aga Khan University, Pakistan Any role of prophylactic appendectomy in patients with incidental appendicolith on CT scans? Should we offer prophylactic appendectomy to patients? http://www.researchgate.net/post/Any_role_of_prophylactic_appendectomy_in_patients_with_incidental_appendicolith_on_CT_scans
341 Updated on July 26, 2015 to correct Pfizer's annual revenue from the Premarin family of hormone therapy medication which I incorrectly updated with just one quarter's information, rather than the entire year. Pfizer's annual earnings Q4 2012 over 2011 http://press.pfizer.com/press-release/pfizer-reports-fourth-quarter-and-full-year-2012-results-provides-2013-financial-guida
342 Angelina Jolie - Scientific American - her case is very rare - surgery is wrong for most and carries many risks of its own. Scientific American - Removal of Ovaries, Fallopian Tubes Wrong Anticancer Option for Most Angelina Jolie Pitt is part of only a small subset of the population at such high risk for cancer that doctors recommend preventative surgery By Rebecca Harrington | March 27, 2015 http://www.scientificamerican.com/article/removal-of-ovaries-fallopian-tubes-wrong-anticancer-option-for-most/
343 Live Longer Slide presentation - HPG dysregulation consequences Prof. Craig Atwood PhD, prof at U of Wisconsin, Gerontology and Geriatrics http://www.slideshare.net/catwood66/living-longer-presentation-2012
344 "For women with an average risk of ovarian cancer (defined as women who do not have a document germline mutation or who do not have a strong family history suspicious for a germline mutation) who are undergoing a hysterectomy for benign conditions, the decision to perform bilateral salpingo-oophorectomy (BSO) should be individualized after appropriate informed consent, including a careful analysis of personal risk factors. There is evidence from observational studies that surgical menopause may negatively impact cardiovascular health and all-cause mortality. Ovarian conservation before menopause is particularly important in patients with a personal or strong family history of cardiovascular disease or stroke." Choosing Wisely used again to permit women without risk to have prophylactic BSO. Initiative title is misleading. Actual initiative describes appropriateness after informed consent. American Urogynecologic Society View all recommendations from this society May 5, 2015 Avoid removing ovaries at hysterectomy in pre-menopausal women with normal cancer risk. http://www.choosingwisely.org/clinician-lists/augs-ovary-removal-at-hysterectomay-in-pre-menopausal-women/
345 Though lacking control for temporal aspect of study, given the large number of women who have hysterectomies, it's worth noting that the surgery is significantly associated with a higher rate of renal cancer JAMA - Original Investigation | December 13/27, 2010 Risk of Renal Cell Carcinoma After Hysterectomy FREE Daniel Altman, MD, PhD; Li Yin, PhD; Anna Johansson, MSc; Cecilia Lundholm, MSc; Henrik Grönberg, MD, PhD [+] Author Affiliations Arch Intern Med. 2010;170(22):2011-2016. doi:10.1001/archinternmed.2010.425 http://archinte.jamanetwork.com/article.aspx?articleid=776467
346 There were 118 cases of thyroid cancer diagnosed, 103 papillary and 15 follicular or medullar type. The incidence for thyroid cancer was significantly elevated (standardized incidence ratio [SIR] 1.38, 95% CI 1.15-1.64). The increase in the incidence of thyroid cancer was not dependent on the extent of operation but on the length of follow-up. Thyroid cancer incidence was increased 0.5 to 1.4 years after hysterectomy (SIR 2.00, 95% CI 1.31-2.93), but decreased thereafter (SIR 1.30, 95% CI 0.99-1.67). Hysterectomy with and without oophorectomy was associated with a similar increase in the incidence of thyroid cancer. Am J Obstet Gynecol. 2003 Jan;188(1):45-8. Increased risk of thyroid cancer among women with hysterectomies. Luoto R1, Grenman S, Salonen S, Pukkala E. http://www.ncbi.nlm.nih.gov/pubmed/12548194
347 The history of the hysterectomy Baillieres Clin Obstet Gynaecol. 1997 Mar;11(1):1-22. Hysterectomy: a historical perspective. Sutton C1. Author information http://www.ncbi.nlm.nih.gov/pubmed/9155933
348 Women's testosterone peaks at ovulation J Sex Med. 2008 Apr;5(4):854-63. doi: 10.1111/j.1743-6109.2008.00791.x. Menstrual cycle-related changes in circulating androgens in healthy women with self-reported normal sexual function. Salonia A1, Pontillo M, Nappi RE, Zanni G, Fabbri F, Scavini M, Daverio R, Gallina A, Rigatti P, Bosi E, Bonini PA, Montorsi F. http://www.ncbi.nlm.nih.gov/pubmed/18371044
349 Testosterone supplements - On the basis of our analysis of 20 randomized, placebo-controlled trials, we can conclude that the hormone has a positive effect on sexual response, having been reported to increase pleasure from masturbation (37), sexual desire (26-28),, the frequency of sexual activity (26,27,38,40),, sexual satisfaction (38,40-43,47),, and orgasm (28,38,45,46). One of the trials (52) began in 2008 and is still under way (with an expected trial duration of approximately 5 years). These findings are consistent with those of other studies showing increases in sexual desire, the frequency of sexual activity, and sexual satisfaction in women receiving androgen therapy (53-55). Testosterone was found to have beneficial effects on libido regardless of the route of administration (oral administration, transdermal administration, or implants). However, in studies comparing two different doses of transdermal testosterone (i.e., 150 µg and 300 µg) in terms of their efficacy, testosterone was reported to have a beneficial effect on sexual response only when a 300-µg dose was used (40,45,46,56). Clinics (Sao Paulo). 2014 Apr; 69(4): 294–303. doi: 10.6061/clinics/2014(04)11 PMCID: PMC3971358 Benefits and risks of testosterone treatment for hypoactive sexual desire disorder in women: a critical review of studies published in the decades preceding and succeeding the advent of phosphodiesterase type 5 inhibitors Sandra Léa Bonfim ReisI and Carmita H. N. AbdoII http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971358/
350 Residency training in obstetrics and gynecology is being challenged by increasingly stringent regulations and decreased operative experience. We sought to determine the perception of preparedness of incoming gynecologic oncology fellows for advanced surgical training in gynecologic oncology. An online survey was sent to gynecologic oncologists involved in fellowship training in the United States. They were asked to evaluate their most recent incoming clinical fellows in the domains of professionalism, level of independence/graduated responsibility, psychomotor ability, clinical evaluation and management, and academia and scholarship using a standard Likert-style scale. The response rate among attending physicians was 40% (n = 105/260) and 61% (n = 28/46) for program directors. Of those who participated, 49% reported that their incoming fellows could not independently perform a hysterectomy, 59% reported that they could not independently perform 30 min of a major procedure, 40% reported that they could not control bleeding, 40% reported that they could not recognize anatomy and tissue planes, and 58% reported that they could not dissect tissue planes. Fellows lacked an understanding of pathophysiology, treatment recommendations, and the ability to identify and treat critically ill patients. In the academic domain, respondents agreed that fellows were deficient in the areas of protocol design (54%), statistical analysis (54%), and manuscript writing (65%). These results suggest that general Ob/Gyn residency is ineffective in preparing fellows for advanced training in gynecologic oncology and should prompt a revision of the goals and objectives of resident education to correct these deficiencies. Gynecologic Oncology Reports Volume 12, April 2015, Pages 55–60 Cover image Open Access Survey Article Preparedness of Ob/Gyn residents for fellowship training in gynecologic oncology David W. Dooa, , , Matthew Powellb, Akiva Novetskyb, Jeanelle Sheedera, Saketh R. Guntupallic Under a Creative Commons license Show more doi:10.1016/j.gore.2015.03.004 http://www.sciencedirect.com/science/article/pii/S2352578915000211
351

The "societal" cost of doing hysters abdominally vs with morcellator. (DM note: why not compare to LAVH if you're really interested in recovery times?)

Abstract Study Objective To estimate the cost-effectiveness of eliminating morcellation in the surgical treatment of leiomyomas from a societal perspective. Design Cost-effectiveness analysis. Design Classification Not applicable. Setting A theoretical cohort of women undergoing hysterectomy for myoma disease large enough to require morcellation. Patients None. Interventions None. Measurements A decision analysis model was constructed using probabilities, costs, and utility data from published sources. A cost-effectiveness analysis analyzing both quality-adjusted life years (QALYs) and cases of disseminated cancer was performed to determine the incremental cost-effectiveness ratio (ICER) of eliminating morcellation as a tool in the surgical treatment of leiomyomas. Costs and utilities were discounted using standard methodology. The base case included health care system costs and costs incurred by the patient for surgery-related disability. One-way sensitivity analyses were performed to assess the effect of various assumptions. Main Results The cost to prevent 1 case of disseminated cancer was $10 540 832. A strategy of nonmorcellation hysterectomy via laparotomy costed more ($30 359.92 vs $20 853.15) and yielded more QALYs (21.284 vs 21.280) relative to morcellation hysterectomy. The ICER for nonmorcellation hysterectomy compared with morcellation hysterectomy was $2 184 172 per QALY. Health care costs (prolonged hospitalizations) and costs to patients of prolonged time away from work were the primary drivers of cost differential between the 2 strategies. Even when the incidence of occult sarcoma in leiomyoma surgery was ranged to twice that reported in the literature (.98%), the ICER for nonmorcellation hysterectomy was $644 393.30. Conclusions Eliminating morcellation hysterectomy as a treatment for myomas is not cost-effective under a wide variety of probability and cost assumptions. Performing laparotomy for all patients who might otherwise be candidates for morcellation hysterectomy is a costly policy from a societal perspective. (DM: surgeons as market researchers for device makers.)

Journal of Minimally Invasive Gynecology Volume 22, Issue 5, Pages A1-A16, 705-920 (July–August 2015)

Cost-Effectiveness Analysis of Morcellation Hysterectomy for MyomasOriginal Research Article Pages 820-826 Pietro Bortoletto, Brett D. Einerson, Emily S. Miller, Magdy P. Milad

DM Notes: Bortoletto is a Boston OBGYN resident; Einerson was also a resident when this was done: McGaw Medical Center of Northwestern University
Residency, Obstetrics and Gynecology, 2011–2015 ; Emily S. Miller, MD, MPH (2014) Dr. Miller completed her residency at Northwestern University, Feinberg School of Medicine in Chicago and started her Fellowship with Maternal-Fetal Medicine in July 2011. She has completed her Master's in Public Health and her special interests include reproductive epidemiology and peripartum mental health. She joined the MFM faculty in August of 2014 at Northwestern as a WRHR scholar.

http://www.ncbi.nlm.nih.gov/pubmed/25827327
352 "Intensive media and policy attention has been focused on the ongoing controversy surrounding uterine morcellation in gynecologic surgery. What has been missing from this impassioned discourse is an objective analysis of the ethical implications of uterine power morcellation in gynecologic surgery. This article discusses competing ethical duties of physicians, industry, the U.S. Food and Drug Administration, and the media to develop a more robust and nuanced understanding of informed consent for the use of morcellation in benign gynecologic surgery. Ultimately, as physicians, we must remain steadfast in our dedication to the use of evolving technologies to better patient health in a safe and ethical manner that is well-studied, informed, and implemented with appropriate training and precautions. © 2014 by The American College of Obstetricians and Gynecologists." (DM: surgeons as market researchers for device makers.) Obstetrics and Gynecology Volume 124, Issue 6, 11 December 2014, Pages 1199-1201 Bits and pieces: The ethics of uterine morcellation (Article) Arora, K.S. , Spillman, M., Milad, M. Department of Obstetrics and Gynecology, MetroHealth Medical Center, and Department of Bioethics, Case Western Reserve University, Cleveland, Ohio; and Departments of Obstetrics and Gynecology, Baylor University, Waco, Texas, and Northwestern Memorial Hospital, Chicago, Illinois http://www.scopus.com/record/display.url?eid=2-s2.0-84916884514&origin=inward&txGid=E8448E8F41E2FD65E704A414660A7E13.fM4vPBipdL1BpirDq5Cw%3a2
353 Fibroids are the reason for a hysterectomy 40% of the time. Number 444, November 2009 (Reaffirmed 2011) Committee on Gynecologic Practice This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Choosing the Route of Hysterectomy for Benign Disease http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Choosing-the-Route-of-Hysterectomy-for-Benign-Disease
354 What happens to the ovaries in terms of hormonal function and morphology at the end of menopause. Histol Histopathol (2008) 23: 219-226 Offprint requests to: Dr. M. Laszczynska, Laboratory of Embryology, Pomeranian Medical University, Zolnierska 48, 71-210 Szczecin, Poland. e-mail: laszcz@sci.pam.szczein.pl http://www.hh.um.esHistology and Histopathology Cellular and Molecular Biology
Review Human postmenopausal ovary – hormonally inactive fibrous connective tissue or more? M. Laszczy ́ nska 1 , A. Brodowska 2 , A. Starczewski 2 , M. Masiuk 3 and J. Brodowski 4 1 Laboratory of Embryology, 2 Department of Reproduction and Gynaecology, 3 Department of Pathology, and 4 Laboratory of Family Nursing, Pomeranian Medical University, Szczecin, Poland
http://www.hh.um.es/pdf/Vol_23/23_2/Laszczynska-23-219-226-2008.pdf
355 HPG axis hormones and the aging brain Cell Mol Life Sci. 2005 Feb;62(3):257-70. The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain. Vadakkadath Meethal S1, Atwood CS. http://www.ncbi.nlm.nih.gov/pubmed/15723162
356 ACGME surgical accreditation minimums only include: vaginal deliveries, c-sections, ultrasounds, 3 forms of hysterectomy, pelvic floor procedures, 3 scoping procedure types, abortions, transvaginal ultrasounds, and surgery for invasive cancers. No myomectomy, cystectomies, ablations, embolizations, prolapse repair, or organ-sparing removal of endometriosis - the surgeries that treat the illness that is fibroids, heavy bleeding, and endometriosis that make up the three most common reasons alongside prolapse for hysterectomies. (DM comment: The training leads to the over-treatment.) ©2012 Accreditation Council for Graduate Medical Education (ACGME) Minimum Thresholds Obstetrics and Gynecology https://www.acgme.org/acgmeweb/Portals/0/PFAssets/ProgramResources/220_Ob_Gyn%20Minimum_Numbers_Announcment.pdf
357 Dr. Keith Isaacson defends uterine sarcoma morcellation. “I don’t care what number you pick. Let’s say the risk of cancer is 1 in 10 instead of 1 in 8,000,” he said. “I still think the patient should be involved in the decision-making process after a discussion of the benefits vs. the risks.” May 3, 2015 ACOG Annual Meeting http://www.acogdailynews.com/mathers-lecture-to-focus-on-power-morcellation-concerns/
358 OBGYNs do not train in general surgery at all. General Surgery News, May 2008 Op-ed, Residents Caught in Catch-22 of Education and Compliance by Stephanie Allen Lilly, MD http://generalsurgerynews.com/ViewArticle.aspx?d=Opinions%2B%26amp%3B%2BLetters&d_id=77&i=May%2B2008&i_id=407&a_id=10795
359 OOPHORECTOMY VERSUS CYSTECTOMY The indications for ovarian surgery versus expectant management of an ovarian cyst depend upon the patient's age, findings on pelvic examination and ultrasound, and laboratory results. These issues are discussed in depth separately. (See "Approach to the patient with an adnexal mass" and "Differential diagnosis of the adnexal mass".) When surgery is indicated for benign ovarian disease, preservation of ovarian tissue via cystectomy or enucleation of a solid tumor from the ovary is generally preferable to complete oophorectomy. When the ovary cannot be salvaged or insufficient viable tissue remains after attempts at conservation, oophorectomy is performed. In postmenopausal patients, no effort is made to preserve the ovary. Indications for oophorectomy include: (blank) UpToDate - Oophorectomy and ovarian cystectomy Authors Fidel A Valea, MD William J Mann, Jr, MD Section Editor Howard T Sharp, MD Deputy Editor Sandy J Falk, MD, FACOG http://www.uptodate.com/contents/oophorectomy-and-ovarian-cystectomy
360

OBGYNs across the world - training and salaries compared.

UK - 7 years
US - 4 years
AU - 6 years
UK - $187,771
US - $226,369
AU - not listed

Obstetrics and gynaecology From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Obstetrics_and_gynaecology
361 Use of robotic hysterectomy for endometrial cancer - societal cost analysis. (DM: Surgeons as market researchers for device makers.) Obstetrics and Gynecology International Volume 2011 (2011), Article ID 570464, 9 pages http://dx.doi.org/10.1155/2011/570464 Research Article The Feasibility of Societal Cost Equivalence between Robotic Hysterectomy and Alternate Hysterectomy Methods for Endometrial Cancer Neel T. Shah,1,2 Kelly N. Wright,1,2 Gudrun M. Jonsdottir,1 Selena Jorgensen,2 Jon I. Einarsson,1,2 and Michael G. Muto2,3 1Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA 2Harvard Medical School, Boston, MA 02115, USA 3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA Received 30 June 2011; Revised 20 September 2011; Accepted 25 September 2011 http://www.hindawi.com/journals/ogi/2011/570464/
362 1,491 peri and post-menopausal women completed survey card. Tested severity of vasomotor symptoms and sexual dysfunction. 17% had mod to severe VSM symptoms, 18% had mod to severe sexual dysfunction. 11% used hormone medication. Most likely to use HRT were those whose ovaries had been removed. 3.27x more likely. Smoking or high BMI negatively correlated. Findings were extrapolated to 3.7M australian women ages 40-64. (DM: They found a 385,000 woman market for HRT, essentially. Surgeons as market researchers for drug manufacturers.) Menopause: Post Author Corrections: July 31, 2015 doi: 10.1097/GME.0000000000000495 Original Study: PDF Only Low use of effective and safe therapies for moderate to severe menopausal symptoms: a cross-sectional community study of Australian women. Worsley, Roisin MBBS, FRACP; Bell, Robin J. MBBS, PhD; Gartoulla, Pragya MSc Epidemiology; Davis, Susan R. MBBS, FRACP, PhD http://journals.lww.com/menopausejournal/pages/articleviewer.aspx?year=9000&issue=00000&article=98137&type=abstract
363 "Robert Battey (1828–1895) introduced bilateral oophorectomy for the treatment of non-ovarian conditions in 1872, coining the term “normal ovariotomy” for the operation. Normal ovariotomy – a contradictio in terminis – was practised widely for several decades. Alfred Hegar (1830–1914), among many other gynaecologists, extended the indications of Battey's operation to include the treatment of various ovarian conditions as well, e.g., small tumors. Better insight into female physiology and ovarian function finally pushed the sinister operation of Robert Battey from the scene." European Journal of Obstetrics & Gynecology
December 1, 1998Volume 81, Issue 2, Pages 243–246 Battey's operation: an exercise in surgical frustration Michel Thiery Stichting Jan Palfyn, 1 Onderbergen, B-9000 Gent, Belgium DOI: http://dx.doi.org/10.1016/S0301-2115(98)00197-3 show
http://www.ejog.org/article/S0301-2115%2898%2900197-3/abstract
364 The history of Battey's operation - ovary removal. "Although Battey's operation continues to be performed (rarely) in cases of ovarian cancer or related pathology, its use in dealing with "troublesome" patients seems long over. Still, the long reign of Battey's operation should be an uncomfortable reminder of the dangers of medical fads and "innovative" treatments that seem like a good idea at the time." Providentia blog - Romeo Vittelli, PhD - May 02, 2010 Battey's Operation http://drvitelli.typepad.com/providentia/2010/05/batteys-operation.html
365 By 1880s, NY Women's Hospital, home to Sims and Battey, known for ovary removals. "The organs were removed without biopsy or even without being examined after extraction for evidence of disease." "May 1887, the ladies' board notified the Board of Governors that the (gynecological) operations being performed at the hospital were "very objectionable."" Mrs. Russell Sage: Women's Activism and Philanthropy in Gilded Age and ... By Ruth Crocker https://books.google.com/books?id=LMuZNdrCnKEC&pg=PA105&lpg=PA105&dq=mrs.+russell+sage+barbaric+surgery+ovaries+battey%27s&source=bl&ots=PnnLfEa044&sig=M4qYinYVmwrV1cpRzR8aQw-DbtI&hl=en&sa=X&ved=0CCwQ6AEwAGoVChMIhMm_ovnfxwIVig2SCh2HbwIT#v=onepage&q=mrs.%20russell%20sage%20barbaric%20surgery%20ovaries%20battey%27s&f=false
366 Battey's operation and the discovery (then sale of) hormones. The Estrogen Elixir: A History of Hormone Replacement Therapy in America By Elizabeth Siegel Watkins https://books.google.com/books?id=a15Vl2I-4NgC&pg=PT12&lpg=PT12&dq=the+estrogen+elixir+battey+ovaries+barbaric&source=bl&ots=q_aDgZ2jXI&sig=3tpSpcjvELJNsUmcRMLCKaZyMlU&hl=en&sa=X&ved=0CCEQ6AEwAGoVChMI_N3Hw_nfxwIVUYCSCh16kQbB#v=onepage&q=the%20estrogen%20elixir%20battey%20ovaries%20barbaric&f=false
367

4,294 of the 58,000 members completed the survey. Avg physician age was 51. 74% had had at least one lability claim against them. Avg number of claims was 2.6 per doctor. 41% were filed against them when they were residents. Avg age when claim filed was 36 yo. 48% reported claims were dropped or settled w/o payment. 36% reported a settlement payment made. Those that went to court or arbitration, 33% ended with payment made to plaintiff. Average paid on claims was $486,066. Highest for neuro impaired infants. Failure to diag breast cancer $420K.

Draft of the ACOG's review on personal medical liability. 'Delay or Failure to diagnose' made up 21.5% of all claims, 59.4% of those were for undiagnosed/misdiagnosed cancer. 39% of those were breast cancer; 15.9% were cervical; 15.9% were uterine; 15.9% were other; 12.2% was ovarian; 1.2 was fallopian. Patient injury - major: 28%; patient injury - minor: 23%;

DRAFT - 7/28 /15 Page 1 Overview of the 201 5 ACOG Survey on Professional Liability By Andrea M. Carpentieri, MA, James J. Lumalcuri, MSW , Jennie Shaw, MPH, and Gerald F. Joseph, Jr., MD, FACOG http://www.acog.org/-/media/Departments/Professional-Liability/2015PLSurveyNationalSummary.pdf?la=en
368 OBGYNs have less operative experience than in past and are not prepared when they move on to specialties. Those specializing in Gyn Oncology were evaluated by those they were training them. 40% attendings responded and 61% program directors. 49% reported fellows couldn't indep perform hysterectomy. 59% couldn't indep perform 30 min of a major procedure. 40% couldn't control bleeding. 58% couldn't dissect tissue planes. Lacked pathphysiology understanding. Deficient in protocol design - 54%; stat analysis - 54%; manuscript writing - 65%. The results suggest that general OBGYN residency is ineffective in preparing fellows for advanced training in Gyn Oncol and should prompt a revision of the goals and objectives of resident education. Gynecologic Oncology Reports - Preparedness of Ob/Gyn residents for fellowship training in gynecologic oncology David W. Doocorrespondenceemail , Matthew Powell , Akiva Novetsky , Jeanelle Sheeder , Saketh R. Guntupalli Open Access DOI: http://dx.doi.org/10.1016/j.gore.2015.03.004 | http://www.gynoncolreports.net/article/S2352-5789%2815%2900021-1/abstract
369

70% of ovarian cancers are caught in advanced stages. Cure rate less than 30%. Caught early, goes up to 75-90% cure rate. Dr. Lu results: Over 11 years of study. 4,051 post-menopausal participants. 2001-2011, had a baseline CA125 test done annually. 83.4% participants never had raised levels. 13.7% had increased levels but didn't need ultrasound. 2.9% that did need ultrasound. Of those, 10 indicated needed surgery, 4 of 10 had early stage ovarian cancer. One had endometrial cancer. Three had benign cysts. Two had ovarian tumors unlikely to become malignant. Women with ovarian cancer free of disease in 4 months to 42 months after treatment. UKCTOCS test also shows whether this was effective.

http://www.mdanderson.org/newsroom/news-releases/2013/ca-125-screening-tool-for-ovarian-cancer.html
The study was supported by the National Cancer Institute, and was a research project of MD Anderson’s ovarian cancer Specialized Program of Research Excellence (SPORE), NCI P50 CA83639, the Bioinformatics Shared Resources of MD Anderson CCSG NCI P30 CA16672, the National Foundation for Cancer Research. It has also received philanthropic funds from Golfers Against Cancer, the Tracy Jo Wilson Ovarian Cancer Foundation, the Mossy Foundation, the Norton family and Stuart and Gaye Lynn Zarrow. In addition to Lu, and Bast, other authors on the study include: Therese Bevers, M.D. Department of Clinical Cancer Prevention, Herbert Fritsche, Ph.D., Department of Laboratory Medicine, Deepak Bedi, M.D., Department of Diagnostic Radiology, Michael T. Deavers, M.D., Department of Pathology and Clinical Pathology; Charlotte Sun, Dr.PH, Department of Gynecologic Oncology, Mary A. Hernandez, Office of Translational Research, all with MD Anderson; Steven Skates, Ph.D., Massachusetts General Hospital and Harvard Medical School; Olasunkanmi Adeyinka, M.D., UT Physicians Family Physicians; William Newland, M.D., The Iowa Clinic; Richard Moore, M.D. and Cornelius Granai, M.D., both with Women & Infants Hospital, Brown University; Leroy Leeds, M.D., OGA Medical Center; Steven Harris, M.D., OB/GYN Associates of Dallas; Jeremy Geffen, M.D., Geffen Cancer Research Institute; and Nora Horick, Harvard Medical School and Massachusetts General Hospital.

As a co-inventor of the CA-125, Bast receives royalties from, and has served as an advisor to, Fujirebio Diagnostics, Inc.

LA Times, Ovarian cancer 'biomarker' screening works to find disease early August 27, 2013|By Melissa Healy http://articles.latimes.com/2013/aug/27/science/la-sci-ovarian-cancer-screening-20130826
370

Physicians may end up doing more procedures because they subconsciously are avoiding being idle.

Alix Spiegel

Which brings us, finally, to the subject, which incredibly, was never ever discussed during the nearly 20 years the doctors met: money. Specifically, the idea that doctors might be prescribing more visits and more procedures so that they could make more money. Frank Read and Bob Keller told me that this subject was completely verboten.

Bob Keller

We didn't want to talk about money. That's something that we wouldn't want to acknowledge because it would have been a show stopper. I mean it would have then gone right to the question of greed. And you're not going to keep a doc at the table if you say you're greedy.

Alix Spiegel

Doctors are uncomfortable acknowledging the role of money, but every doctor I talked to admitted, it affects medical decision-making. Including Gordon Smith, head of the Maine Medical Association.

Gordon Smith

Of course it does. That's just common sense. That's human nature. The payment system is an important influence.

Alix Spiegel

You see, the majority of doctors in this country are not on salary, but are paid for each thing they do: a la carte. That's what they mean when they say, fee for service. A phrase you've probably heard a lot.

And the way fee for service affects doctor behavior is clear. Gordon Smith.

Gordon Smith

If you pay people more the more things they do, they're going to do more things.

Alix Spiegel

Bob Keller points to his own specialty-- he's a back doctor-- and says one of the most popular operations among back doctors these days is this complicated procedure called an instrumented fusion.

When a patient has a back problem, the doctor can go in and insert metal rods. Keller says in the old days the doctor used a much simpler and safer operation, but the new, more complicated one costs more.

Bob Keller

Surgeons could charge more because they were doing these complicated procedures, and so they were putting the screws in. They billed for putting the screws. They were putting the plates in, they billed for putting the plates in. Doing all these things. In the old days a fusion was very much a simpler operation with no external devices. It was all done with the patient's own tissues and bone. So you had a whole new high-tech procedure that was enormously attractive to spine surgeons. And it literally took off in this country.

At the same time, as most good spine surgeons will admit, they had no research to support what they were doing.

Alix Spiegel

In fact, says Keller, the one high quality study that did exist wasn't so positive.

Bob Keller

It showed that it isn't so great actually, as people thought it was. And they also showed that interestingly enough, that the old fashioned non-instrumented fusion was as successful as the instrumented fusion. Which was a real blow.

Alix Spiegel

And here in miniature is one of the big problems with the way our current system is set up. It's a problem some call, more is not better. Doctors exist in a system that encourages-- and really because of their fear of malpractice suits-- actually forces them to do more. More surgery, more tests, more stuff of every kind. And while most Americans just assume that more care is good, it turns out that more isn't always better for patients. Because every time you get a medical procedure, you risk the possibility of complications and doctor error.

 

This American Life - 391: More Is Less Transcript Originally aired 10.09.2009 Note: This American Life is produced for the ear and designed to be heard, not read. We strongly encourage you to listen to the audio, which includes emotion and emphasis that's not on the page. Transcripts are generated using a combination of speech recognition software and human transcribers, and may contain errors. Please check the corresponding audio before quoting in print. © 2009 Ira Glass http://www.thisamericanlife.org/radio-archives/episode/391/transcript
371 Hysterectomy second most common surgery in the US. 6-fold higher than some other Western countries. Study by NHDS (sampling system has changed) found that rates vary greatly among regions and are higher when performed by male surgeon and in black women. "Professional uncertainty about appropriate use is the primary cause for the high rate." "Few data to support hysterectomy for leiomyoma." "No evidence to support removal to avoid future symptoms." Indications for Hysterectomy Karen J. Carlson, David H. Nichols, and Isaac Schiff N Engl J Med 1993; 328:856-860March 25, 1993DOI: 10.1056/NEJM199303253281207

http://www.nejm.org/doi/full/10.1056/NEJM199303253281207

 

372

There has been remarkably little investigation into the long-term outcomes of hysterectomy, particularly given its widespread use. Women are only tracked for a year afterward, typically. "Hysterectomy remains a one-size-fits-all remedy for gynecologic conditions, despite its clear limitations. It is critical to continue to develop better alternatives to hysterectomy and to investigate its longterm consequences as well as those of its alternatives."

Attention became focused on the overuse of hysterectomy during the 1990s, when the Agency for Healthcare Research and Quality sponsored research and conferences on this topic. These forums highlighted the fact that there were clear differences in hysterectomy rates based on a variety of nonmedical factors including the geographic location of the patient, the race of the patient, and the sex of the gynecologist performing the surgery. Both scientific and lay publications continue to discuss this important issue. Yet despite intensive assessment, the rate of hysterectomy continues to be high, with only a small decline happening in the last few years.

"Most hysterectomies are elective. Uterine leiomyomas (uterine fibroids) are cited as the most common indication for hysterectomy, accounting for approximately one-third of all hysterectomies performed. 2 Abnormal uterine bleeding is the next most common indication, accounting for approximately 16% of hysterectomies, while gynecologic cancers account for less than 8% of all hysterectomies.2 Fibroids and abnormal uterine bleeding thus account for five times as many hysterectomies as all gynecologic cancers combined. Interestingly, these are the two indications for which we have made the most progress in developing alternative treatments."

"The rationale for elective BSO at the time of hysterectomy has been twofold: BSO would decrease the risk of ovarian cancer, and once a woman reached menopause, her ovaries were no longer hormonally active and, thus, no longer useful. Both suppositions are flawed. First, research has shown that hysterectomy with BSO puts women at greater risk for mortality from conditions and diseases far more common than ovarian cancer. Although ovarian cancer can be difficult to diagnose, it is a relatively rare disease. When considering mortality risk for more common diseases including coronary artery disease and hip fracture, a decision analysis model favored retention of the ovaries until at least age 65 for women with an average risk for ovarian cancer.18 Similarly, in a large nationwide cohort study, hysterectomy alone performed in women younger than 50 years of age increased the risk of cardiovascular disease later in life, and there was additional risk among those who undergo oophorectomy.11 Second, the notion that the ovaries are no longer useful after menopause has been shown to be flawed as well. Although ovarian estrogen production plummets after menopause, the ovaries continue to make substantial amounts of androgens.12 These ovarian androgens undergo peripheral conversion to estrogens and may have direct beneficial effects on mood and libido.12 Recent REP studies have focused attention on the long-term risks of removal of the ovaries with or without hysterectomy.15,16,19,20"

"Hysteroscopic myomectomy is performed when fibroids are located within the endometrial cavity or extend less than 50% into the myometrium. This procedure is safe for women who want future pregnancies and is sometimes employed when infertility or recurrent miscarriage is the primary or sole fibroid symptom. If the fibroid is intramural, or if the uterus is structurally normal, an endometrial ablation may help control bleeding. With this technique, the endometrium is destroyed using an instrument placed inside the uterus. Endometrial ablation should not be done for women who want future pregnancies and may not be optimal for women at high risk for endometrial cancer, since 100% destruction of the endometrium is not guaranteed. Although this procedure originally required advanced surgical skills, newer devices allow general gynecologists to perform it."

Minn Med. Author manuscript; available in PMC 2013 Oct 21. Published in final edited form as: Minn Med. 2012 Mar; 95(3): 36–39. PMCID: PMC3804006 NIHMSID: NIHMS383629 Reassessing Hysterectomy Elizabeth A. Stewart, M.D., Lynne T. Shuster, M.D., and Walter A. Rocca, M.D., M.P.H. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804006/
373 Doctors respond to the 1993 Carlson, Nichols, Schiff NEJM article, Indications for hysterectomy - the first points out that the risks of ovarian failure are severe and that hysterectomy likely increases those risks, which she felt should have been called out with greater emphasis in the article. July 1993 responses to authors of citation 371. http://www.nejm.org/doi/pdf/10.1056/NEJM199307223290411
374

NOTE: This is not what it appears, in that this is only based on inpatient stats. The number of outpatient hysterectomies increased from 9% in 2003 to 39% in 2012, rendering a 1.9% decrease in inpatient hysterectomies hardly significant.

"Hysterectomy rates significantly decreased 1.9% per year between 1997 and 2005 (-0.5% for ages 18-44, -3.1% for ages 45-64, and -5.0% for ages 65 years and older). The estimated annual decrease in rates was significant in the Northeast (-2.9%), Northwest (-1.7%), and South (-2.6%), but not in the West. For hysterectomies performed among women ages 18-44 years, the percentage in 1997-98 compared with 2004-05 resulting from leiomyoma (fibroids) decreased (31.4% vs. 26.9%), from uterine bleeding increased (14.6% vs. 25.2%), from endometriosis decreased (17.3% in vs. 16.2%), and from pain increased (10.4% vs. 11.7%); the most common procedure, total abdominal hysterectomy, decreased (65.0% vs. 60.5%), the second most common procedure, vaginal hysterectomy, decreased (32.0% vs. 30.7%), and the third most common procedure, subtotal hysterectomy, increased (1.6% in 1997-98 and 7.5% in 2004-05). Decreases in hysterectomy rates occurred for most of the reproductive health conditions resulting in hysterectomy. Exceptions included pain and bleeding in the age group 18-44 and bleeding in the age group 45-64. An increase occurred in subtotal abdominal hysterectomy rates in each of the age groups."

Med Sci Monit. 2008 Jan;14(1):CR24-31. Hysterectomy surveillance in the United States, 1997 through 2005. Merrill RM1.

http://www.ncbi.nlm.nih.gov/pubmed/18160941

to verify that NHDS data is inpatient only, see this: http://www.cdc.gov/nchs/data/series/sr_13/sr13_168.pdf

375 TCRE for heavy bleeding instead of hysterectomy is associated with a 2.31 OR of having a urinary infection:

"There were significantly more hospital referrals for UI in the TAH group compared with the TCRE group (46 [15%] versus 16 [7%]; OR 2.27, 95% CI 1.25–4.12). More women were referred for urological investigations after a TAH than after a TCRE (39 [12%] versus 13 [6%], 95% CI for the difference in proportions 2–11%). A higher, but statistically nonsignificant, proportion of women had objectively demonstrated UI after a TAH than after a TCRE (25 [8%] versus 10 [4%], 95% CI for the difference in proportions –1 to 8%). There were a greater number of hospital referrals for treatment of UI in the TAH group (36, 11%) than in the TCRE group (12, 5%), 95% CI for the difference in proportions (1–11%). After adjusting for age, weight, smoking status and mode of delivery, the increased rate of hospital referral for UI after TAH remained, with an odds ratio of 2.31, 95% CI 1.24–4.30. Conclusions TAH is associated with a significantly increased incidence of hospital referral for UI, urological investigations and treatment for UI at 10 years of follow up compared with TCRE"
BJOG, Comparison of the long-term effects of simple total abdominal hysterectomy with transcervical endometrial resection on urinary incontinence S Allahdin, a K Harrild, b QA Warraich, a C Bain a a Department of Obstetrics and Gynaecology, Aberdeen Royal Infirmary, Aberdeen, UK b Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen, UK Correspondence: Dr S Allahdin, Department of Obstetrics and Gynaecology, Aberdeen Royal Infirmary, Aberdeen, AB25 2ZA, UK. Email drallahdin@hotmail.co.uk Accepted 10 September 2007. Published OnlineEarly 26 October 2007 http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2007.01546.x/pdf
376 Hysterectomy, oophorectomy, and dementia risk:

"When stratified by age at dementia diagnosis, hysterectomy was associated with an increased risk for early-onset dementia before the age of 50: hysterectomy alone (RR = 1.38, 95% confidence interval (CI) = 1.07-1.78), with unilateral oophorectomy (RR = 2.10, 95% CI = 1.28-3.45), with bilateral oophorectomy (RR = 2.33, 95% CI = 1.44-3.77). The younger the age at hysterectomy/oophorectomy, the greater was the risk."
Dement Geriatr Cogn Disord. 2010;30(1):43-50. doi: 10.1159/000314681. Epub 2010 Jul 30. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Phung TK1, Waltoft BL, Laursen TM, Settnes A, Kessing LV, Mortensen PB, Waldemar G. http://www.ncbi.nlm.nih.gov/pubmed/20689282
377 "Medical and surgical practices have evolved during history as a result of the transformation of medical concepts and theories. Bilateral oophorectomy performed electively at the time of hysterectomy for a benign indication is now under scrutiny and critical reappraisal because long-term risks may outweigh the benefits in the majority of women. Like the removal of any other healthy organ for the prevention of possible future diseases (e.g., appendix, tonsils, or breasts), bilateral oophorectomy must follow the principle “primun non nocere, or first do no harm.”" Oophorectomy for whom and at what age? Primum non nocere Walter A. Rocca Division of Epidemiology, Department of Health Sciences Research, and Department of Neurology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Lian G. Ulrichemail Department of Gynecology and Obstetrics, Copenhagen University Hospital “Rigshospitalet”, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Received: October 14, 2011; Published Online: October 31, 2011 http://www.maturitas.org/article/S0378-5122%2811%2900356-2/abstract
378 "AIMS: Hysterectomy for benign indications is one of the commonest surgical procedures in women, but the association between the procedure and cardiovascular disease (CVD) is not fully understood. In this population-based cohort study, we studied the effects of hysterectomy, with or without oopherectomy, on the risk of later life CVD. METHODS AND RESULTS: Using nationwide healthcare registers, we identified all Swedish women having a hysterectomy on benign indications between 1973 and 2003 (n = 184,441), and non-hysterectomized controls (n = 640,043). Main outcome measure was the first hospitalization or death of incident CVD (coronary heart disease, stroke, or heart failure). Occurrence of CVD was determined by individual linkage to the Inpatient Register. In women below age 50 at study entry, hysterectomy was associated with a significantly increased risk of CVD during follow-up [hazard ratio (HR), 1.18, 95% confidence interval (CI), 1.13-1.23; HR, 2.22, 95% CI, 1.01-4.83; and HR, 1.25, 95% CI, 1.06-1.48; in women without oopherectomy, with oopherectomy before or at study entry, respectively, using women without hysterectomy or oopherectomy as reference]. In women aged 50 or above at study entry, there were no significant associations between hysterectomy and incident CVD. CONCLUSIONS: Hysterectomy in women aged 50 years or younger substantially increases the risk for CVD later in life and oopherectomy further adds to the risk of both coronary heart disease and stroke." Eur Heart J. 2011 Mar;32(6):745-50. doi: 10.1093/eurheartj/ehq477. Epub 2010 Dec 24. Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Ingelsson E1, Lundholm C, Johansson AL, Altman D. http://www.ncbi.nlm.nih.gov/pubmed/21186237
379 RESULTS: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of parkinsonism compared with referent women (HR 1.68; 95% CI 1.06 to 2.67; p = 0.03), and the risk increased with younger age at oophorectomy (test for linear trend; p = 0.01). The findings were similar regardless of the indication for the oophorectomy, and for unilateral or bilateral oophorectomy considered separately. The findings were also consistent for Parkinson disease alone, but did not reach significance. Neurology. 2008 Jan 15;70(3):200-9. Epub 2007 Aug 29. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Rocca WA1, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd. http://www.ncbi.nlm.nih.gov/pubmed/17761549
380 Ovarian blood flow due to shared artery impact of hysterectomy on ovaries J Soc Gynecol Investig. 2005 Jan;12(1):54-7. Ovarian changes after abdominal hysterectomy for benign conditions. Chan CC1, Ng EH, Ho PC. http://www.ncbi.nlm.nih.gov/pubmed/15629673
381 Over 5 years after hysterectomy, women with only one ovary reached menopause 4.4 years earlier than those with both who had hysterectomy. Women who had hysterectomy were 3x as likely to go through menopause in the subsequent 5 years. BJOG. 2005 Jul;112(7):956-62. The association of hysterectomy and menopause: a prospective cohort study. Farquhar CM1, Sadler L, Harvey SA, Stewart AW. http://www.ncbi.nlm.nih.gov/pubmed/15957999
382 UAE alternative - embolization for fibroids. RESULTS: Four randomized controlled trials with a total of 515 patients were included. On the short-term, uterine artery embolization showed fewer blood loss, shorter hospital stay, and quicker resumption of work. Mid- and long-term results showed comparable health-related quality of life results and a higher reintervention rate in the uterine artery embolization group, whereas both groups were equally satisfied. CONCLUSION: Uterine artery embolization has short-term advantages over surgery. On the mid- and long-term the benefits were similar, except for a higher reintervention rate after uterine artery embolization. Am J Obstet Gynecol. 2011 Oct;205(4):317.e1-18. doi: 10.1016/j.ajog.2011.03.016. Epub 2011 Mar 16. Uterine artery embolization versus surgery in the treatment of symptomatic fibroids: a systematic review and metaanalysis. van der Kooij SM1, Bipat S, Hehenkamp WJ, Ankum WM, Reekers JA. http://www.ncbi.nlm.nih.gov/pubmed/21641570
383 UAE and hysterectomy affect ovaries equally Hum Reprod. 2007 Jul;22(7):1996-2005. Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy. Hehenkamp WJ1, Volkers NA, Broekmans FJ, de Jong FH, Themmen AP, Birnie E, Reekers JA, Ankum WM. http://www.ncbi.nlm.nih.gov/pubmed/17582145
384 Outcomes of focused ultrasound surgery to treat fibroids Fertil Steril. 2006 Jan;85(1):22-9. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Stewart EA1, Rabinovici J, Tempany CM, Inbar Y, Regan L, Gostout B, Hesley G, Kim HS, Hengst S, Gedroyc WM. http://www.ncbi.nlm.nih.gov/pubmed/16412721
385 Oophorectomy rate may actually be 73% that of the rate of hysterectomy. "As recently as 2006, data showed that the rate of oophorectomy or salpingo-oophorectomy either alone or with hysterectomy was approximately 73% of the rate of hysterectomy" Minn Med. Author manuscript; available in PMC 2013 Oct 21. Published in final edited form as: Minn Med. 2012 Mar; 95(3): 36–39. PMCID: PMC3804006 NIHMSID: NIHMS383629 Reassessing Hysterectomy Elizabeth A. Stewart, M.D., Lynne T. Shuster, M.D., and Walter A. Rocca, M.D., M.P.H.

http://www.cdc.gov/nchs/data/series/sr_13/sr13_168.pdf

and

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804006/

386 (DM note: my connection to fibromyalgia is being substantiated - exciting and sad, at once) J Pain Res. 2015 Aug 20;8:561-9. doi: 10.2147/JPR.S86573. eCollection 2015. Assessing the prevalence of autoimmune, endocrine, gynecologic, and psychiatric comorbidities in an ethnically diverse cohort of female fibromyalgia patients: does the time from hysterectomy provide a clue? Brooks L1, Hadi J2, Amber KT1, Weiner M3, La Riche CL4, Ference T1. http://www.ncbi.nlm.nih.gov/pubmed/26316807
387 Fibromyalgia and hysterectomy/estrogen Clin Rheumatol. 2013 Jul;32(7):975-81. doi: 10.1007/s10067-013-2212-8. Epub 2013 Feb 16. Age-of-onset of menopause is associated with enhanced painful and non-painful sensitivity in fibromyalgia. Martínez-Jauand M1, Sitges C, Femenia J, Cifre I, González S, Chialvo D, Montoya P. http://www.ncbi.nlm.nih.gov/pubmed/23417348
388 Where ovarian blood supply originates. This is important in terms of the effect of hysterectomy on the continued viability of the ovaries.

"Generally the ovarian arteries arise from the ventral surface of the aorta in approximately 83% of cases, usually as a single origin but they may have multiple origins.[18] In 17% of cases, the ovarian arteries may arise from the renal arteries or other pelvic vessels. The blood supply to the ovaries comprises flow from the uterine artery from branches that create a tubal and ovarian arterial arcade and anastomose with the lateral tubal and ovarian branches from the ovarian artery. In 40% of cases, the ovarian artery solely supplies the ovary while there is a shared supply with the uterine artery in 30% of cases. In 10% of patients, the uterine artery is the main supply to the ovaries. The uterine artery supplies the fallopian tube in 60% of patients while there is shared supply in another 56% of cases. In only 4% of cases does the ovarian artery solely supply the fallopian tube.[17,18] Knowledge of these anastomoses is important since they provide for the collateral blood flow that may result in the failure of percutaneous embolization or ovarian nontarget embolization."
Applied Radiology Uterine Fibroid Embolization for the Treatment of Symptomatic Leiomyomata Maxim Itkin, MD, Richard Shlansky-Goldberg, MD Disclosures Appl Radiol. 2002;31(10) http://www.medscape.com/viewarticle/444054_4
389 UAE / UFE for the treatment of fibroids can lead to ovarian failure. Myomectomy should be considered and women should be warned that this is possible. Transient ovarian failure: a complication of uterine artery embolization Paula Amato, M.D.correspondenceemail , Anne C Roberts, M.D. Received: March 1, 2000; Received in revised form: July 31, 2000; Accepted: July 31, 2000; DOI: http://dx.doi.org/10.1016/S0015-0282(00)01678-2 http://www.fertstert.org/article/S0015-0282%2800%2901678-2/fulltext?refuid=S1074-3804%2805%2960189-2&refissn=1074-3804
390 A meta-analysis of the benefits of prophylactic bilateral oophorectomy. Though a number of variables make specificity difficult, best estimates indicate that ovarian cancer risk is reduced 80% and breast cancer is reduced 50% for combined BRCA 1 and 2. SHIVA - A Next-Generation Trial Disappoints, Provides Insights Fallout After Fata: Loss of Trust in Physicians Treating Cancer Patients: 'Letting It Hurt the Proper Amount' Sex After Cancer: The Unaddressed Issue Journal of the National Cancer Institute Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-Oophorectomy in BRCA1 or BRCA2 Mutation Carriers Timothy R. Rebbeck; Noah D. Kauff; Susan M. Domchek Disclosures J Natl Cancer Inst. 2009;101(2):80-87. http://www.medscape.com/viewarticle/587249_4
391 Hysterectomy in Denmark - 16% of population by equal to or greater age 65. Acta Oncologica Volume 54, Issue 8, 2015 Hysterectomy and its impact on the calculated incidence of cervical cancer and screening coverage in Denmark Epidemiology Hysterectomy and its impact on the calculated incidence of cervical cancer and screening coverage in Denmark Preview Full text HTML PDF Access options DOI: 10.3109/0284186X.2015.1016625 Janni Uyen Hoa Lama*, Elsebeth Lyngea, Sisse Helle Njora & Matejka Rebolja pages 1136-1143 http://www.tandfonline.com/doi/abs/10.3109/0284186X.2015.1016625?journalCode=ionc20
392

Study that calls BSO a success. So, to prevent 33 incremental women from getting peritoneal or ovarian cancer, 30,614 had to lose their ovaries. That's 928 women to prevent cancer in 1 woman. Of the 56,692 in the study, 57 were diag with cancer. If the BSO risk reduction is applied to the hsyterectomy group, the new number of women diag would be 90. So, rather than the risk being 1/10 of 1%, the risk would still be less than 2/10 of 1% (0.16%). This is absurd.

"Of 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).

CONCLUSIONS:

The removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation."

Obstet Gynecol. 2014 Jan;123(1):65-72. doi: 10.1097/AOG.0000000000000061. Ovarian cancer rates after hysterectomy with and without salpingo-oophorectomy. Chan JK1, Urban R, Capra AM, Jacoby V, Osann K, Whittemore A, Habel LA. http://www.ncbi.nlm.nih.gov/pubmed/24463665
393 Role of HPG axis in rheumatoid arthritis Baillière's Clinical Rheumatology Volume 10, Issue 2, May 1996, Pages 295–332 Neuroendocrine Immune Mechanisms of Rheumatic Diseases Cover image Perturbations of hypothalamic-pituitary-gonadal (HPG) axis and adrenal androgen (AA) functions in rheumatoid arthritis Alfonse T. Masi, José António P. Da Silva, Maurizio Cutolo http://www.sciencedirect.com/science/article/pii/S0950357996800197
394 Interrelation of HPG and HPA axes University of New Orleans Scholar Works@UNOUniversity of New Orleans Theses and Dissertations Dissertations and Theses 12-20-2013 Coupling of the HPA and HPG Axes Andrew DismukesUniversity of New Orleans http://scholarworks.uno.edu/cgi/viewcontent.cgi?article=2822&context=td
395 RESULT(S): Quantitatively, women secrete greater amounts of androgen than of estrogen. The major circulating steroids generally classified as androgens include dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone in descending order of serum concentration, though only the latter two bind the androgen receptor. The other three steroids are better considered as pro-androgens. Dehydroepiandrosterone is primarily an adrenal product, regulated by adrenocorticotropic hormone (ACTH) and acting as a precursor for the peripheral synthesis of more potent androgens. Dehydroepiandrosterone is produced by both the ovary and adrenal, as well as being derived from circulating DHEAS. Androstenedione and testosterone are products of the ovary and the adrenal. Testosterone circulates both in its free form, and bound to protein including albumin and sex steroid hormone-binding globulin (SHBG), the levels of which are an important determinant of free testosterone concentration. CONCLUSION(S): The postmenopausal ovary is an androgen-secreting organ and the levels of testosterone are not directly influenced by the menopausal transition or the occurrence of menopause. Dihydrotestosterone (DHT) is primarily a peripheral product of testosterone metabolism. Severe androgen deficiency occurs in hypopituitarism, but other causes may lead to androgen deficiency, including Addison's disease, corticosteroid therapy, chronic illness, estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone), premenopausal ovarian failure, or oophorectomy. Fertil Steril. 2002 Apr;77 Suppl 4:S3-5. Androgen production in women. Burger HG1. http://www.ncbi.nlm.nih.gov/pubmed/12007895
396 The age at ovarian failure was determined in 90 women who had previously undergone abdominal hysterectomy with bilateral ovarian conservation and in 226 women who had undergone a spontaneous menopause. The mean age of ovarian failure in the hysterectomized group was 45.4 +/- 4.0 years (standard deviation), and this was significantly lower than the mean age of 49.5 +/- 4.04 years in the nonhysterectomized control group (P less than 0.001). There was a significant correlation between the age at hysterectomy and the age of ovarian failure in the women who were 44 years or less at the time of ovarian failure (r = 0.62, P less than 0.001), implying a causal relationship. The indication for hysterectomy did not influence the time of ovarian failure. Two explanations are proposed as to how conventional surgery for hysterectomy may adversely affect ovarian function. Fertil Steril. 1987 Jan;47(1):94-100. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function and literature review. Siddle N, Sarrel P, Whitehead M. http://www.ncbi.nlm.nih.gov/pubmed/3539646
397 Honesty with patients. 2009 survey of 1,891 practicing physicians "Overall, approximately one-third of physicians did not completely agree with disclosing serious medical errors to patients, almost one-fifth did not completely agree that physicians should never tell a patient something untrue, and nearly two-fifths did not completely agree that they should disclose their financial relationships with drug and device companies to patients. Just over one-tenth said they had told patients something untrue in the previous year."

Healthaffairs.org

Survey Shows That At Least Some Physicians Are Not Always Open Or Honest With Patients Lisa I. Iezzoni,*, Sowmya R. Rao, Catherine M. DesRoches3, Christine Vogeli, and Eric G. Campbell

doi: 10.1377/hlthaff.2010.1137 Health Aff February 2012 vol. 31 no. 2 383-391

http://content.healthaffairs.org/content/31/2/383.abstract
398 American women are four times more likely to die during or immediately after pregnancy than are women in Scandinavia, Japan, Ireland, and Slovakia, among other countries. WHO - Trends in maternal mortality: 1990 to 2008 Estimates developed by WHO, UNICEF, UNFPA and The World Bank Share Print Authors: World Health Organization, UNICEF, UNFPA and The World Bank Image of cover Publication details Publication date: 2010 Languages: English, French ISBN: 978 92 4 150026 5 http://www.who.int/reproductivehealth/publications/monitoring/9789241500265/en/
399 From the entire sample, 1083 subjects were finally included. The mean score on the B-PFSF© was 15.9 and a total of 74.4% of the patients presented total scores lower or equal to 20, indicating the risk of presenting with HSDD (hypoactive sexual desire disorder). The possibility to be at risk of HSDD increased with age from 65.9% in the age group <45 years old to 76.6% in the age group ≥55 years old. Non-users of hormone replacement therapy presented a higher risk of HSDD (odds ratio 2.1; 95% confidence interval 1.3–3.4); the risk was increased as well when the time elapsed since surgical menopause was <5 years (odds ratio 1.8; 95% confidence interval 1.0–3.0). Climacteric Volume 12, Issue 6, 2009 Translator disclaimer Risk of hypoactive sexual desire disorder and associated factors in a cohort of oophorectomized women Original Article Risk of hypoactive sexual desire disorder and associated factors in a cohort of oophorectomized women DOI: 10.3109/13697130903075345 C. Castelo-Branco*a, S. Palaciosb, J. Combaliac, M. Ferrerd & G. Traveriad pages 525-532 http://www.tandfonline.com/doi/full/10.3109/13697130903075345
400 Review of understanding of inhibin and activin behavior in the ovary and its use to test for ovarian cancer REVIEW Inhibin/activin and ovarian cancer D M Robertson, H G Burger and P J Fuller Endocrine-Related Cancer (2004) 11 35–49 http://erc.endocrinology-journals.org/content/11/1/35.full.pdf
401 Activin, inhibin (and follistatin) levels don't alter with age Serum inhibin, activin and follistatin in postmenopausal women with epithelial ovarian carcinoma Usha Menon Lecturer1,*, Simon C. Riley Lecturer2, Janice Thomas Statistician3, Chinmoy Bose Clinical Research Fellow1, Anne Dawnay Senior Lecturer4, Lee W. Evans Senior Lecturer5, Nigel P. Groome Professor5 andIan J. Jacobs Professor1 Article first published online: 12 AUG 2005 DOI: 10.1111/j.1471-0528.2000.tb11102.x Issue BJOG: An International Journal of Obstetrics & Gynaecology BJOG: An International Journal of Obstetrics & Gynaecology Volume 107, Issue 9, pages 1069–1074, September 2000 http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2000.tb11102.x/full
402 Cartilage is a sex hormone sensitive tissue. Women without ovaries at risk for osetoarthritis. Clinical Orthopaedics & Related Research: December 1986 Article: PDF Only Estrogens and Osteoarthritis. ROSNER, ITZHAK A. M.D.; GOLDBERG, VICTOR M. M.D.; MOSKOWITZ, ROLAND W. M.D. http://journals.lww.com/corr/Abstract/1986/12000/Estrogens_and_Osteoarthritis.10.aspx
403 Importance of gonadal hormones in rheumatoid arthritis Baillière's Clinical Rheumatology Volume 6, Issue 1, February 1992, Pages 193–219 The Course and Outcome of Rheumatoid Arthritis Cover image The effects of gender and sex hormones on outcome in rheumatoid arthritis J.A.P. Da Silva, G.M. Hall http://www.sciencedirect.com/science/article/pii/S0950357905803449
404 Anecdotal experience with autoimmune disorders after hyster/ooph HysterSisters - Reload this Page Curious - who developed auto-immune diseases after hysterectomy or oophorectomy? http://www.hystersisters.com/vb2/showthread.php?t=425570
407 Autoimmune and hormones connection Lahey - Autoimmune Disease and Women by Mary Calvagna, MS https://lahey.org/Departments_and_Locations/Departments/Gynecology/Ebsco_Content/Oophorectomy.aspx?chunkiid=14685
408 Arthritis and estrogen connection The role of estrogen and oophorectomy in immune synovitis V.M. Goldberg , R.W. Moskowitz , I. Rosner , C. Malemud Department of Orthopaedic Surgery and Division of Rheumatology, Case Western Reserve University, Cleveland, Ohio, USA http://www.semarthritisrheumatism.com/article/0049-0172%2881%2990076-7/abstract
409 Role of the HPA and HPG axes in rheumatism and autoimmune disorders Ann N Y Acad Sci. 2000;917:835-43. The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis. Cutolo M1, Villaggio B, Foppiani L, Briata M, Sulli A, Pizzorni C, Faelli F, Prete C, Felli L, Seriolo B, Giusti M. http://www.ncbi.nlm.nih.gov/pubmed/11268413
410 Interrelation and roles of HPA and HPG axes in CFS and fibromyalgia Arthritis Research & Therapy,
Cortisol and hypothalamic–pituitary–gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones Ali Gur1*, Remzi Cevik1, Kemal Nas1, Leyla Colpan2 and Serdar Sarac3 * Corresponding author: Ali Gur alig@dicle.edu.tr Author Affiliations 1 Department of Physical Medicine and Rehabilitation, School of Medicine, Dicle University, Diyarbakır, Turkey 2 Department of Biochemistry, School of Medicine, Dicle University, Diyarbakır, Turkey 3 Department of Physical Medicine and Rehabilitation, Kartal State Hospital, Istanbul, Turkey For all author emails, please log on. Arthritis Res Ther 2004, 6:R232-R238 doi:10.1186/ar1163
http://www.arthritis-research.com/content/6/3/r232
411 HPG and HPG intimately linked and play crucial role in autoimmune disorders. Play important roles in regulation of inflammation and predisposition to autoimmune disorders. The Immune-Neuroendocrine Circuitry: History and Progress edited by I. Berczi, Andor Szentivanyi https://books.google.com/books?id=dbAFZwc0FkkC&pg=PA508&lpg=PA508&dq=HPG+arthritis&source=bl&ots=pHBMXvbJoD&sig=E3wg_38BfP1MdOSyD5ati7HTQLY&hl=en&sa=X&ved=0CCMQ6AEwATgKahUKEwjS87SNk5jIAhVFmYAKHTPCC0c#v=onepage&q=HPG%20arthritis&f=false
412 The immune / endocrine system and nervous system maintain extensive communication. J Neurol. 2007 May;254 Suppl 2:II8-11. Psychoneuroimmunology--cross-talk between the immune and nervous systems. Ziemssen T1, Kern S. http://www.ncbi.nlm.nih.gov/pubmed/17503136
413 This review demonstrates growing evidence for the hypothesis that endocrine factors from the pituitary and hypothalamus directly influence the development and function of the immune system. Klin Wochenschr. 1986 Jan 2;64(1):1-7. Endocrine regulation of the immune system. Kiess W, Belohradsky BH. http://www.ncbi.nlm.nih.gov/pubmed/3512901
414 Activin A (gonads make this) responsible for neurogenesis following neurodegeneration. The protein the gonads make is needed for our brains to regenerate after harm. Stem Cells. 2009 Jun; 27(6): 1330–1346. doi: 10.1002/stem.80 PMCID: PMC2733378 Activin A Is Essential for Neurogenesis Following Neurodegeneration Andrea Abdipranoto-Cowley,a,b Jin Sung Park,a David Croucher,c James Daniel,a,b Susan Henshall,2,c Sally Galbraith,d Kyle Mervin,a and Bryce Vissela,b http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733378/
415 Activin A tied to autoimmune disease J Autoimmun. 2006 Feb;26(1):37-41. Epub 2005 Dec 5. Suppression of activin A in autoimmune lung disease associated with anti-GM-CSF. Bonfield TL1, Barna BP, John N, Malur A, Culver DA, Kavuru MS, Thomassen MJ. http://www.researchgate.net/publication/7432817_Suppression_of_activin_A_in_autoimmune_lung_disease_associated_with_anti-GM-CSF
416 Activin A promotes proliferation of lung and vascular smooth muscle cells and premyocardial cells (28–30) The Leydig Cell in Health and Disease edited by Anita H. Payne, Matthew P. Hardy https://books.google.com/books?id=x4ttqKIAOg0C&pg=PA324&lpg=PA324&dq=activin+lung+health&source=bl&ots=vVxXQzwDZw&sig=-G-p-3gsGEXTMrAlm9ULfAO1pNA&hl=en&sa=X&ved=0CFgQ6AEwCWoVChMIyqG59ZeYyAIVBZmACh3VLgFn#v=onepage&q=activin%20lung%20health&f=false
417 Connection between the central nervous system and IBS / gut disorders Gut 2000;47:iv78-iv80 doi:10.1136/gut.47.suppl_4.iv78 Chapter 7 The autonomic nervous system in functional bowel disorders G Tougas http://gut.bmj.com/content/47/suppl_4/iv78.full
418 Cytokines are not simply immune, but rather neuro-immune modulators. (Cytokines are tied to all kinds of issues incl Alzheimer's and Parkinson's as well as cancer and arthritis.) Neuroscience - Neuro-Immune Crosstalk https://www.neurorelief.com/?p=cms&cid=96&pid=87
419 Proteomic analysis has previously shown that activin A, a member of the transforming growth factor beta family, is produced by human articular cartilage. This study was undertaken to investigate whether activin A affects cartilage matrix catabolism and how its production is regulated. Arthritis Rheum. 2007 Nov;56(11):3715-25. Activin A is an anticatabolic autocrine cytokine in articular cartilage whose production is controlled by fibroblast growth factor 2 and NF-kappaB. Alexander S1, Watt F, Sawaji Y, Hermansson M, Saklatvala J. http://www.ncbi.nlm.nih.gov/pubmed/17968943
420 Oophorectomy and myocardial infarction - heart J Clin Epidemiol. 2000 Aug;53(8):832-7. Risk of myocardial infarction after oophorectomy and hysterectomy. Falkeborn M1, Schairer C, Naessén T, Persson I. http://www.ncbi.nlm.nih.gov/pubmed/10942866
421

No benefit. No breast cancer risk reduction for women who have an oophorectomy.

RESULTS: Applying the four previously described analytical methods and the data of 551 to 934 BRCA1/2 mutation carriers with a median follow-up of 2.7 to 4.6 years, the odds ratio was 0.61 (95% confidence interval [CI] = 0.35 to 1.08), and the hazard ratios were 0.36 (95% CI = 0.25 to 0.53), 0.62 (95% CI = 0.39 to 0.99), and 0.49 (95% CI = 0.33 to 0.71), being similar to earlier findings. For the revised analysis, we included 822 BRCA1/2 mutation carriers. After a median follow-up period of 3.2 years, we obtained a hazard ratio of 1.09 (95% CI = 0.67 to 1.77). CONCLUSION: In previous studies, BC risk reduction after RRSO in BRCA1/2 mutation carriers may have been overestimated because of bias. Using a design that maximally eliminated bias, we found no evidence for a protective effect.

J Natl Cancer Inst. 2015 Mar 18;107(5). pii: djv033. doi: 10.1093/jnci/djv033. Print 2015 May. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. Heemskerk-Gerritsen BA1, Seynaeve C1, van Asperen CJ1, Ausems MG1, Collée JM1, van Doorn HC1, Gomez Garcia EB1, Kets CM1, van Leeuwen FE1, Meijers-Heijboer HE1, Mourits MJ1, van Os TA1, Vasen HF1, Verhoef S1, Rookus MA1, Hooning MJ1; Hereditary Breast and Ovarian Cancer Research Group Netherlands. http://www.ncbi.nlm.nih.gov/pubmed/25788320
422 CONCLUSIONS: Approximately 12.9% of all ovarian cancers in Ontario occur in the 0.7% of women in the general population who have a lifetime ovarian cancer risk in excess of 5%, the majority of whom carry a mutation in BRCA1 or BRCA2. A model for estimating ovarian cancer risk: Application for preventive oophorectomy. Giannakeas V, et al. Gynecol Oncol. 2015. http://www.ncbi.nlm.nih.gov/m/pubmed/26341709/?from=brca1&i=2
423 The median age at RRSO was 44.5 (range 28-73) years. Of the women undergoing RRSO, 78.3 % needed ≤3 consultations to reach this decision. Multivariable analysis showed a significant difference in RRSO uptake for women with a history of RRM [OR 3.66 95 % CI (1.12-11.98)], but no significant difference in women with a history of breast cancer [OR 1.38 95 % CI (0.50-3.79)], nor with a family history of ovarian and/or breast cancer [OR 1.10 95 % CI (0.44-2.76)]. We conclude that RRSO counseling, without the alternative of screening, is effective. The uptake is increased in women with a history of RRM. Fam Cancer. 2015 Aug 12. [Epub ahead of print] The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy. van der Aa JE1, Hoogendam JP, Butter ES, Ausems MG, Verheijen RH, Zweemer RP. http://www.ncbi.nlm.nih.gov/pubmed/26264902
424 Increased calcium intake, whether from dietary sources or supplements, is unlikely to have a substantive clinical effect on bone mineral density (BMD) or fracture risk, two analyses in the BMJ find. Researchers, using data from randomized or cohort studies, examined whether calcium increased BMD or lowered fracture risk in people over age 50. BMD, in trials comprising nearly 14,000 participants, showed small increases (1%–2%) with dietary calcium or supplements. The authors observe that such increases are "unlikely to translate into clinically meaningful reductions in fractures." Similarly, fracture risk was not reduced with increased dietary calcium. Supplements initially showed a beneficial effect, which disappeared when the analysis was confined to trials at lowest risk for bias; those trials included some 45,000 people. An editorialist finds "puzzling" the recommendations from various organizations for almost universal calcium supplementation in older adults. He writes that "it is surely time to reconsider" such an approach. New England Journal of Medicine, Medical News | Physician's First Watch September 30, 2015 Increased Calcium Intake Doesn't Reduce Fracture Risk in Older People By Joe Elia Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM http://www.jwatch.org/fw110689/2015/09/30/increased-calcium-intake-doesnt-reduce-fracture-risk?query=pfw
425 Cholesterol and neural issues - Alzheimer's Cholesterol levels linked to brain deposits that cause Alzheimer's Published: Tuesday 31 December 2013 at 8am PST Alzheimer's / Dementia Cholesterol Neurology / Neuroscience add your opinion email MNT featured Academic journal MNT Knowledge Center High good and low bad cholesterol are not just good for the heart but also the brain, suggests new research published in JAMA Neurology. http://www.medicalnewstoday.com/articles/270710.php
426 Simple ovarian cysts are common incidental findings among women over age 55 upon transvaginal ultrasonography, and remain common after several screening rounds and as women age. Simple cysts frequently resolve or persist without progression. Women with simple ovarian cysts do not appear to be at increased risk of developing invasive ovarian cancer. These findings support recent recommendations to follow unilocular simple cysts in post-menopausal women without intervention. Am J Obstet Gynecol. Author manuscript; available in PMC 2011 Apr 1. Published in final edited form as: Am J Obstet Gynecol. 2010 Apr; 202(4): 373.e1–373.e9. Published online 2010 Jan 22. doi: 10.1016/j.ajog.2009.11.029 PMCID: PMC2847634 NIHMSID: NIHMS172433 Prevalence, incidence and natural history of simple ovarian cysts among women over age 55 in a large cancer screening trial Robert T. Greenlee, Ph.D., M.P.H.,* Bruce Kessel, M.D., Craig R. Williams, B.S., Thomas L. Riley, B.S., Lawrence R. Ragard, M.D., Patricia Hartge, Sc.D., Saundra S. Buys, M.D., Edward E. Partridge, M.D., and Douglas J. Reding, M.D., M.P.H. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847634/
427 OBJECTIVE: We assessed whether asymptomatic ovarian abnormalities detected on ultrasonography in postmenopausal women are precursors to ovarian cancer.

STUDY DESIGN: We compared the transvaginal ultrasonographic findings from the initial examination of 20,000 postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening with data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suggestive characteristic(s) of a septum, a solid component, or an irregular or thick wall ("complex cysts") from simple sonolucent cysts with none of those features.

RESULTS: High parity, a strong ovarian cancer protective factor, was negatively associated with complex cysts (odds ratio for > or =5 births vs no births, 0.72; 95% confidence interval, 0.53-0.97), but long-term oral contraceptive use, another strong ovarian cancer protective factor, was not associated with complex cysts (odds ratio, 0.96; 95% confidence interval, 0.76-1.20). A family history of ovarian cancer or multiple breast cancers, a strong risk factor for cancer, was not associated with complex cysts (odds ratio, 0.99; 95% confidence interval, 0.68-1.44). Other abnormalities found on ultrasonography (including simple cysts, bilateral cysts, or all abnormalities combined) also did not share the established risk factors for ovarian malignancy. We did not identify any combination of features of abnormalities (septum, echogenicity, size, or papillary projections) that manifested the cancer risk factor profile.

CONCLUSIONS: Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasonography are determined to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer. The eventual identification of such precursors will yield opportunities for earlier diagnosis, screening of high-risk groups, and better understanding of the cause of this often lethal malignancy.
Am J Obstet Gynecol. 2000 Nov;183(5):1232-7. Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors: preliminary data from the prostate, lung, colon, and ovarian cancer screening trial. Hartge P1, Hayes R, Reding D, Sherman ME, Prorok P, Schiffman M, Buys S. http://www.ncbi.nlm.nih.gov/pubmed/11084571
428 OBJECTIVE: The aim of this study was to determine the risk of malignancy in cystic ovarian tumors < 10 cm in diameter in asymptomatic postmenopausal women or women >or =50 years of age.

METHODS: All cystic ovarian tumors detected by transvaginal sonography screening in asymptomatic postmenopausal women or women > or =50 years of age were evaluated with respect to size and morphology. Histology was recorded on all tumors removed surgically. Follow-up data were available both on patients undergoing surgery and on those who elected to be followed without operative intervention.

RESULTS: Unilocular cystic tumors were detected in 256 of 7705 patients (3.3%). All tumors were < 10 cm in diameter and 90% were < 5 cm in diameter. One hundred twenty-five of these cysts (49%) resolved spontaneously within 60 days and 131 (51%) persisted.

Forty-five patients with persisting ovarian cysts underwent operative removal of these tumors. Thirty-two patients had ovarian serous cystadenomas (benign ovarian epithelial tumors), and the remainder had a variety of benign lesions. There were no cases of ovarian carcinoma in this group.

Eighty-six patients with unilocular cystic ovarian tumors were followed at 3- to 6-month intervals without surgery, and none have developed ovarian cancer.

Complex cystic ovarian tumors were detected in 250 patients (3.2%). All tumors were < 10 cm in diameter and 89% were < 5 cm in diameter. One hundred thirty-five (55%) resolved spontaneously within 60 days, and 115 (45%) persisted. One hundred fourteen of these patients underwent operative tumor removal. Seven patients had ovarian carcinoma, 1 had primary peritoneal cancer, and 1 had metastatic breast cancer to the ovary.

CONCLUSION: Unilocular ovarian cysts < 10 cm in diameter in asymptomatic postmenopausal women or women > or =50 years of age are associated with minimal risk for ovarian cancer. In contrast, complex ovarian cysts with wall abnormalities or solid areas are associated with a significant risk for malignancy. These data are important in determining optimal strategies for operative intervention in these patients. (DM NOTE: 1/10 of 1% had cancer from original 7,705 group. 1.7% of all women with cyst had cancer. 3.6% of complex cysts had cancer.)
Gynecol Oncol. 1998 Apr;69(1):3-7. The malignant potential of small cystic ovarian tumors in women over 50 years of age. Bailey CL1, Ueland FR, Land GL, DePriest PD, Gallion HH, Kryscio RJ, van Nagell JR Jr. http://www.ncbi.nlm.nih.gov/pubmed/9570990
429 OBJECTIVE: To determine the natural history and to estimate the risk of malignancy of unilocular ovarian cystic tumors less than 10 cm in diameter followed conservatively by transvaginal ultrasound.

METHODS: From 1987 to 2002, 15,106 asymptomatic women at least 50 years old entered the University of Kentucky's Ovarian Cancer Screening Program and underwent initial transvaginal ultrasonography. If the screen revealed nothing abnormal, women were asked to repeat transvaginal ultrasonography yearly. If the screen revealed abnormalities, transvaginal ultrasonography was repeated in 4 to 6 weeks, along with Doppler flow ultrasonography and CA 125 testing.

RESULTS: Of the 15,106 women at least 50 years old, 2763 women (18%) were diagnosed with 3259 unilocular ovarian cysts. A total of 2261 (69.4%) of these cysts resolved spontaneously, 537 (16.5%) developed a septum, 189 (5.8%) developed a solid area, and 220 (6.8%) persisted as a unilocular lesion. During this time, 27 women received a diagnosis of ovarian cancer, and ten had been previously diagnosed with simple ovarian cysts. All ten of these women, however, developed another morphologic abnormality, experienced resolution of the cyst before developing cancer, or developed cancer in the contralateral ovary. No woman with an isolated unilocular cystic ovarian tumor has developed ovarian cancer in this population.

CONCLUSION: The risk of malignancy in unilocular ovarian cystic tumors less than 10 cm in diameter in women 50 years old or older is extremely low. The majority will resolve spontaneously and can be followed conservatively with serial transvaginal ultrasonography.
Obstet Gynecol. 2003 Sep;102(3):594-9. Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter. Modesitt SC1, Pavlik EJ, Ueland FR, DePriest PD, Kryscio RJ, van Nagell JR Jr. http://www.ncbi.nlm.nih.gov/pubmed/12962948
430 Abstract: The postmenopausal ovary continues to produce cysts; the prevalence in an ovarian cancer screening population approaches 18%. Yet 60% to 70% of unilocular cysts resolve spontaneously. Optimal management of an asymptomatic adnexal mass allows surveillance of women at low malignancy risk while triaging intermediate/high-risk women to surgery. Women with unilocular cysts on transvaginal ultrasound (TVS) and a normal CA-125 are monitored with repeat TVS at 3 to 6 months. Those with a complex mass <5 cm and normal CA-125 should have repeat TVS and CA-125 testing in 4 weeks. Surgery is recommended for any women with increasing morphologic complexity or a rising CA-125. Clin Obstet Gynecol. 2006 Sep;49(3):506-16. The incidental postmenopausal adnexal mass. McDonald JM1, Modesitt SC. http://www.ncbi.nlm.nih.gov/pubmed/16885657
431

My comments: Essentially, there is no longer any reason to see an OB/GYN unless you are pregnant. If the only thing an OB/GYN is now doing at other times is looking for doemstic violence or vulvar lesions, these can easily be accomplished with the patient's GP, who isn't incented by surgery quotas to "find something."

"In developing recommendations for the components of the well-woman visit, task force members focused on what should be done to optimize health for the average women. The task force did not examine data supporting the concept of an annual visit but accepted that the annual visit is an essential part of preventive health care."

Decade of Data on Denosumab for Osteoporosis Reassuring FRAX Misses Fracture Risk With Mental Illness, Related Meds Emperor's Mukherjee on the Three Laws of Medicine Gestational Diabetes: Ultrasounds Overestimate LGA Risk Medscape Medical News ACOG Releases New Guidance for Well-Woman Visit Janis C. Kelly September 11, 2015 http://www.medscape.com/viewarticle/850856
432 LDL cholesterol rises significantly in 31 premenopausal women who'd had a bilateral oophorectomy ( 3.57 (SD 0.66) mmol/l to 4.21 (SD 0.84) mmol/l within 6 weeks after operation) Br J Obstet Gynaecol. 1990 Jan;97(1):78-82. Effects of bilateral oophorectomy on lipoprotein metabolism. Farish E1, Fletcher CD, Hart DM, Smith ML. http://www.ncbi.nlm.nih.gov/pubmed/2306431
433 Diabetes mellitus risk higher in women with BSO Physiol Res. 2014;63 Suppl 3:S395-402. Bilateral oophorectomy may have an unfavorable effect on glucose metabolism compared with natural menopause. Lejsková M1, Piťha J, Adámková S, Auzký O, Adámek T, Babková E, Lánská V, Alušík Š. http://www.ncbi.nlm.nih.gov/pubmed/25428745
434 Higher risk of metabolic syndrome in BSO women over 24 years in Norway Int J Gynecol Cancer. 2009 May;19(4):634-40. doi: 10.1111/IGC.0b013e3181a13058. Prevalence and determinants of metabolic syndrome and elevated Framingham risk score in epithelial ovarian cancer survivors: a controlled observational study. Liavaag AH1, Tonstad S, Pripp AH, Tropé C, Dørum A. http://www.ncbi.nlm.nih.gov/pubmed/19509562
435 Results: The mean age of the patients was 48.6±2.9 years. The mean 2-h glucose level in OGTT changed from 26.7 before surgery to 111.1 µUnit/ml (P=0.030). The mean level of lipid profile before and after surgery for TG was 132.3 versus 181.2 mg/dl (P=0.005), total cholesterol 177.4 versus 206.7 mg/dl (P=0.0001) and LDL 98.4 versus 115.3 mg/dl (P=0.003). The other variables showed no significant difference. Conclusion: The results indicate that lipid profile changes like increase of TG, total cholesterol and LDL should be considered before removing the ovary during hysterectomy in premenopausal women. Caspian J Intern Med. 2014 Spring; 5(2): 114–117. PMCID: PMC3992239 Glucose Tolerance and lipid profile changes after surgical menopause Shahla Yazdani, MD,1,2 Majid Sharbatdaran, MD,3 Mohammad Abedi Samakoosh, MD,4 Zinatossadat Bouzari, MD,*,1,5 and Zahra Masoudi, MD6 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992239/
436 RESULTS: TC level was significantly higher in the OPX group than in the premenopausal control group, being 8995 +/- 244 (mean +/- S.E.) mmol/l and 7757 +/- 228 mmol/l, respectively. LDL-C and Apo-B levels and the index of arteriosclerosis were all significantly higher in the OPX group than in the premenopausal control groups. However, there were no significant intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a). CONCLUSIONS: The above results demonstrated that, in spite of no reduction in HDL-C, the blood levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX induces cardiovascular diseases and, therefore, follow-up of the changes in lipid metabolism is required, paying special attention to Apo-B and LDL-C. Maturitas. 1998 Jun 3;29(2):147-54. Influence of bilateral oophorectomy upon lipid metabolism. Suda Y1, Ohta H, Makita K, Takamatsu K, Horiguchi F, Nozawa S. http://www.ncbi.nlm.nih.gov/pubmed/9651904
437 HCUP inpatient hysterectomy and oophorectomy stats, 5th and 6th most common procedures of any kind for women in 2006   https://www.hcup-us.ahrq.gov/reports/factsandfigures/facts_figures_2006.jsp
438 Niemann Pick C (NPC), a fatal autosomal-recessive neurovisceral lipid storage disorder, is a juvenile dementia with massive nerve-cell loss and cytoskeletal abnormalities in cerebral neurons. These abnormalities consist of tangles of tau protein, which is otherwise highly soluble and usually stabilizes the microtubules. Immunologically and ultrastructurally similar tangles are seen some decades later in patients with Alzheimer's disease (AD). There is evidence that tangle-bearing cells in both diseases show higher levels of free (i. e. filipin-positive) cholesterol than adjacent tangle-free nerve cells. The cholesterol accumulates either in a more diffuse way (mainly in AD) or in granule-like accumulations (mainly in NPC). In NPC, neuron cholesterol may originate from sources other than the alimentary tract. Experiments with a NPC mouse model revealed that even in pure neuron cultures, the NPC -/- neurons accumulate free cholesterol in contrast to NPC-wt littermates, suggesting that the cholesterol is either synthesized by the neurons or liberated from degenerated ones before being taken up by the endosomal/lysosomal pathway. The accumulation of free cholesterol in the somata of NPC neurons is associated with a decrease of cholesterol levels in myelin sheaths. In terms of tau protein, NPC -/- mice exhibit higher levels of AT8-positive tau, suggesting that the phosphorylation-dependent mAb AT8 has detected a tau-epitope in a state considered to represent early stages of tangle formation. Concomitantly to the increase in free intracellular cholesterol, the rate-limiting enzyme in cholesterol and isoprenoid biosynthesis, HMG-CoA reductase, was found to be significantly reduced. Experimental blockade of the enzyme's activity by application of the lipid-lowering drug lovastatin showed subcellular shifts in tau phosphorylation as monitored with mAbs AT8, 12E8 and others. In summary, the data showed interesting similarities between NPC and AD suggesting some pathological metabolic pathway in common. Cholesterol and tau protein--findings in Alzheimer's and Niemann Pick C's disease. (PMID:14574625) Abstract Citations BioEntities Related Articles External Links Ohm TG, Treiber-Held S, Distl R, Glöckner F, Schönheit B, Tamanai M, Meske V Institute of Anatomy, Department of Clinical Cell- and Neurobiology, Charité, Humboldt University, Berlin, Germany. thomas_georg.ohm@charite.de Pharmacopsychiatry [2003, 36 Suppl 2:S120-6] http://europepmc.org/abstract/MED/14574625
439 Abnormal hyperphosphorylation and aggregation of microtubule-associated protein tau play a crucial role in neurodegeneration of Alzheimer’s disease (AD). Anesthesia has been associated with cognitive impairment and the risk for AD. Here we investigated the effects of anesthesia on site-specific tau phosphorylation and the possible mechanisms. We found that anesthesia for short periods (30 sec to 5 min) induced tau phosphorylation at Thr181, Ser199, Thr205, Thr212, Ser262, and Ser404 to small, but significant, extents, which appeared to result from anesthesia-induced activation of stress-activated protein kinases. Anesthesia for a longer time (1 h) induced much more dramatic phosphorylation of tau at the above sites, and the further phosphorylation may be associated with hypothermia induced by anesthesia. Anesthesia-induced tau phosphorylation appears to be specific because the increased phosphorylation was only seen at half of the tau phosphorylation sites studied and was not observed in global brain proteins. These studies clarified the dynamic changes of tau phosphorylation at various sites and, thus, served as a fundamental guide for future studies on tau phosphorylation by using brains of anesthetized experimental animals. Our findings also provide a possible mechanism by which anesthesia may cause postoperative cognitive impairment and increase the risk for AD. J Alzheimers Dis. Author manuscript; available in PMC 2010 Feb 26. Published in final edited form as: J Alzheimers Dis. 2009 Mar; 16(3): 619–626. doi: 10.3233/JAD-2009-1003 PMCID: PMC2829310 NIHMSID: NIHMS179256 Anesthesia Induces Phosphorylation of Tau Xiaoqin Run,a,b,1 Zhihou Liang,a,c,1 Lan Zhang,d Khalid Iqbal,a Inge Grundke-Iqbal,a and Cheng-Xin Gonga,* http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829310/
440

The impact of fibroids on women's lives and what they are looking for in terms of solution.

Women waited an average of 3.6 years before seeking treatment for leiomyomas, and 41% saw ≥2 health care providers for diagnosis. Almost a third of employed respondents (28%) reported missing work due to leiomyoma symptoms, and 24% believed that their symptoms prevented them from reaching their career potential. Women expressed desire for treatments that do not involve invasive surgery (79%), preserve the uterus (51%), and preserve fertility (43% of women aged <40 years).

Am J Obstet Gynecol. 2013 Oct;209(4):319.e1-319.e20. doi: 10.1016/j.ajog.2013.07.017. Epub 2013 Jul 24. The impact of uterine leiomyomas: a national survey of affected women. Borah BJ1, Nicholson WK, Bradley L, Stewart EA. http://www.ncbi.nlm.nih.gov/pubmed/23891629
441 Data for UAE supports it as the best alt treatment to hysterectomy for adenomyosis. Geburtshilfe Frauenheilkd. 2013 Sep;73(9):924-931. Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy. Taran FA1, Stewart EA2, Brucker S1. http://www.ncbi.nlm.nih.gov/pubmed/24771944
442 Comparing cost-effectivess of three fibroid treatment alternatives: Myomectomy, MRgFUS, and UAE were similarly effective in terms of QALYs gained. Depending on assumptions about costs and willingness to pay for additional QALYs, all three treatments can be deemed cost effective in a 5-year time frame. J Comp Eff Res. 2014 Sep;3(5):503-14. doi: 10.2217/cer.14.32. Epub 2014 May 30. Cost-effectiveness of uterine-preserving procedures for the treatment of uterine fibroid symptoms in the USA. Cain-Nielsen AH1, Moriarty JP, Stewart EA, Borah BJ. http://www.ncbi.nlm.nih.gov/pubmed/24878319
443 Combined results from the Mayo Clinic Cohort Study of Oophorectomy and Aging and from a Danish nationwide cohort study: Compared with women with no gynecologic surgeries, the risk of cognitive impairment or dementia was increased in women who had hysterectomy alone, further increased in women who had hysterectomy with unilateral oophorectomy, and further increased in women who had hysterectomy with bilateral oophorectomy. The risk increased with younger age at the time of the surgery. Neurodegener Dis. 2012;10(1-4):175-8. doi: 10.1159/000334764. Epub 2012 Jan 21. Hysterectomy, oophorectomy, estrogen, and the risk of dementia. Rocca WA1, Grossardt BR, Shuster LT, Stewart EA. http://www.ncbi.nlm.nih.gov/pubmed/22269187
444 Hysterectomy has risk factors of its own assoc with incr in obesity which incr cardiovascular disease risk Menopause. 2015 Jul 13. [Epub ahead of print] Cardiovascular risk factors and diseases in women undergoing hysterectomy with ovarian conservation. Laughlin-Tommaso SK1, Khan Z, Weaver AL, Schleck CD, Rocca WA, Stewart EA. http://www.ncbi.nlm.nih.gov/pubmed/26173076
445 OBJECTIVE: To review the data on long-term outcomes in women who underwent prophylactic bilateral oophorectomy, a common surgical procedure that has more than doubled in frequency since the 1960s. STUDY DESIGN: Literature review of the published data on the consequences of prophylactic bilateral oophorectomy. Special emphasis was given to the Mayo Clinic Cohort Study of Oophorectomy and Aging. Main outcome measures Overall mortality, cardiovascular disease, cognitive impairment and dementia, parkinsonism, osteoporosis, psychological wellbeing and sexual function. RESULTS: There is a growing body of evidence suggesting that the premature loss of ovarian function caused by bilateral oophorectomy performed before natural menopause is associated with several negative outcomes. In particular, studies have revealed an increased risk of premature death, cardiovascular disease, cognitive impairment or dementia, parkinsonism, osteoporosis and bone fractures, decline in psychological wellbeing and decline in sexual function. The effects involve different organs (e.g. heart, bone, or brain), and different functions within organs (e.g. cognitive, motor, or emotional brain functions). Estrogen treatment may prevent some but not all of these negative outcomes. CONCLUSION: The potential adverse effects of prophylactic bilateral oophorectomy on heart health, neurological health, bone health and quality of life should be carefully weighed against its potential benefits for cancer risk reduction in women at average risk of ovarian cancer. Menopause Int. 2008 Sep;14(3):111-6. doi: 10.1258/mi.2008.008016. Prophylactic oophorectomy in premenopausal women and long-term health. Shuster LT1, Gostout BS, Grossardt BR, Rocca WA. http://www.ncbi.nlm.nih.gov/pubmed/18714076
446 OBJECTIVE: To understand the neuropsychological basis of dementia risk among persons in the spectrum including cognitive normality and mild cognitive impairment. METHODS: We quantitated risk of progression to dementia in elderly persons without dementia from 2 population-based studies, the Framingham Heart Study (FHS) and Mayo Clinic Study of Aging (MCSA), aged 70 to 89 years at enrollment. Baseline cognitive status was defined by performance in 4 domains derived from batteries of neuropsychological tests (that were similar but not identical for FHS and MCSA) at cut scores corresponding to SDs of ≤-0.5, -1, -1.5, and -2 from normative means. Participants were characterized as having no cognitive impairment (reference group), or single or multiple amnestic or nonamnestic profiles at each cut score. Incident dementia over the following 6 years was determined by consensus committee at each study separately. RESULTS: The pattern of hazard ratios for incident dementia, rates of incident dementia and positive predictive values across cognitive test cut scores, and number of affected domains was similar although not identical across the FHS and MCSA. Dementia risks were higher for amnestic profiles than for nonamnestic profiles, and for multidomain compared with single-domain profiles. CONCLUSIONS: Cognitive domain subtypes, defined by neuropsychologically derived cut scores and number of low-performing domains, differ substantially in prognosis in a conceptually logical manner that was consistent between FHS and MCSA. Neuropsychological characterization of elderly persons without dementia provides valuable information about prognosis. The heterogeneity of risk of dementia cannot be captured concisely with one test or a single definition or cutpoint. Neurology. 2015 Nov 10;85(19):1712-21. doi: 10.1212/WNL.0000000000002100. Epub 2015 Oct 9. Spectrum of cognition short of dementia: Framingham Heart Study and Mayo Clinic Study of Aging. Knopman DS1, Beiser A2, Machulda MM2, Fields J2, Roberts RO2, Pankratz VS2, Aakre J2, Cha RH2, Rocca WA2, Mielke MM2, Boeve BF2, Devine S2, Ivnik RJ2, Au R2, Auerbach S2, Wolf PA2, Seshadri S2, Petersen RC2. http://www.ncbi.nlm.nih.gov/pubmed/26453643
447 Analysis of increased use by gender in US of anti-depressants Arch Womens Ment Health. 2014 Dec;17(6):485-92. doi: 10.1007/s00737-014-0450-7. Epub 2014 Aug 13. Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population. Zhong W1, Kremers HM, Yawn BP, Bobo WV, St Sauver JL, Ebbert JO, Finney Rutten LJ, Jacobson DJ, Brue SM, Rocca WA. http://www.ncbi.nlm.nih.gov/pubmed/25113318
448 Three risk factors by gender for dementia - oophorectomy is one of the three Maturitas. 2014 Oct;79(2):196-201. doi: 10.1016/j.maturitas.2014.05.008. Epub 2014 May 27. Sex and gender differences in the causes of dementia: a narrative review. Rocca WA1, Mielke MM2, Vemuri P3, Miller VM4. http://www.ncbi.nlm.nih.gov/pubmed/24954700
449 Three Alzheimer's Disease sub-types: . Inflammatory - activin, neuro-plasticity; non-inflammatory - insulin resistance, hormonal loss oophorectomy; cortical atrophy
Metabolic profiling distinguishes three subtypes of Alzheimer's disease Dale E. Bredesen1, 2 1 Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California, Los Angeles, CA 90095, USA; 2 Buck Institute for Research on Aging, Novato, CA 94945, USA http://www.impactaging.com/papers/v7/n8/full/100801.html
450 Proteinopathies and Parkinson's - gender analysis - activin JAMA Neurol. 2013 Jul;70(7):859-66. doi: 10.1001/jamaneurol.2013.114. Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism. Savica R1, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA. http://www.ncbi.nlm.nih.gov/pubmed/23689920
451

Most women experience menopause between the ages of 45 and 55 years. However, 5% of women will go through menopause early, between the ages of 40 and 45 years, and 1% of women become menopausal prematurely, before the age of 40 years [1]. The causes of premature or early menopause are multiple and range from the most common, bilateral oophorectomy, to more rare causes such as genetic, autoimmune, or infectious etiologies. There are multiple adverse long-term health consequences associated with premature or early menopause, including increased risk of dementia, parkinsonism, glaucoma, depression, anxiety, osteoporosis, coronary heart disease, heart failure, sexual dysfunction, and early death. Replacing estrogen mitigates some of these risks, although it may not completely protect against the increased risk of parkinsonism, glaucoma, mood disorders, and sexual dysfunction.

The ovaries are both reproductive and endocrine organs. They secrete hormones both before menopause (primarily estrogen, progesterone, and testosterone) and after (primarily testosterone, androstenedione, and dehydroepiandrosterone). Ovarian hormones have important reproductive actions; however, they also have important endocrine actions mediated by receptors spread throughout most tissues and organs of the body.

Removal of the ovaries reduces the risk of ovarian (by 80–90%) and breast (by 50–60%) cancer; however, it increases the risk of all-cause mortality (28%), lung cancer (45%), coronary heart disease (33%), stroke (62%), cognitive impairment (60%), parkinsonism (80%), psychiatric symptoms (50–130%), osteoporosis and bone fractures (50%), and impaired sexual function (40–110%). The magnitude of the risk varies depending on the study referenced, the age at the time of oophorectomy, and the use of estrogen therapy after the surgery [2]. With regard to bilateral oophorectomy prior to the natural age of menopause, medical practice should follow the principle of 'primum non nocere' (first do no harm). Bilateral oophorectomy performed electively at the time of hysterectomy for a benign indication is now under scrutiny and critical reappraisal because the long-term risks may outweigh the benefits in the majority of women [2]. The scientific debate about the risks and benefits of prophylactic bilateral oophorectomy continues, and many women continue to undergo prophylactic oophorectomy in 2015 [3-5].

We suggest that the evidence is sufficient to change this practice. At the time of hysterectomy for a benign condition, if the ovaries are normal and the woman does not carry a high-risk genetic variant (e.g. BRCA1 or BRCA2 mutation) or does not have a strong family history of ovarian cancer, the ovaries should be conserved. This conservative practice is particularly important in younger women [2,4]. The concept of hormone replacement therapy should be re-introduced in clinical practice. Women who experience premature or early menopause, regardless of cause, are exposed to risk from abnormal estrogen deprivation. The guideline-based recommendation to use the lowest possible dose of estrogen therapy for the shortest amount of time needed to control menopausal symptoms is not appropriate for these women. Instead, rather than aiming only for symptom relief, there is a need to replace the lost endocrine function of the ovary, much as thyroid hormone is administered following thyroidectomy. Higher doses of estradiol may be needed to approximate premenopausal serum estradiol levels. For example, estrogen-containing hormonal contraception (which provides much higher doses of estrogen than menopausal hormone therapy) is used in women with primary ovarian insufficiency (POI) to provide both hormone replacement and contraception.

Although monitoring serum estradiol levels is not recommended as part of current estrogen therapy guidelines, this recommendation should be reconsidered for women given estrogen replacement for premature or early menopause. Although there is a lack of data on the precise range of estradiol levels (serum or tissue) necessary to protect the brain and heart, there is evidence for the range associated with bone preservation [6,7]. Monitoring serum estradiol levels was not useful with conjugated equine estrogens which contain numerous estrogenic components other than estradiol, but could be useful with the formulations of estradiol used more commonly now. Consider the case of a young oophorectomized woman who continues to have bothersome vasomotor symptoms and sexual dysfunction despite a dose of 100 μg of transdermal estradiol. Is she adequately absorbing the estradiol? Is the dose simply too low? Or, is the estradiol level in a premenopausal range but she is androgen deficient? These are important clinical questions that have not been addressed in clinical trials. In addition to losing estrogen, women who undergo bilateral salpingo-oophorectomy before the natural age of menopause also lose about 50% of their androgen production [8,9].

Although testosterone therapy is not currently routinely recommended for women who have had early oophorectomy or POI [10], sexual dysfunction in women with early menopause is common, and evidence suggests that replacing testosterone in oophorectomized women with sexual dysfunction may be beneficial [11,12]. However, the long-term safety and efficacy of testosterone therapy in women have not been established, and standardized testosterone preparations are not readily available for women in most countries.

If there is a clear indication for bilateral oophorectomy in a premenopausal woman, or if a woman has experienced POI, several key concepts should be considered: 1. The results of the Women’s Health Initiative trials do not apply directly to women who have experienced premature or early menopause. 2. Most women who undergo bilateral oophorectomy or POI prior to age 45, and who do not have a history of a hormone-sensitive cancer or another specific contraindication, will benefit from hormone therapy not only for vasomotor symptom management but also for the prevention of adverse cardiovascular, bone, and neuro-cognitive effects related to premature estrogen deficiency (estrogen replacement therapy). 3. Several medical societies recommend continuing estrogen therapy at least until the age of natural menopause in women with premature or early menopause [1]. 4. Although data are lacking, higher doses of estrogen (at least the equivalent of 100 μg of transdermal estradiol) may be needed to approximate blood estradiol concentrations similar to those of menstruating women. 5. Women with premature or early menopause who experience sexual dysfunction may benefit from testosterone therapy, although questions remain regarding long-term safety and efficacy of this treatment. In summary, women who undergo bilateral oophorectomy or experience POI before the average age of menopause should receive adequate hormonal treatment [1]. Stephanie S. FaubionWomen's Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA and Carol L. KuhleWomens Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA and Lynne T. ShusterWomens Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA and Walter A. RoccaDivision of Epidemiology, Department of Health Sciences Research, and Department of Neurology, Mayo Clinic, Rochester, MN, USA References 1. Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015;18:483-91 http://www.ncbi.nlm.nih.gov/pubmed/25845383 2. Rocca WA, Ulrich LG. Oophorectomy for whom and at what age? Primum non nocere. Maturitas 2012;71:1-2 http://www.ncbi.nlm.nih.gov/pubmed/22079872 3. Llaneza P, Pérez-López FR. Rethinking elective bilateral oophorectomy at the time of hysterectomy for benign disease. Maturitas 2013;76:109-10 http://www.ncbi.nlm.nih.gov/pubmed/23849176 4. Harmanli O. Save the ovaries in reproductive years… and maybe the uterus, too?Menopause 2014;21:561-2 http://www.ncbi.nlm.nih.gov/pubmed/24755899 5. Harmanli O, Shinnick J, Jones K, St Marie P. Obstetrician-gynecologists opinions on elective bilateral oophorectomy at the time of hysterectomy in the United States: a nationwide survey. Menopause 2014;21:35560 http://www.ncbi.nlm.nih.gov/pubmed/23942250 6. Rogers A, Saleh G, Hannon RA, Greenfield D, Eastell R. Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 2002;87:4470-5 http://www.ncbi.nlm.nih.gov/pubmed/12364420 7. Ettinger B, Pressman A, Sklarin P, Bauer DC, Cauley JA, Cummings SR. Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures. J Clin Endocrinol Metab 1998;83:2239-43 http://www.ncbi.nlm.nih.gov/pubmed/9661589 8. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90:3847-53 http://www.ncbi.nlm.nih.gov/pubmed/15827095 9. Shifren JL. Androgen deficiency in the oophorectomized woman. Fertil Steril 2002;77(Suppl 4):S60-2 http://www.ncbi.nlm.nih.gov/pubmed/12007904 10. Wierman ME, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2014;99:3489510 http://www.ncbi.nlm.nih.gov/pubmed/25279570 11. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000;343:682-8 http://www.ncbi.nlm.nih.gov/pubmed/10974131 12. Buster JE, Kingsberg SA, Aguirre O, et al. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Obstet Gynecol 2005;105:94452 http://www.ncbi.nlm.nih.gov/pubmed/15863529 Scientific Editor: Amos Pines (apines@netvision.net.il) Editorial Consultant: Jean Wright (jwright.ims@btopenworld.com)

International Menopause Society, Date of release: 20 July, 2015 Adverse long-term health outcomes associated with premature or early menopause

Stephanie S. FaubionWomen's Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA

and

Carol L. KuhleWomens Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA

and

Lynne T. ShusterWomens Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA

and

Walter A. RoccaDivision of Epidemiology, Department of Health Sciences Research, and Department of Neurology, Mayo Clinic, Rochester, MN, USA

http://www.imsociety.org/manage/updates_export_press.php?menopauseliveID=2755
452 Roles of dopamine and norepinephrine in Parkinson's - also Lewy bodies NIH Senior Health - Parkinson's Disease: What Causes Parkinson's Disease? http://nihseniorhealth.gov/parkinsonsdisease/whatcausesparkinsonsdisease/01.html
453 The ovaries and fallopian tubes contain stem cells. (DM note: Is this why doctors refuse to stop removing healthy organs?)

Reprod Sci. Author manuscript; available in PMC 2011 Jul 4. Published in final edited form as: Reprod Sci. 2009 Feb; 16(2): 126–139. doi: 10.1177/1933719108329956 PMCID: PMC3129037 NIHMSID: NIHMS293620 Stem Cells and Female Reproduction Hongling Du, MD, PhD and Hugh S. Taylor, MD

and

BioMed Central, news release, June 18, 2009

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129037/

and

http://consumer.healthday.com/women-s-health-information-34/hysterectomy-news-399/hysterectomies-could-be-source-of-stem-cells-628138.html

454

Women produce 15 to 20 mature eggs each month

A woman in NY, the only state where selling eggs is legal, can get paid $8K a month

BabyCentre and NY center for repro

http://www.babycentre.co.uk/ovulation

and

https://www.centerforhumanreprod.com/egg-donation/donors/

455 Adult stem cells have been identified in diverse tissues, including human bone marrow, breast, prostate, brain and liver. We hypothesised that adult stem cells reside in the endometrium, a highly proliferative, cyclically regenerating tissue. Our research has demonstrated, for the first time, that human endometrium contains a small population of epithelial cells (0.22%) and stromal cells (1.25%) that exhibit stem/progenitor cell behaviour in vitro; clonogenicity. The progeny in these colonies have been characterised and growth factors supporting clonogenicity identified. The goal is to examine the role of putative endometrial stem/progenitor cells in proliferative disorders of human endometrium, such as endometriosis, adenomyosis, endometrial hyperplasia and endometrial cancer, and the action of hormone-replacement therapy on the post-menopausal endometrium. Aust N Z J Obstet Gynaecol. 2004 Oct;44(5):380-6. Stem cells in gynaecology. Gargett CE1. http://www.ncbi.nlm.nih.gov/pubmed/15387855
456

Fallopian tubes as a source of stem cells.

Abstract Background: The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbili cal cords, dental pulp and adipos e tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and as sess the differentiation potential of MSCs from human fallopian tubes (hFTs). Methods: Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent in vitro adipogenic, chondrogenic, osteogenic, and myogenic differentiation. Results: Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as human tube MSCs (htMSCs). Conclusion: Human tube MSCs can be easily isolated, expanded in vitro , present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone in vitro . Background Adult mesenchymal stem cells (MSCs) are typically defined as undifferentiated multipotent cells endowed with the capacity for self-renewal and the potential to dif- ferentiate into several distinct cell lineages [1]. These progenitor cells which constitute a reservoir found within the connective tissue of most organs are involved in the maintenance and repair of tissues throughout the postnatal life of an individual.

Bio Med Central Journal of Translational Medicine Open Access Research Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discar ded in surgical procedures Tatiana Jazedje 1 , Paulo M Perin 2 , Carlos E Czeresnia 3 , Mariangela Maluf 2 , Silvio Halpern 2 , Mariane Secco 1 , Daniela F Bueno 1 , Natassia M Vieira 1 , Eder Zucconi 1 and Mayana Zatz* 1 Address: 1 Human Genome Research Center, Bios ciences Institute, University of São Paulo, Brazil Rua do Matã o, n° 106, Cidade Universitária São Paulo SP, CEP: 05508-090, Brazil, 2 CEERH Specialized Center for Human Reproduction, São Paulo, Brazil Rua Mato Grosso, n° 306 19° andar, Higienópolis São Paulo SP , CEP: 01239-040, Brazil and 3 Celula Mater, São Paulo, Braz il Al. Gabriel Monteiro da Si lva, n° 802 São Paulo SP, CEP: 01442-000, Brazil Email: Tatiana Jazedje - tatiana@ib.usp.br; Paulo M Perin - paul o@ceerh.com.br; Carlos E Czeresnia - cec@celulamater.com.br; Mariangela Maluf - mariangela@ceerh.com.br; Silvio Halpern - halpern@osite.com.br; Mariane Secco - marianesecco@usp.br; Daniela F Bueno - dbueno@usp.br; Natassia M Vieira - natassia@usp.br; Eder Zucconi - e zucconi@usp.br; Mayana Zatz* - mayazatz@usp.br
Published: 18 June 2009
http://www.biomedcentral.com/content/pdf/1479-5876-7-46.pdf
457 Write-up of Brazilian findings as above. 456 Healthday.com
Hysterectomies Could Be Source of Stem Cells Researchers eye tissues that are normally discarded after surgery
http://consumer.healthday.com/women-s-health-information-34/hysterectomy-news-399/hysterectomies-could-be-source-of-stem-cells-628138.html
458 Gynecological stem cells - a source and a target - presentation Implications of stem cells in Gynecology and Obstetrics 791 Emad Qasem Emad Qasem, Media Consultant at Sohag University Students' Union http://www.slideshare.net/emadqasem/implications-of-stem-cells-in-gynecology-and-obstetrics
459 While there has been progress in directing the development of embryonic stem cells and induced pluripotent stem cells toward a germ cell state, their ability to serve as a source of functional oocytes in a clinically relevant model or situation has yet to be established. Recent studies suggest that the adult mammalian ovary is not endowed with a finite number of oocytes, but instead possesses stem cells that contribute to their renewal. The ability to isolate and promote the growth and development of such ovarian germline stem cells (GSCs) would provide a novel means to treat infertility in women. Although such ovarian GSCs are well characterized in nonmammalian model organisms, the findings that support the existence of adult ovarian GSCs in mammals have been met with considerable evidence that disputes their existence. This review details the lessons provided by model organisms that successfully utilize ovarian GSCs to allow for a continual and high level of female germ cell production throughout their life, with a specific focus on the cellular mechanisms involved in GSC self-renewal and oocyte development. Such an overview of the role that oogonial stem cells play in maintaining fertility in nonmammalian species serves as a backdrop for the data generated to date that supports or disputes the existence of GSCs in mammals as well as the future of this area of research in terms of its potential for any application in reproductive medicine. Fertil Steril. 2014 Jan;101(1):20-30. doi: 10.1016/j.fertnstert.2013.11.009. Ovarian germline stem cells: an unlimited source of oocytes? Hanna CB1, Hennebold JD2. http://www.ncbi.nlm.nih.gov/pubmed/24382341
460 The researchers malignantly transformed hilum epithelial cells by shutting off tumor suppressor genes Trp53 and Rb1 and then transplanted these cells into mice. Seven of eight mice developed metastatic ovarian tumors. Trp53 and Rb1 are known to frequently mutate in human ovarian cancers. “Some broad implications are that similar epithelial transition/junction areas can be the source of stem-like cells susceptible to malignant transformation in other organs, such as the uterine cervix and the esophagus, and become the seeds of cancer there,” Enikolopov says. “Now we know what sort of cells to look for.” Scientists uncover source of ovarian stem-like cells prone to give rise to ovarian cancer Cold Spring Harbor, NY – In collaboration with colleagues at Cornell University, a team of cancer researchers at Cold Spring Harbor Laboratory (CSHL) has discovered cells with stem-cell properties in the ovary that can mutate to form tumors. Written by: Yevgeniy Grigoryev, guest science writer | Contact: tarr@cshl.edu | 516-367-8455 http://www.cshl.edu/news-and-features/scientists-uncover-the-source-of-novel-ovarian-stem-like-cells-prone-to-give-rise-to-ovarian-cancer.html
461 Human stem cells used to breathe new life into ovaries affected by cancer treatment UK Mirror - Baby hope for cancer patients as stem cells 'bring ovaries back to life' 00:00, 22 Oct 2015 By Andrew Gregory http://www.mirror.co.uk/news/technology-science/science/baby-hope-cancer-patients-stem-6679512
462 Sen Patty Murray writes letter praising ACOG on their 50th anniversary. [Congressional Record Volume 147, Number 33 (Tuesday, March 13, 2001)] [Senate] [Pages S2216-S2217] From the Congressional Record Online through the Government Publishing Office [www.gpo.gov] AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGIST: 50TH ANNIVERSARY TRIBUTE Mrs. MURRAY. Mr. President, I come to the floor today to pay tribute to the American College of Obstetricians and Gynecologists, ACOG, in celebration of their 50th Anniversary. I would also like to include the letter signed by several of my colleagues who have joined with me in offering congratulations to ACOG and to pay tribute to their efforts on behalf of women's health. With a membership of over 41,000 physicians specializing in obstetric-gynecologic are, ACOG is the nation's leading group of professionals dedicated to improving women's health care. ACOG is a private, voluntary, nonprofit organization. [[Page S2217]] Throughout its history, the purpose of ACOG has been to maintain the best standards of health care for women. Today, about 95 percent of American obstetricians and gynecologists are affiliated with ACOG. Over 35 percent of ACOG Fellows are women, and over 63 percent of Junior Fellows are women. ACOG works in four primary areas: Serving as a strong advocate for quality health care for women. Increasing awareness among its members and the public of the changing issues facing women's health care. Maintaining the highest standards of clinical practice and continuing education for its members. Promoting patient education and stimulating patient understanding of, and involvement in, medical care. ACOG's reliable and informative communication with us on Capitol Hill has been a valuable asset in guiding our policy debates. Congratulations to ACOG, and thank you for providing a welcome voice to Capitol Hill on women's health policy. I ask that a letter dated February 21, 2001, be printed in the Record. The letter follows: U.S. Senate, Washington, DC, February 21, 2001. Hon. Trent Lott, Senate Majority Leader, U.S. Senate, Washington, DC. Hon. Dennis Hastert, The Speaker, U.S. House of Representatives, Washington, DC. Dear Senator Lott/Mr. Speaker: We would like to take this opportunity to recognize the work of the American College of Obstetricians and Gynecologists (ACOG). We would also like to congratulate ACOG on their 50th Anniversary. With a membership of over 41,000 physicians specializing in obstetric-gynecologic care, ACOG is the nation's leading group of professionals dedicated to improving women's health care. ACOG is a private, voluntary, nonprofit organization. Throughout its history, the purpose of ACOG has been to maintain the best standards of health care for women. Today, about 95% of American obstetricians and gynecologists are affiliated with ACOG. Over 35% of ACOG Fellows are women, and over 63% of Junior Fellows are women. ACOG works in four primary areas: Serving as a strong advocate for quality health care for women. Increasing awareness among its members and the public of the changing issues facing women's health care. Maintaining the highest standards of clinical practice and continuing education for its members. Promoting patient education and stimulating patient understanding of, and involvement in, medical care. ACOG's reliable and informative communication with us on Capitol Hill has been a valuable asset in guiding our policy debates. Congratulations to ACOG--and thank you for providing a welcome voice to Capitol Hill on women's health policy. Sincerely, Patty Murray, Tom Harkin, Mary L. Landrieu, Louise M. Slaughter, Jim Jeffords, Jan Schakowsky, Arlen Specter, Jeff Bingaman, Kay Granger, Nita Lowey, Nancy L. Johnson, Sherrod Brown, Pete Stark, Patrick J. Kennedy, Ron Wyden, Barbara A. Mikulski, Henry A. Waxman, and James Greenwood. [Congressional Record Volume 147, Number 33 (Tuesday, March 13, 2001)] [Senate] [Pages S2216-S2217] From the Congressional Record Online through the Government Publishing Office [www.gpo.gov] http://www.gpo.gov/fdsys/pkg/CREC-2001-03-13/html/CREC-2001-03-13-pt1-PgS2216-4.htm
463 1,412 respondents from 57,000 members... 2013 Socioeconomic Survey of ACOG Fellows https://www.acog.org/-/media/Departments/Practice-Management-and-Managed-Care/2013SocioeconomicSurvey.pdf
464

Double-edged sword. ACOG legislative priorities: "Protect the Physician-Patient Relationship Oppose state and federal interference in the patient-physician relationship."

And inexplicably snuck in under Prevent Unintended Pregnancies and Reduce the Need for Abortions

"Support access to reproductive health services. Promote access to contraception, including emergency contraception. Advocate the use of medically accurate information. Enact Meaningful Medical Liability Reform ACOG supports caps on non-economic damages. We support meaningful alternative reforms, including safe harbors and expanded application of the Federal Tort Claims Act to on-call ob-gyns."

ACOG's Legislative Priorities http://www.acog.org/Advocacy/ACOG-Legislative-Priorities
465

OBGYNs can earn up to 21 of the required average 25 CME (continuing medical education) credits states require of them each year by lobbying Congress...

"Save the Date for the 2016 CLC ACOG’s 2016 Congressional Leadership Conference (CLC), our 34th, promises to be our best yet! Plan now to attend ACOG’s most popular advocacy event in Washington, DC, March 6-8, 2016. Following two days of training, you will lobby your Members of Congress during our Capitol Hill Lobby Day, a critical opportunity to advocate for your specialty and your patients. Attendees may also receive up to 21 CME credits. We hope to see you there!"

ACOG's Congressional Leadership Conference

(State requirements: http://www.cmeweb.com/gstate_requirements.php)

http://www.statelegislativeroundtable.org/clc/
466 Appendix - the appendix has a purpose--providing a safe haven for good germs so they can repopulate your gut if necessary ScienceMag Appendix Evolved More Than 30 Times Email Colin By Colin Barras 12 February 2013 4:35 pm http://news.sciencemag.org/plants-animals/2013/02/appendix-evolved-more-30-times
467 ACOG - should we rip out the appendix while we're in there too? We're not sure. Number 323, November 2005 (Reaffirmed 2014, Replaces No. 164, December 1995) Committee on Gynecologic Practice Format Elective Coincidental Appendectomy http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Elective-Coincidental-Appendectomy
468 Irony. Senator Murray Urges Support for Embryonic Stem Cell Research Jul 18 2001 Calls on Bush Administration to stand up for patients, provide federal investment (WASHINGTON, D.C.) – U.S. Senator Patty Murray (D-Wash.) today called on the Bush Administration to stand up for patients and medical researchers by providing federal support for embryonic stem cell research. For patients living with diseases such as Parkinson's, Multiple Sclerosis, Alzheimer's, and Diabetes, stem cell research holds promising potential in providing the tools by which to understand, treat, and someday cure, these devastating illnesses. Sen Murray's site http://www.murray.senate.gov/public/index.cfm/newsroom?ID=0bbbb6b4-ae43-451f-ad2f-4e6ee407eb94
469

Oophorectomy leads to loss of sexual desire in women with oophorectomy, and can be helped with testosterone supplement. It may also help with general sense of well-being, however, its cardiovascular risks haven't been well-researched.

Women who've had hysterectomy lose uterine contractions during orgasm. Scarring and nerve damage may result in lack of feeling.

Women who also have oophorectomy lose significant amoungs of testosterone and androstenedione.

Surgery for benign disorders accounts for 90% of hysts. The majority of women who reported a lack of interest or discomfort during sex before surgery reported that that was unchanged after.

Removing the cervix results in vaginal shortening, prolapse, bladder & bowel dysfunction due to loss of ganglian nerve function, and loss of sexual arousal and function due to its role in the Frankehauser uterovaginal plexus. Significant orgasm decreases happened at 1 year after hyst with removal of cervix.

 

Clinical Obstetrics & Gynecology: Evaluating Sexual Dysfunction in Women, Vol 40 No 3, September 1997, Julia Heiman, PhD and Cynthia Meston, PhD., Dept of Psychiatry, U of Washington, Seattle http://homepage.psy.utexas.edu/HomePage/group/MestonLAB/publications/evaluating.pdf
470

After their bachelors and 4-year MD, unlike other surgical specialties, OBGYNs only train for 4 years, none of which is general surgery training.

(General surgery - 5 years; orthopedics - 5 years; otolaryngology - 5 years with at least one year general surgery; neurosurgery - 7 years; plastic surgery - 3 years general surgery training folloed by 2-3 years training in plastic surgery specialty - 5-6 years; urology: 1-2 years general followed by 3-4 years urology - 4-6 years; cardiothoracic: 3 years general surgery followed by 3 years cardiothoracic surgery - 6 years)

American College of Surgeons Education: Section III: Surgical Specialties: Obstetrics and Gynecology https://www.facs.org/education/resources/residency-search/specialties/obgyn
471 Women bear a disproportional risk and burden for using any contraception apart from condoms. Men are willing and options are available, but pharma companies have shown no interest. NIH's Eunice Kennedy NIHCD, Diana Blithe, Ph.D., Program Director for the CDDB’s Male Contraceptive Development Program, https://www.nichd.nih.gov/news/resources/spotlight/Pages/062314-male-contraception.aspx
472 Dr Kate "I've taken out at least 1,300 healthy appendixes" O'Hanlan reports on incidental appendectomy at the time of hysterectomy. Researchgate: 257 Incidental Appendectomies During Total Laparoscopic Hysterectomy Katherine A O'Hanlan Katherine A O'Hanlan Deidre T Fisher Deidre T Fisher Michael S O'Holleran Michael S O'Holleran http://www.researchgate.net/publication/5613436_257_Incidental_Appendectomies_During_Total_Laparoscopic_Hysterectomy
473 Kate O'Hanlon OBGYN proudly tells doctor on researchgate forum that she offers an incidental appendectomy to every patient she operates on, and that she's removed over 1,300 healthy appendixes since 1996. (When "incidental" that refers to a normal-appearing appendix at the time of surgery.) Researchgate - Sohaib Khan Aga Khan University, Pakistan Any role of prophylactic appendectomy in patients with incidental appendicolith on CT scans? http://www.researchgate.net/post/Any_role_of_prophylactic_appendectomy_in_patients_with_incidental_appendicolith_on_CT_scans
474 Because women aren't dying from the removal, let's take out health appendixes during hysterectomy, not knowing why it's there or what it does. Am J Obstet Gynecol. 2003 Dec;189(6):1563-7; discussion 1567-8. The safety of incidental appendectomy at the time of abdominal hysterectomy. Salom EM1, Schey D, Peñalver M, Gómez-Marín O, Lambrou N, Almeida Z, Mendez L. http://www.ncbi.nlm.nih.gov/pubmed/14710065
475 Which CPT codes to use to get away with billing for an incidental appendectomy at the time of hysterectomy Former ACOG dept of coding and nomenclature manager MELANIE WITT, RN, CPC, COBGC, MA Ms. Witt is an independent coding and documentation consultant and former program manager, department of coding and nomenclature, American Congress of Obstetricians and Gynecologists. http://www.obgmanagement.com/home/article/elective-laparoscopic-appendectomy-in-gynecologic-surgery-when-why-and-how/925184da80c36143a0c043d1abbbc084.html
476 "An incidental appendectomy at the time of benign gynecologic procedures does not increase postoperative complication rates or length of hospital stay. The inclusion of incidental appendectomies in all abdominal hysterectomies could potentially decrease the morbidity and mortality rates because of appendicitis in elderly women." pubfacts.com - The safety of incidental appendectomy at the time of abdominal hysterectomy. Am. J. Obstet. Gynecol. Am J Obstet Gynecol 2003 Dec;189(6):1563-7; discussion 1567-8 Emery M Salom, Dana Schey, Manuel Peñalver, Orlando Gómez-Marín, Nicholas Lambrou, Zoyla Almeida, Luis Mendez http://www.pubfacts.com/detail/14710065/The-safety-of-incidental-appendectomy-at-the-time-of-abdominal-hysterectomy.
477

Elderly women are not suffering from appendicitis.

"The incidence of appendicitis in a population of 1.07 million is estimated based on discharge rates compiled by the Central Bureau of Statistics for the years 1977 and 1978. A crude incidence rate of 140 per 100,000 inhabitants is found with a male dominance (153 v. 126). The lowest incidence rate is found in the age group 0-4, whereas the highest rates are found for patients 15-24 years of age. Seventy-four per cent of all appendicitis cases is found in the age group 5-34 years. The mean length of stay was 6.5 days, but with differences between the counties studied of up to 60%. A yearly death rate of 0.30-0.37% with a male dominance is revealed."

Postgrad Med J. 1984 May; 60(703): 341–345. PMCID: PMC2417863 Appendicitis--a study of incidence, death rates and consumption of hospital resources. O. Søreide http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2417863/
478 "Two years ago, Duke University Medical Center researchers said that the supposedly useless appendix is actually where good gut bacteria safely hide out during some unpleasant intestinal conditions. Now the research team has looked at the appendix over evolutionary history. They found that animals have had appendixes for about 80 million years. And the organ has evolved separately at least twice, once among the weird Australian marsupials and another time in the regular old mammal lineage that we belong to." Scientific American - That's No Vestigial Organ, That's My Appendix A study in the Journal of Evolutionary Biology finds that many more animals have appendixes than was thought, and that the appendix is not merely a remnant of a digestive organ called the cecum. All of which means that the appendix might not be so useless. Steve Mirsky http://www.scientificamerican.com/podcast/episode/thats-no-vestigial-organ-thats-my-a-09-08-24/
479 Incidental appendectomy at time of endoscopic surgery - endometriosis, etc JSLS. 2009 Jul-Sep; 13(3): 376–383. PMCID: PMC3015983 Incidental Appendectomy During Endoscopic Surgery Jonathan Y. Song, MD,corresponding author Edgardo Yordan, MD, and Carlos Rotman, MD http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015983/
480 Incidental appendectomy is done 12X more in women than in men though lifetime risk for acute appendicitis: 8.6% risk for males, 6.7% for females (Rothrock et al, 2000). Deaths from Acute Appendicitis: 390 deaths reported in USA 1999 for appendix conditions (NVSR Sep 2001) Am J Epidemiol. 1990 Nov;132(5):910-25. The epidemiology of appendicitis and appendectomy in the United States. Addiss DG1, Shaffer N, Fowler BS, Tauxe RV. http://www.ncbi.nlm.nih.gov/pubmed/2239906
481 Should we remove the appendix when we're in there anyway? What surgical approach is best? OB Management, March 2013 · Vol. 25, No. 3:
Elective laparoscopic appendectomy in gynecologic surgery: When, why, and how This operation may be beneficial in certain populations of women, provided the surgeon has the necessary expertise and counsels the patient thoroughly before proceeding March 2013 · Vol. 25, No. 3 Teresa Tam, MD Dr. Tam is a Fellow in the Division of Urogynecology and Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania. Gerald Harkins, MD
http://www.obgmanagement.com/specialty-focus/codingbilling/article/elective-laparoscopic-appendectomy-in-gynecologic-surgery-when-why-and-how/925184da80c36143a0c043d1abbbc084.html
482 OBGYNs are not trained to perform appendectomies which are best left to general surgeons. There are no append mins in their accreditation. Healthpages.org - What Kind of Surgeon? March 17, 2015 By Cindy Schmidler http://www.healthpages.org/surgical-care/what-kind-surgeon/
483 CPT coding for removing a healthy appendix at hysterectomy Supercoder - I need help in deciding how to bill for a problematic appendectomy: https://www.supercoder.com/my-ask-an-expert/topic/appendectomy
484 Since 1980s have been recommending against removing appendix at same time as gall bladder surgery because it increases risk Am Surg. 1987 Oct;53(10):553-7. Incidental appendectomy with cholecystectomy: is the increased risk justified? Andrew MH1, Roty AR Jr. http://www.ncbi.nlm.nih.gov/pubmed/3674597
485 The role of the appendix is likely to store healthy bacteria that the body can use to repopulate the gut if a pathogen gets rid of healthy bacteria Journal of Theoretical Biology Volume 249, Issue 4, 21 December 2007, Pages 826–831 Cover image Biofilms in the large bowel suggest an apparent function of the human vermiform appendix R. Randal Bollingera, b, Andrew S. Barbasa, Errol L. Busha, Shu S. Lina, b, William Parker http://www.sciencedirect.com/science/article/pii/S002251930700416X
486 Simple explanation of roles of amyloid (protein fragment) plaques and Bright Focus Foundation - Alzheimer's - Amyloid Plaques and Neurofibrillary Tangles http://www.brightfocus.org/alzheimers/infographic/amyloid-plaques-and-neurofibrillary-tangles
487 Activin affects both stromal cells and keratinocytes in normal and wounded skin and the effect on keratinocytes is dose-dependent in vivo. Am J Pathol. 2005 Sep;167(3):733-47. Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes. Bamberger C1, Schärer A, Antsiferova M, Tychsen B, Pankow S, Müller M, Rülicke T, Paus R, Werner S. http://www.ncbi.nlm.nih.gov/pubmed/16127153
488 The tie between type ii diabetes and Alzheimer's - Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the 'metabolic syndrome', a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially 'toxic' glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself. Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? (PMID:16246041) Abstract Citations BioEntities Related Articles External Links Biessels GJ, Kappelle LJ, Utrecht Diabetic Encephalopathy Study Group Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands. g.j.biessels@neuro.azu.nl Biochemical Society Transactions [2005, 33(Pt 5):1041-1044] Type: Journal Article, Review, Research Support, Non-U.S. Gov't DOI: 10.1042/BST20051041 http://europepmc.org/abstract/med/16246041
489 The tie between type ii diabetes / metabolic syndrome / insulin resistance & Alzheimer's - Insulin plays an important role in memory and other aspects of brain function. The insulin resistance syndrome, characterized by chronic peripheral insulin elevations, reduced insulin activity, and reduced brain insulin levels, is associated with age-related memory impairment and Alzheimer's disease (AD). Our work has focused on specific mechanisms through which this association is forged, including the effects of peripheral hyperinsulinemia on memory, inflammation, and regulation of the β-amyloid peptide that plays a key role in AD pathophysiology. Our data suggest that excessive insulin invokes synchronous increases in levels of Aβ and inflammatory agents, effects that are exacerbated by age and obesity. This constellation of events may have deleterious effects on memory. Treatments focused on preventing or correcting insulin abnormalities may be of therapeutic benefit for adults with age-related memory impairment and AD. Neurobiology of Aging Volume 26, Issue 1, Supplement, December 2005, Pages 65–69 Supplement: Aging, Diabetes, Obesity, Mood and Cognition, 'SPARK' Workshop Cover image Insulin resistance syndrome and Alzheimer's disease: Age- and obesity-related effects on memory, amyloid, and inflammation Suzanne Craft, http://www.sciencedirect.com/science/article/pii/S0197458005002307
490 Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid β protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Increased Risk of Type 2 Diabetes in Alzheimer Disease Juliette Janson12, Thomas Laedtke1, Joseph E. Parisi2, Peter O’Brien3, Ronald C. Petersen4 and Peter C. Butler5 + Author Affiliations 1Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 2Department of Pathology, Mayo Clinic, Rochester, Minnesota 3Department of Biostatistics, Mayo Clinic, Rochester, Minnesota 4Department of Neurology and Health Sciences Research, Mayo Clinic, Rochester, Minnesota 5Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California Address correspondence and reprint requests to Dr. Peter C. Butler, Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, BMT-B11, Los Angeles, CA 90033. E-mail: pbutler@usc.edu http://diabetes.diabetesjournals.org/content/53/2/474.short
491 When proteins change their structure and clump together, formation of amyloid fibrils and plaques may occur. Such 'misfolding' and 'protein aggregation' processes damage cells and cause diseases such as Alzheimer's and type 2 diabetes. A team of scientists have now developed molecules that suppress protein aggregation and could pave the way for new treatments to combat Alzheimer's, type 2 diabetes and other cell-degenerative diseases. Science Daily - Amyloid plaques in Alzheimer's, diabetes: Novel leads for inhibitors Design of inhibitors of amyloid formation Date: September 24, 2015 Source: Technical University of Munich (TUM) http://www.sciencedaily.com/releases/2015/09/150924124038.htm
492 Our study identifies emergence of AD pathology in brain and retina as a major consequence of diabetes; implicating dysfunctional insulin signaling in late-onset AD, and a potential relationship between Aβ-derived neurotoxins and retinal degeneration in aging and diabetes, as well as AD. AD-type pathology demonstrated in genetically unmodified rabbits calls attention to the considerable potential of the model for investigation of AD pathogenesis, diagnostics, and therapeutics. J Alzheimers Dis. 2012;32(2):291-305. doi: 10.3233/JAD-2012-120571. Amyloid-β and tau pathology of Alzheimer's disease induced by diabetes in a rabbit animal model. Bitel CL1, Kasinathan C, Kaswala RH, Klein WL, Frederikse PH. http://www.ncbi.nlm.nih.gov/pubmed/22785400
493 Activin and inflammation, wound repair. J Endocrinol. 1999 May;161(2):187-93. A novel role of activin in inflammation and repair. Munz B1, Hübner G, Tretter Y, Alzheimer C, Werner S. http://www.ncbi.nlm.nih.gov/pubmed/10320815
494 The distribution of activins and activin receptors in the wound suggests multiple autocrine and paracrine activities of the ligands during wound healing. Our data provide evidence for a novel function of activin and indicate that--besides TGF beta s themselves--other members of this superfamily might also play an important role in tissue repair. Dev Biol. 1996 Feb 1;173(2):490-8. Strong induction of activin expression after injury suggests an important role of activin in wound repair. Hübner G1, Hu Q, Smola H, Werner S. http://www.ncbi.nlm.nih.gov/pubmed/8606007
495 "Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis,[3] metabolism, homeostasis, immune response, wound repair,[4] and endocrine function." Wikipedia - activin and inhibin https://en.wikipedia.org/wiki/Activin_and_inhibin
496 Role of inhibin in regulating FSH and to a lesser extent LH Human Reproduction Vol.17, No.10 pp. 2535–2539, 2002 Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women S.Muttukrishna 1,4,6 , S.Sharma 2 , D.H.Barlow 1 , W.Ledger 1,5 , N.Groome 3 and M.Sathanandan http://humrep.oxfordjournals.org/content/17/10/2535.full.pdf
497 Alzheimer's disease, Parkinson's, Type II Diabetes Wikipedia - List of diseases featuring amyloids https://en.wikipedia.org/wiki/Amyloid
498 "In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified." Exp Gerontol. 2001 Aug;36(8):1403-12. Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects. Baccarelli A1, Morpurgo PS, Corsi A, Vaghi I, Fanelli M, Cremonesi G, Vaninetti S, Beck-Peccoz P, Spada A. http://www.ncbi.nlm.nih.gov/pubmed/11602213
499 In patients with rheumatoid arthritis both the HPG and the HPA axis have been reported to respond abnormally to inflammation and stress. The important question of whether inflammation decreased the HPA axis (increasing risk for RA) and if correction occurs with therapy, was not answered. As pointed out by Masi et al., one needed to be able to calculate baseline levels for these hormones prior to onset of disease to be able to answer this question. When treated with DMARDS those males who responded with decreased activity of disease (measured by DAS 28 and HAQ) also demonstrated significantly increased levels of testosterone. Changes in testosterone levels in patients more than 50 years were marginally better after DMARD treatment and LH levels in both groups were unchanged (although lower in men > 50). The consequence was improvement of the hypothalamic-pituitary-gonadal (HPG) axis at the gonadal level but not the hypothalamic-pituitary-adrenal (HPA) level. Medscape - Current Opinion in Rheumatology Rheumatic Manifestations of Endocrine Diseases Joseph A. Markenson Disclosures Curr Opin Rheumatol. 2010;22(1):64-71. http://www.medscape.com/viewarticle/713289_15
500 Pituitary affects serum inhibin but not serum activin in women with ovaries Clin Endocrinol (Oxf). 1996 Dec;45(6):741-8. Circulating inhibins and activin A during GnRH-analogue down-regulation and ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo transfer. Lockwood GM1, Muttukrishna S, Groome NP, Knight PG, Ledger WL. http://www.ncbi.nlm.nih.gov/pubmed/9039341
501 PATHOPHYSIOLOGY COURSE - ENDOCRINE MODULE Male Gonadal Disorders (Testicular Disorders & Clinical Conferences) Dale Childress, MD Monday, December 6, 2010 , 8:00 - 8:50am Written by: Jeffrey R. Gingrich, M.D. Goals and Objectives: 1. To understand regulation of the hypothalamic - pituitary - gonadal axis. 2. To become familiar with the etiologic categories of testicular endocrine disorders. 3. To learn the appropriat e diagnostic evaluation and interpretation of laboratory results for patients with testicular endocrine disorders. I. THE HYPOTHALAMIC - PITUITARY - GONADAL AXIS An understanding of the reproductive axis is critical for the assessment of abnormal develo pment of the genitalia (e.g. pseudohermaphroditism), hypergonadism, hypogonadism, infertility and erectile dysfunction. The reproductive hormonal axis in men consists of three main components: (A) the hypothalamus, (B) the pituitary gland, (C) the testis. Regulation of this axis impacts on the steroid - sensitive end organs such as the prostate and penis. This axis normally functions in a tightly regulated manner to produce concentrations of circulating steroids required for normal male sexual development, se xual function and fertility. ATHOPHYSIOLOGY COURSE - ENDOCRINE MODULE Male Gonadal Disorders (Testicular Disorders & Clinical Conferences) Dale Childress, MD Monday, December 6, 2010 , 8:00 - 8:50am Written by: Jeffrey R. Gingrich, M.D. https://www.uthsc.edu/endocrinology/documents/ch08-syllabus-Childress.pdf
502 Women who are more than 10 years postmenopause and who have had their ovaries removed lose bone mineral density (BMD) at twice the rate of those who have kept their ovaries and show greater progression in the thickening of the carotid artery. These findings, which will be published in Fertility and Sterility, indicate that oophorectomy appears to put women at higher risk for developing both osteoporosis and cardiovascular disease (CVD). The researchers found that the rate of subclinical atherosclerosis progressed faster in those having undergone oophorectomy when compared with their ovary-retaining counterparts. CIMT progression and BMD loss were worse in those women greater than 10 years postmenopause who had undergone oophorectomy. OBGYN.net - Oophorectomy Increases Risk of Osteoporosis and Cardiovascular Disease News | February 17, 2014 | Menopause, Hysterectomy, Laparoscopy, Surgical Gynecology By OBGYN.net Staff http://www.obgyn.net/menopause/oophorectomy-increases-risk-osteoporosis-and-cardiovascular-disease
503 ACTIVIN

Box 1. Glossary – Immune cells that are affected by activin

B cells: lymphocytes governing a humoral (antibody-mediated) immunity.

Dendritic cells: immune cells that process antigens and present them on their surface to other cells of the immune system, thereby initiating an immune response.

Dendritic epidermal T cells (DETCs): a subpopulation of T cells present in the murine epidermis; they express γδ T cell receptor and are involved in regulating epidermal homeostasis, inflammation, wound repair and tumour surveillance.

Langerhans cells: dendritic cells of the skin and mucosae contiguous with skin (mouth, foreskin, vagina).

Macrophages: phagocytic cells that engulf and digest cellular debris and pathogens; they acquire different activation states (e.g. M1 or M2) and function in innate and adaptive immunity, and in the regulation of inflammation and tissue repair.

Mast cells: resident immune cells populating most tissues, especially frequent in the skin and mucosae; they mainly function in allergic reactions and in response to helminthes, but are also involved in modulating inflammation, wound repair and carcinogenesis.

Myeloid-derived suppressor cells: heterogeneous population of immature myeloid cells that expands during cancer, inflammation and infection; they potently suppress natural killer (NK) and T cell responses and have been implicated in tumour-associated immune suppression.

Natural killer cells (NK cells): cytotoxic lymphocytes that are part of the innate immune system; in particular, they kill virus-infected cells and tumour cells.

Regulatory T cells (Tregs): a type of T cell that suppresses the immune system, maintains tolerance to self-antigens, downregulates autoimmune disease and inhibits anti-tumour immunity.

T cells: lymphocytes, providing cell-mediated immunity; they are subdivided in subsets (Th1, Th2, Tregs, γδ T cells, etc.), each with a distinct function.

    • Structure of activins and their signalling mechanisms
    • The role of activin in wound healing
    • The role of activin in scar formation and fibrosis
    • The role of activin in cancer development
    • Role of activin in malignant progression
    • A functional role of activin in skin cancer
    • Conclusions and perspectives
    • Footnotes
    • References

 

The Company of Biologists - The bright and the dark sides of activin in wound healing and cancer Maria Antsiferova, Sabine Werner J Cell Sci 2012 125: 3929-3937; doi: 10.1242/jcs.094789 http://jcs.biologists.org/content/125/17/3929
504 The relationship of estrogen, dopamine, and Parkinson's. The Journal of Neuroscience, December 1, 2000, 20 (23):8604–8609
Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson’s Disease and Memory Csaba Leranth, 1,5 Robert H. Roth, 2,3 John D. Elswoth, 2,3 Frederick Naftolin, 1 Tamas L. Horvath, 1,5 and D. Eugene Redmond Jr 2,4 Departments of 1 Obstetrics and Gynecology, 2 Psychiatry, 3 Pharmacology, and 4 Neurosurgery and 5 Section of Neurobiology, Yale University, School of Medicine, New Haven, Connecticut 06520-8063
http://www.jneurosci.org/content/20/23/8604.full.pdf
505 Women who have had an oophorectomy are at increased risk for developing parkinsonism and Parkinson disease (PD) later in life, Mayo Clinic researchers reported here in April at the AAN Annual Meeting. Neurology Today: June 2005 - Volume 5 - Issue 6 - p 52–54 Original Article OOPHORECTOMY MAY RAISE PD RISK Laino, Charlene http://journals.lww.com/neurotodayonline/Fulltext/2005/06000/Oophorectomy_May_Raise_Pd_Risk.20.aspx
506

Glaucoma - second leading cause of blindness

Patients with glaucoma had a different HPA response to vasopressin.

"With vasopressin, a decreased response of plasma cortisol levels was negatively correlated with the degree of elevated ocular pressure. Those subjects with increased ocular pressure and lower tonographic outflow facilities had smaller rises of plasma cortisol levels. Both tests indicated a disturbance of the hypothalamic-pituitary-adrenal axis in subjects with glaucoma."

Arch Ophthalmol. 1981 Oct;99(10):1770-7. Differences of adrenal stress control mechanisms in subjects with glaucoma and normal subjects. Effect of vasopressin and pyrogen. Schwartz B, Golden MA, Wiznia RA, Miller SA. http://www.ncbi.nlm.nih.gov/pubmed/7295125
507 Aldosterone (adrenal product) proven to regulate retinal cell death that accompanies glaucoma Cell Death Dis. 2013 Jul 4;4:e711. doi: 10.1038/cddis.2013.240. Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma. Nitta E1, Hirooka K, Tenkumo K, Fujita T, Nishiyama A, Nakamura T, Itano T, Shiraga F. http://www.ncbi.nlm.nih.gov/pubmed/23828574
508 More proof of the correlation between testosterone and insulin sensitivity, type II diabetes, and obesity. Testosterone is a metabolic hormone. Also 90% of men on dialysis have low testosterone. " Testosterone did not change the men's body weight, but there was a reduction in total body fat of 3 kilograms (more than 6 pounds), while muscle mass increased by the same amount. There was also a dramatic increase in insulin sensitivity, demonstrated by a 32% increase in the uptake of glucose by tissues in response to insulin, and a similar increase in the expression of the major genes that mediate insulin signaling. " Medical News Today - Could testosterone therapy benefit men with type 2 diabetes? Published: Monday 30 November 2015 at 1am PST http://www.medicalnewstoday.com/articles/303291.php
509 Testosterone therapy in women - not experimental. Provides dosage guidelines, its role in reduction of breast cancer, and benefit to depression, bone, brain, cardiac, memory, vascular tissue, fat, muscle. Testosterone Hormone Therapy with Pellet Implants for Women Adapted from an article by Rebecca Glaser http://www.myhormonetherapy.com/wp-content/uploads/2012/06/Testosterone-Therapy-for-Women.pdf
510

A Message From Dr. Cutler:

When I was working at the University of Pennsylvania with my mentor, Professor of Gynecology, Chief of Reproductive Endocrinology Dr. Celso-Ramon Garcia, in the late 1970s and early 1980s, I asked him why healthy ovaries were routinely being removed at hysterectomy in woman over 40 years of age. He told me that ovarian cancer risks caused medical schools to teach ovariectomy as a good medical practice.

I asked how often do women get ovarian cancer? And is there any relationship between a non cancer condition in the uterus, and the likelihood of subsequently developing ovarian cancer? Dr. Garcia had been taught that there was evidence to suggest that women were better off having healthy ovaries removed while a surgeon had easy access to them during a hysterectomy.

We decided to investigate and our search of published papers led us to conclude that the “evidence” had been based on a grammatical error. The literature had been misquoted.

Our research further suggested that the studies recommending ovariectomy were erroneous. We concluded that the ovary does contribute to the hormonal well-being of women past their reproductive years and should be left intact especially during hysterectomy if possible. Dr. Garcia insisted I write the first draft of our discovery and we worked together to produce the following paper, published in 1984. By 1986 he was excited to tell me that half of the medical schools in the US had changed their suggestions and were now recommending a reconsideration of the common practice of ovariectomy.

- - Winnifred Cutler, Ph.D. Athena Institute 2004

INTRODUCTION:

The incidence of routine ovariectomy approximates 20% to 30% of all women at hysterectomy. The propriety of this practice is evaluated from three perspectives: (1) the review of the longevity of ovarian hormonal function throughout life, (2) the review of the low risk of subsequent disease in the retained ovary, and (3) the review of epidemiologic considerations. Because oophorectomy and the loss of its steroid contribution has such a profound influence on many body functions, with the most devastating relation to osteoporosis, and because there are no meaningful data in the literature to support the value of routine oophorectomy, removal of ovaries should only be performed when the ovaries are diseased.

The 1980’s have been viewed as a time when greater efforts must be directed toward improving the health and welfare of the maturing female. A reappraisal of our attitudes concerning routine oophorectomy and its implication in the welfare of the female is mandatory. The gynecologist frequently is required to decide between ovarian preservation versus ablation, particularly when hysterectomy is performed for benign disease.

This is a significant problem, because the current incidence of hysterectomy in the United States approaches 60% by the time women reach 65 years of age. In the younger woman, the consensus is almost always favored, namely, ovarian preservation.

On the other hand, in the women past 40, the reverse is usually true – routine ovariectomy. The gynecologist performing a hysterectomy is concerned with the potential of malignant transformation in the preserved ovary or ovaries, which could be a deadly prospect. Nonetheless, removing the ovaries in an ovulating woman deprives her of significant hormonal support, which often is difficult to replace adequately.

The question of the propriety of routine ovariectomy during hysterectomy is best evaluated form four perspectives: (1) the review of the longevity of ovarian function, (2) the risk of subsequent disease in the retained ovaries, (3) a consideration of current data on ovariectomy, and (4) the epidemiologic considerations.

LONGEVITY OF OVARIAN FUNCTION:

While it has been commonly stated that ovaries become essentially nonfunctional sometime after the mid-40s, the accumulated weight of evidence supports the appropriateness of reexamining this long-held view.

As the ovary ages, it continues to contribute to the steroidal milieu of the menopausal woman, albeit in a declining fashion. As early as 1965, Novak et al1.. Had shown that postmenopausal ovaries frequently maintained a steroid capability for several decades after menses had ceased.

Morphologic evidence suggests that the aging ovary is quite different from the younger ovary, particularly after the cessation of ovulation.

Nonetheless, the human postmenopausal ovary is not the completely inert, nonfunctional fibrous mass that many formerly thought it to be2.

There is a gradual diminution in ovarian mass that occurs throughout the 30s and progresses more rapidly after the age of 453. The differences between the old and the young ovary, especially after age 55 are quite striking; the decreasing population density of follicular structures and a correlative increase of the stroma are evident4. Nonetheless, these older ovaries, replete with stroma material, are now understood to actively produce androstenedeione – the hormone that, in the menopausal woman, is converted to estrone, in the fat depots of the body. This pathway can be significant in preventing osteoporosis.

McNatty et al5 have shown that postmenopausal stroma function differently than premenopausal stroma. Their in vitro analysis of the production of progesterone, androgen, and estrogen showed that, in the younger ovaries, all of the ovarian compartments were active, and stromal tissue had lower levels of cellular activity, mitotic activity, and cell hypertrophy than thecal tissue. In the postmenopausal ovaries, the situation was reversed: the level of cellular activity in the stroma was quite high, and considerable hypertrophy was observed. Other evaluations of steroid production and responsiveness to gonadotropins in isolated postmenopausal stroma tissue show that cortical stroma produces measurable amounts of estradiol, and progesterone, in vitro, while hyperplastic stromal tissue yields even greater androstenedeione and estradiol6. Hormone secretion of ovaries at hysterectomy was studied by Mikhail7, who offered that menopausal ovarian vein was rich in deyhdroepiandrosterone and E1. Longcope et al.8 also reported on a spectrum of ovarian function in postmenopausal women via venous-arterial differences in studies during hysterectomy procedures.

Combining the evidence from morphologic, histochemical, in vitro steroidogenic, and ovarian vein catheter studies leads us to confirm a lifelong ovarian developmental pattern. There is a greater appreciation of relative mass toward stormily tissue with increasing age; and with this increase of stromal tissue, there results an increase in the capacity to synthesize androstenedione. The ovaries of women in the menopausal years, often late into the menopause, continue to secrete androgens which may support the well-being and general health of the older woman.

Peripheral conversions of these androgens to estrogen are well documented. Certainly the availability of these steroids for such conversion will be terminated upon oophorectomy. Consequently, perspectives on the propriety of routine ovariectomy, in the absence of ovarian disease, are being reexamines ad the evidence supporting postmenopause ovarian function accumulates. Moreover, the term “quiescent ovary” used to describe all older ovaries, is no longer justifiable.

POST- HYSTERECTOMY OVARIAN ACTIVITY

The incidence of retention of ovarian cyclicity after hysterectomy remains somewhat unclear. The majority of posthysterectomy patients under age 48 continue to show an ovarian cycle, according to any of several criteria: bioassay of weekly urine samples9, cyclic records of premenstrual tension phenomenon10, plasma hormone evaluation, and studies of vaginal smears11. However, the phenomenon appears to be less than universal. Ranny and Abu-Ghazaleh12 evaluated the future function and control of ovarian tissue that is retained in vivo during hysterectomy and concluded that approximately 50% of their large sample continued to show clinical signs of ovarian hormone production (i.e. vaginal tissue maintenance) but the other 50% did not. This was the only study of those just described that sampled very large groups of women; and these results, therefore, suggest that some women stop showing ovarian cyclicity shortly after hysterectomy.

The nature of influence of an intact uterus on ovarian function is currently unresolved; but with recent discovery of uterine secretions of large quantities of prostaglandins, there is reason to study the issue13.

Potentially, the reduction in prostaglandin after hysterectomy could be a factor in the loss of ovarian cyclicity. Alternatively, the loss of the putative reflex pathway from cervix to pituitary (as is found in lower mammals)14could also be responsible.

POST OOPHORECTOMY ENDOCRINE ACTIVITY

Studies of ovariectomized women before, immediately postoperatively, and at various time intervals after surgery have been generally consistent. Both gonadotropin predictably show a rapid rise, which, by 3 weeks, can easily have reached 10 times preoperative levels 15, 16. Likewise within 3 hours, estrogen drops to 60% of the presurgical level17, reaches a nadir by 5 days after surgery,18 and levels off thereafter at the new lower values.

Hormone replacement therapy does somewhat reduce these gonadotropin/steroid levels. Follicle-stimulating hormone more closely approaches its preoperative levels15,19. In one study, luteinizing hormone changes required a combination estrogen and progestin hormone therapy15. E2 levels in plasma increase to preoperative levels when estrogen replacement therapies are sufficiently concentrated19. However, no estrogen dose is able to equilibrate both the gonadotropins and the steroids at the preoperative equivalency in women 45 to 53 years old. In order to reduce gonadotropins to preoperative levels, one must produce a hyperestrogenic state19. The ovarian hormones, then, probably include other substances, which are not replaced by estrogen or progestins.

Oophorectomized women frequently experience hot flushes, and studies have shown that those women who do flush postoperatively have significantly lower (A) levels than those women who do not17 – another reflection of the value of preservation of the ovaries.

Also noteworthy is the significant decline in epidermal thickness that follows oophorectomy at any age20. This epidermal thickness can be restored, or the decline prevented, by a weak estrogen (estriol succinate, 2 mg/day); whereas a stronger estrogen (estradiol valerate, 2 mg/day) sometimes produces the opposite effect21. The most critical issue, however, is loss of bone mass leading to osteoporosis, which oophorectomy is known too initiate. It is relevant to know that lowered E1 and (A levels are established risk factors for osteoporosis. In contrast E2 , and testosterone concentrations have not been identified as significant in assessing the osteoporosis risk factors.22

 

RISK OF SUBSEQUENT OVARIAN DISEASE:

Benign Ovarian Tumors:

Varying types of ovarian tumors may be encountered – each having its distinct anatomic and clinical properties23-26. A knowledge of gross anatomic disease aided by the histologic capabilities of the pathologist, particularly via frozen section, may be most helpful in deciding whether oophorectomy or simple resection of the pathologic portion – e.g. endometriosis, benign cystic teratomas etc – is sufficient.

Malignant Ovarian Tumors:

The incidence of ovarian cancer varies markedly with age. In a study of the epithelial cancer rates of the ovary in over 2000 cases at the M.D. Anderson Hospital 27, it was found that the peak years for this cancer are the 40s to the late 60s paralleling the time during which estrogen levels are declining most precipitously. In that study, the wealthy had a lower survival rate that postoperative chemotherapy. As therapeutic techniques change, reevaluation will, no doubt, alter this perspective. The size of the largest remaining cancer mass in the body was more predictive of survival than the number of focal malignant sites. Interestingly enough, despite the present consensus to the contrary, the spillage of cystic contents of the mass at surgery did not lower the survival rate. Five –year survival rates were also noted to vary considerably as a function of age. Survival rates decrease with age.

The fact that ovarian cancer was so resistant to treatment led to the routine removal of perfectly healthy ovaries under the assumption that such action would prevent potential ovarian cancers. However, the presently available data do not support the logic of this course.

EPIDEMIOLOGIC CONSIDERATIONS:

The risk of ovarian cancer in women in whom hysterectomy was contemplated for benign uterine disease has now been studied in two different ways. One can look at the ovarian cancer patients and compare them with patients who have not undergone prior ovarian ablation. Once can ask what the hysterectomy rate was for each population. If it were dangerous to retain the ovaries after a hysterectomy, one would expect to find a higher frequency of formerly hysterectomized women among ovarian cancer patients that among those without ovarian cancer. The opposite is true. Studies have consistently show that ovarian cancer patients have a much lower incidence of hysterectomy than is found in the general population. For example, Annegers et al28. Reported a 5 % prior hysterectomy rate in ovarian cancer patients, compared with a 23% hysterectomy rate in age-matched women who had not undergone prior ovariectomy. Two other studies published in the 1950s showed a similarly low 4% and 4.5%30 rate of prior hysterectomy among the ovarian cancer patients. Unfortunately, even though these data are quiet clear in showing that hysterectomy in ovarian cancer patients is disproportionately lower, misleading logic has been applied for the reverse conclusion31, i.e., that ovaries should be removed at hysterectomy. This incorrect conclusion has been widely cited and, thereby, a false premise perpetuate.

Another line of investigation also supports the safety of retaining the ovaries at hysterectomy. Prospective rates of ovarian cancer in ovaries retained after hysterectomy also support the absence of a risk32. A cohort study following 900 hysterectomized women for 20 years showed an overall rate of subsequent ovarian cancer at 0.2% in the sample32. The women who had both ovaries preserved showed a much lower rate (0.01%) of subsequent cancer than those who had only one ovary preserved (0.3%).

There is, therefore, a consistent and clear picture when we scrutinize the data rather than analyzing the published conclusions. The goal of surgical prevention of ovarian cancer should not conclude in a decision for oophorectomy at hysterectomy. In fact, in 1982, a report of intraabdominal carcinomatosis (indistinguishable from ovarian carcinomatosis) after prophylactic oophoroctomy in ovarian cancer-prone families showed the futility of such a course33.

Oophorectomies were performed “prophylactically” on 28 members of 16 families that were at high risk of ovarian carcinoma. Three of these women subsequently developed disseminated intraabdominal malignancy33 The authors concluded that the development of intraabdominal carcinomatosis in oophorectomized women from ovarian cancer-prone families suggests that genetic susceptibility is not limited to ovarian carcinoma but extends to cnancers arising in tissues embryologically related to the ovary. It should be pointed out that the incidence of ovarian cancer is extremely low. There appears, therefore, dubious advantage to be gained by the routine removal of healthy ovaries at hysterectomy.

In spite of what appears to be a rather clear case against routine ovariectomy during hysterectomy, current surgical practice has been different. Using data from the National Center for Health Statistics, Dicker et al34. evaluated women ranging in age from 25 to 44 during the interval of 1970 to 1977.

They reported that ovariectomy during hysterectomy for benign causes was occurring about 25% of the time and did not change throughout the years the data were collected. Older women, the group from 40 to 44, had an approximate 50% rate of ovariectomy at hysterectomy. In light of currently available knowledge demonstrating hormone secretion by ovaries in the 40s, 50s, and 60s, (particularly A) the value of such hormones in reducing the risk of osteoporosis, and the lack of advantage in preventing ovarian cancer by oophorectomy, the routine practice of oophorectomy is challenged.

While those who have inadequate sources of androgen or peripheral conversion capacity may benefit from hormonal replacement, there remain a significant (15%) number who do not require hormonal support. Not only will oophorectomy most often be ineffective in preventing ovarian cancer; but, more important, the loss of these ovarian secretions may play a role in producing the degenerative sequence of osteopenia and osteoporosis. This pathophysiologic sequence of osteoporosis can be more often favorably modified by estrogen hormonal replacement therapy. The osteoporotic process has recently been reviewed35.

Nonetheless, some osteoporotic patients are resistant to these normally effective measures, as is sometimes the case in the relief of some of the other postemenopausal symptoms. The evidence continues to support the theory that ovaries should be retained unless they are diseased.

CONCLUSIONS:

In the face of the exceedingly low incidence of ovarian cancer and its questionable prevention by prophylactic oophorectomy, routine oophorectomy would deprive enormous numbers of women of the essential benefits afforded by these steroid-secreting organs. One exception might be the case of familial ovarian carcinoma syndrome33,36-38.

Clearly, in such an instance, the patient must be properly informed of all options and considerations, including the possibility of subsequent disseminated peritoneal carcinomatosis in some even after oophorectomy. Because oophorectomy has such profound influences at every age, particularly its devastating relation to osteoporosis, and because there are no meaningful data I the literature to support the value of routine oophorectomy, we suggest that oophorectomy only be performed when the ovaries are diseased.

LETTER TO THE EDITOR & AUTHORS' REPLY:

To the Editor:

We would like to thank Doctors Garcia and Cutler for their very provocative paper. It certainly has caused those with interests in reproductive endocrinology and gynecology oncology to reevaluate the management of the ovary in conjunction with a hysterectomy in women over 40 years of age.

It is a given well-established, and well-documented fact that the ovary may produce hormones well into the sixties, acting after menopause primarily as an androgen-producing organ, and causing, through peripheral conversion, the production of estrone. We know, though, because osteoporosis and other stigmata develop in postmenopausal women because of the relatively insufficient quantities of estrogen, that this hormonal production is virtually ineffective. Therefore, one must conclude that there is no strong reason to leave the ovary intact at the time of hysterectomy with the aim being production of effective hormonal substances in the menopausal years.

The question, with regard to castrating the woman in her fifth decade, is not whether her ovaries will function effectively in the postmenopausal years, but whether they will function in the years between castration and menopause. There is definite controversy as to whether the ovary continues to function normally after hysterectomy because of a compromised blood supply. Nevertheless, the critical question, is whether leaving the ovary in at the time of hysterectomy has sequelae with regard to future benign and malignant ovarian disease.

Ovarian cancer is the major cancer health hazard for the female pelvic reproductive organs. There will be more deaths this year form ovarian cancer than total deaths from cervical and endometrial cancer combined. Recent epidemiologic studies suggest that the a patient at highest risk for developing ovarian cancer is a middle or upper class white woman who is nulliparous or of low parity.

In evaluating Garcia and Cutler’s proposed evidence to support leaving the ovaries behind in women undergoing hysterectomy, one can only wonder how many women cited in their supporting references and operated on in the 1930s and 1950s actually fell into the high risk group for ever developing ovarian cancer. One must be skeptical about white nulligravidas or women of low parity constituting the overwhelming majority of these patients. Unfortunately, this sort of epidemiologic data is not available in the studies quoted by the authors. Pure familial ovarian cancer syndromes are rare. One must be very skeptical about the three cases cited by the authors as being typical of common epithelial cancer of the ovary. One of the latter patients died with brain metastases, and a second one died 2 months after diagnosis with metastases to the liver and subcutaneous tissue; clearly these are highly virulent cancers. Additional questions have been raised about whether sections of the ovaries from these three patients were adequate to rule out microscopic disease at the time of prophylactic oophorectomy.

The concept of leaving a visibly normal ovary behind in a woman aged 40 to 50, as suggested by the authors, when the contrallateral ovary is involved with a ‘benign process” such as endometriosis or a benign teratoma is simply not good clinical judgment. The concept of performing frozen section analysis on the normal ovary when a benign tumor is present in the ovary may potentially compromise ovarian function further in women aged 40 to 50. Routine use of frozen section analysis of all ovaries to be left intact at the time of hysterectomy would be extremely expensive and would involve an inherent risk of missing microscopic disease.

In conclusion, there seems to be no need to leave a perimenopausal or postmenopausal ovary in situ even though it continues to function for perhaps 10 or even 20 years. The hormonal function is ineffective in preventing postmenopausal symptoms. Ovarian neoplasm remains a major health hazard for these women. Satisfactory estrogen and progesterone replacement in women over 40 is a reality. Each adversarial side awaits more and better information.

Alan H. DeCherney, M.D.
Peter E. Schwartz, M.D.
Department of Obstetrics and Gynecology
Yale University of School of Medicine
New Haven, CT 06510-8063
August 20, 1985

References for this Letter to the Editor:
1. Garcia, C-R, Cutler WB: Preservation of the ovary: a reevaluation. Fertil Steril 42:510, 1984
2. Janson PO, Jansson I: The acute effect of hysterectomy on ovarian blood flow. Am J Obstet Gynecol 127:349, 1977
3. Stone SC, Dickey RP, Mickal A: The acute effect of hysterectomy on ovarian function. Am J Obstet Gynecol 117: 193, 1973

Reply of the Authors Garcia and Cutler (To DeCherney, Schwarcz letter)

Until improvements in therapy are more evolved, our colleagues should be cognizant of the hazards and risks of ovariectomy and the all too frequent potential inability to correct for the missing ovarian hormones by replacement regimens.

A. Their statement :"...because osteoporosis...develop(s) in postmenopausal women...this (ovarian post-menopausal) hormonal production is virtually ineffective. Therefore, one must conclude that there is no strong reason to leave the ovary intact..."

In reply

1. Removing the source of a significant production of estrone (whether through estradiol conversion into estrone in the younger woman or androstenedione conversion into estrone in the mature ovary), (1) ignores the fact that 40% of women do not experience the development of osteoporosis and (2) increases the risk of metabolic bone disease for those 60% who are subject to osteoporosis. McNatty demonstrated that stromal tissue from a menopausal ovary contains more androstenedione, and its conversion product, estrone, are much more relevant as risk factors than estradiol or other identified steroids correlating with the prediction of osteoporosis, even the aging ovary appears to contain a built-in mechanism to inhibit osteoporosis.

2. The use of osteoporosis as a single gauge in defining the value of aging ovaries is inappropriate. Ovarian hormones provide meaningful physiologic effects other than simply contributing to a positive bone mineral metabolism. For example, a large loss of sexual motivation (arousal, fantasy life, and desire) in oophorectomized, 46 year old women in prospective, double-blind crossover placebo -controlled trials has been shown, and the sexual motivation was found to be replaceable through androgen. Thus, although we currently do not know the precise appropriateness of androgen replacement for optimal body function, the androgen contribution of aging ovaries is acknowledged.

3. It is naive to believe that oophorectomy followed by hormonal replacement therapy does bring the patient back to the endocrine status she enjoyed prior to ovariectomy. The amount of estrogen replacement therapy currently being prescribed does not bring the gonadotropin level back to normal. Moreover, the role of ovarian androgen secretion in sexual motivation further demonstrates our currently primitive understanding of the manifold functions of the maturing ovary.

4. The degree of osteoporosis is a complex function of steroid levels (principally estrone), adequate ingestion of absorbable calcium, sufficient vitamin D, and appropriate levels of parathyroid hormone and calcitonin

5. Their statement that the critical question is the risk of ovarian cancer in retained ovaries at the time of hysterectomy.

In Reply:

1. There are no data that support that removing the ovaries is preventative of subsequent ovarian-type cancer.

2.Ovarian cancer deaths occur relatively infrequently (11,600 per year) in relation to deaths secondary to cardiovascular disease (485,000 per year) and during recovery from hip fracture.

We agree that significant ovarian disease needs to be addressed. However, gynecologic surgeons are much too prone to remove both ovaries even when there is minimal endometriosis in the pelvis where the other ovary may have minimal benign disease that can be resected or even when the ovary is normal. Resection of the endometriosis and preservation of the normal ovary is a more preferable option in protecting the general health of women even at age 40 to 50.

Physiologic age is not always compatible with chronologic age. It is obvious that it is good clinical judgement to make the correct decision about the appropriateness of retaining a normal ovary in a woman of age 40 to 50 when encountering benign disease in the pelvis. Frozen section should be used when necessary, but not routinely. However, a very superior knowledge of gross anatomic gynecologic pathology is essential. Physicians uncomfortable with their knowledge of these tissue abnormalities should not expose their patients to the increased risk of routine ovariectomy simply to ease feelings of responsibility. All the risks must be weighed appropriately.

Despite the decline in reproductive system circulating steroids being about equivalent for men and women, testes, perhaps because they are more accessible, are more reluctantly removed than are ovaries. Removal of ovaries occurs less frequently at vaginal hysterectomy than abdominal hysterectomy even with similar benign pelvic disease.

We remind those who would consider whether or not to remove an organ that is healthy that the burden of proof question ought to rest with the remover and that we should remember the dictum, "Above all, do not harm."

References to REPLY FROM AUTHORS LETTER

1. McNatty KP, Hunter WM, McNeilly AS, Sawers RS: Changes in the concentration of pituitary and steroid hormones in the follicular fluid of human Graafian follicles throughout the menstrual cycle. J.Endocrinol. 64:555, 1975

2. Sherwin BB, Gelfand MM, Brender W: Androgen enhances sexual motivation in females: a prospective crossover study of sex steroid administration in surgical menopause. Psychosom Med 47:339, 1985.

3. Vital statistics of the United States: Death statistic references

4. Cutler WB, Garcia CR: Sexuality and hormones. In The Medical Management of Menopause and Premenopause: Their Endocrinologic Basis. Philadelphia, J.B. Lippincott, 1984, p.92

 

REFERENCES TO THE PAPER,
PRESERVATION OF THE OVARY: A REEVALUATION

1. Novak ER, Goldberg B, Jones GS: Enzyme histochemistry of the menopausal ovary associated with normal and abnormal endometrium. Am J Obstet Gynecol 93:669, 1965

2. Guraya S: Histochemical observations on the corpus luteum atreticum of the human postmenopausal ovary with reference to steroid hormone synthesis: Arch Ital Anat Embriol 56:189, 1976

3. Tervila L: The weight of the ovaries after stress ending in death. Ann Chir Gynaecol Fenn 47:232, 1958

4. Nicosia SV: Morphological changes in the human ovary through life. In Comprehensive Endocrinology: The Ovary, Edited by L Martini, GB Serra. New York, Raven Press, 1983, p 57

5. McNatty KP, Makris A, DeGrazia C, Osathanondh R, Ryan KJ: The production of progesterone, androgens, and estrogens by granulose cells, thecal tissue and the stromal tissure by human ovaries in vitro. J Clin Endocrinol Metab 49:687, 1979

6. Dennefors B, Janson P, Knutson F, Hamberger L: Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries. Am J Obstet Gynecol 136:997, 1980

7. Mikhail G: Hormone secretion by the human ovaries. Gynecol Invest 1:5, 1970

8. Longcope C, Hunter R, Franz C: Steroid secretion by the postmenopausal ovary. Am J Obstet Gynecol 138:564, 1980

9. Beavis ELG, Brown JB, Smith MA: Ovarian function after hysterectomy with conservation of the ovaries in premenopausal women. J Obstet Gynaecol Br. Commonw 76:969, 1969

10. Backstrom CT, Boyle H: Persistence of premenstrual tension symptoms in hysterectomized women. Br J Obstet Gynaecol 88:530, 1981

11. DeNeef JC, Hollenbeck ZJR: The fate of ovaries preserved at the time of hysterectomy. Am J Obstet Gynecol 96:538, 1966

12. Ranney B, Abu-Ghazaleh S: The future function and control of ovarian tissue which is retained in vivo during hysterectomy. Am J Obstet Gynecol 128:626, 1977

13. Charbonnel B, Dremer M, Gerozissis K, Dray F: Human cervical mucus contains larger amounts of prostaglandins. Fertil Steril 38:109, 1982

14. Cutler WB, Garcia C-R: The psychoneuroendocrinology of the ovulatory cycle of woman. Psychoneuroendocrinology 5:89, 1980

15. Wallach EE, Root AW, Garcia C-R: Serum gonadotropin responses to estrogen and progestogen in recently castrated human females. J Clin Endocrinol Metab 31:376, 1970

16. Yen SSC, Tsai OC: The effect of ovariectomy on gonadotropin release. J Clin Invest 50:1149, 1971

17. Barlow DH, Macnaughton MC, Mowat J, Coutts JRT: Hormone profiles in the menopause. In Functional Morphology of the Human Ovary, Edited by JRT Coutts. Baltimore, University Park Press, 1981, p 223

18. Hunter DJ, Julier D, Franklin M, Green E: Plasma levels of estrogen, luteinizing hormone, and follicle-stimulating hormone following castration and estradiol implant. Obstet Gynecol 49:180, 1977

19. Utian W, Katz M, Davy D, Carr P: Effect of premenopausal castration and incremental dosage of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone and estradiol. Am J Obstet Gynecol 132:297, 1978

20. Punnonen R, Raurama L: The effect of long-term oral oestriol succinate therapy on the skin of castrated women. Ann Chir Gynaecol 66:214, 1977

21. Punnonen R: Effect of castration and peroral estrogen therapy on the skin. Acta Obstet Gynecol Scand 21:1, 1972

22. Crilly R, Horsman A, Marshal DH, Nordin BEC: Prevalence, pathogenesis and treatment of postmenopausal osteoporosis. Aust NZ J Med 9:24, 1979

23. Reed MJ, Hutton JD, Beard RW, Jacobs HS, James VH: Plasma hormone levels and oestrogen production in a postmenopausal woman with endometrial carcinoma and ovarian thecoma. Clin Endocrinol (Oxf) 11:141, 1979

24. Rome RM, Fortune DW, Quinn MA, Brown JB: Functioning ovarian tumors in postmenopausal women. Obstet Gynecol 57:705, 1981

25. Sternberg WH: The morphology , androgenic function, hyperplasia, and tumors of the human ovarian hilus cells. Am J Pathol 25:493, 1947

26. Gordon A, Rosenstein N, Parmley T, Bhagavan B: Benign cystic teratomas in postmenopausal women. Am J Obstet Gynecol 138:1120, 1980

27. Smith JP, Day TG: Review of ovarian cancer at the University of Texas Systems Cancer Center MD Anderson Hospital and Tumor Institute. Am J Obstet Gynecol 135:984, 1979

28. Annegers JF, Strom H, Decker DG, Dockerty MD, O’Fallon WM: Ovarian cancer: reappraisal of residual ovaries. Am J Obstet Gynecol 97:124, 1967

29. Smith GV: Ovarian tumors. Am J Surg 95:336, 1958

30. Counseller VS, Hunt W, Haigler FH: Carcinoma of the ovary following hysterectomy. Am J Obstet Gynecol 69:538, 1955

31. Grogen RH: Reappraisal of residual ovaries. Am J Obstet Gynecol 97:124, 1967

32. Randall CL: Ovarian conservation. In Progress in Gynecology, Edited by JV Meigs, SH Sturgis. New York, Grune & Stratton, 1963, p 457

33. Tobachman JK, Tucker MA, Kase R, Greene MH, Costa J, Fraumen JF: Intraabdominal carcinomatosis after prophylactic oophorectomy in ovarian cancer prone families. Lancet 2:795, 1982

34. Dicker R, Greenspan J, Strauss L, Cowart M, Scally M, Peterson H, DeStefano F, Rubin G, Ory H: Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States. Am J Obstet Gynecol 144:841, 1982

35. Cutler WB, Garcia C-R: Osteoporosis. In The Medical Management of Menopause and Premenopause : Their Endocrinologic Basis. Philadelphia, J. B. Lippincott Co., 1984, p 49

36. Barber HRK: Epidemiology of cancer of the ovary. In Ovarian Carcinoma, Second edition. New York, Masson Publishing, 1982, p 25

37. Lynch H, Albano W, Lynch J, Lynch P, Campbell A: Surveillance and management of patients at high genetic risk for ovarian carcinoma. Obstet Gynecol 59:589, 1982

38. Piver MS, Barlow JJ, Sawyer DM: Familial ovarian cancer: increasing in frequency? Obstet Gynecol 60:397, 1982

Athena - Preservation of the Ovary: A Reevaluation Copyright ©1984 Fertility and Sterility (Vol.42. No.4 October, 1984) Celso-Ramon Garcia, M.D. Winnifred B. Cutler, Ph.D. http://www.athenainstitute.com/sciencelinks/preserveovary.html
511 Fallopian tubes contain stem cells "Once harvested, the scientists were able to multiply and then coax the mesenchymal stem cells to turn into apparently healthy muscle, fat, cartilage and bone cell lines in the lab." BBC News - Page last updated at 23:08 GMT, Wednesday, 17 June 2009 00:08 UK - Stem Cell Research & Therapy - The utility of human fallopian tube mucosa as a novel source of multipotent stem cells for the treatment of autologous reproductive tract injury Jiaojiao Wang1, Yong Zhao1, Xiaoyun Wu2, Shande Yin1, Yunhai Chuai1 and Aiming Wang1* * Corresponding author: Aiming Wang one_army@sina.com Author Affiliations 1 Department for Gynaecology and Obstetrics, Navy General Hospital, PLA, Fuchengmen Road, No.6, Beijing 100048, China 2 Jing-Meng Stem Cell Technology CO., Ltd, Shangdi East Road,No.5-2, Beijing 100048, China http://www.stemcellres.com/content/6/1/98
512 Hysterectomies a source of stem cells Hysterectomies a stem cell source Stem cell research Stem cell work may find cures for intractable diseases Discarded fallopian tubes from hysterectomies could be a good source of donor stem cells, say researchers. http://news.bbc.co.uk/2/hi/health/8103345.stm
513 Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population. J Natl Cancer Inst. 2015 Jan 27;107(2). pii: dju410. doi: 10.1093/jnci/dju410. Print 2015 Feb. Ovarian cancer risk after salpingectomy: a nationwide population-based study. Falconer H1, Yin L2, Grönberg H2, Altman D2. http://www.ncbi.nlm.nih.gov/pubmed/25628372
514 In Germany (where hysterectomy rate is 60% that of the U.S. or 125,000 a year of the 41.2M women in Germany), doctors asked whether fallopian tubes should be removed during surgery and cautioned it could impact ovarian blood supply leading to the known issues with loss of ovarian function. Geburtshilfe Frauenheilkd. 2015 Apr; 75(4): 339–341. doi: 10.1055/s-0035-1545958 PMCID: PMC4437752 Should Fallopian Tubes Be Removed During Hysterectomy Procedures? – A Statement by AGO Ovar Sollen die Tuben im Rahmen der Hysterektomie entfernt werden? – Ein Statement der AGO Ovar M. Pölcher, S. Hauptmann, C. Fotopoulou, B. Schmalfeldt, I. Meinhold-Heerlein, A. Mustea, I. Runnebaum, J. Sehouli, and for the Kommission Ovar of the Gynecologic Oncology Study Group (AGO) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437752/
515 The truth about the number of medical malpractice claims vis a vis malpractice award caps. The number of meritorious claims that did not get paid was actually larger than the group of meritless claims that were paid. The findings appear in the May 11, 2006 issue of The New England Journal of Medicine. Press Releases 2006 Releases Study Casts Doubt on Claims That the Medical Malpractice System Is Plagued By Frivolous Lawsuits, Harvard School of Public Health, Todd Datz, May 10, 2006 http://archive.sph.harvard.edu/press-releases/2006-releases/press05102006.html
516 In an independent study of 31,000 cases, 1 out of every 25 patients had been harmed but only 4% of harmed patients had brought suit. Making Patient Safety the Centerpiece of Medical Liability Reform Hillary Rodham Clinton, and Barack Obama N Engl J Med 2006; 354:2205-2208May 25, 2006DOI: 10.1056/NEJMp068100 http://www.nejm.org/doi/full/10.1056/NEJMp068100
517 Exogenous E2 and cancer - estrogen metabolism may play a key role in estrogen-induced cancers because different estrogens differ in how they're broken down in the cell - As expected, when the carcinogenic 17beta-estradiol (E2) was used, nearly all hamsters with the pellets developed cancer within seven months. E2 promotes cell proliferation and produces oxygen radicals when metabolized by the cell. "That we found tumors in the EE plus menadione treated hamsters clearly suggests that estrogen receptor activity and oxidative stress are both needed for estrogen to produce cancer," Dr. Bhat says. InVivo - Columbia Univ. Health Sciences, Vol 2 No 10, May 26, 2003 - Estrogen-induced cancer 'Estrogen's role in cancer' http://www.cumc.columbia.edu/publications/in-vivo/Vol2_Iss10_may26_03/
518 No effect on ovarian function seen in short term after salpingectomy, but FSH markedly increases (FSH increase tied to Alzheimer's). Gynecology & Obstetrics Kamel et al., Gynecol Obstet 2012, 2:4 http://dx.doi.org/10.4172/2161-0932.1000124 Research Article Open Access Gynecol Obstet Volume 2 • Issue 4 • 1000124 ISSN:2161-0932 Gynecology an open access journal Ovarian Performance after Laparoscopic Salpingectomy or Proximal Tubal Division for Hydrosalpinx Ebtesam M Kamel* Faculty of medicine, Zagazig http://www.omicsonline.org/ovarian-performance-after-laparoscopic-salpingectomy-or-proximal-tubal-division-for-hydrosalpinx-2161-0932.1000124.pdf
519 The bilateral salpingectomy rates at a single institution increased from 3% in 2010 to 73% in the first 6 months of 2012 – a year after the center began offering the procedure to all women undergoing hysterectomy with ovarian preservation, Dr. Susan K. Park reported at the annual meeting of the American College of Obstetricians and Gynecologists. Dr. Susan Park "Across the board, patient acceptance of undergoing salpingectomy was very high," she said. Patients were counseled at a preoperative appointment that salpingectomy may reduce the risk of posthysterectomy pelvic adnexal masses and serous carcinomas. Only two women who were offered the procedure declined, said Dr. Park of Olive View–UCLA Medical Center, Los Angeles. American College of Surgeons: Routine bilateral salpingectomy with hysterectomy gains acceptance By: SHARON WORCESTER, ACS Surgery News Digital Network May 14, 2013 http://www.acssurgerynews.com/single-view/routine-bilateral-salpingectomy-with-hysterectomy-gains-acceptance/77f06cf6d393eab63dd7123c20613ec4.html
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RESULTS: All skin parameters in the hysterectomy group and the hysterectomy with BSO group worsened on weeks 24 and 48. Laxity/sagging and texture/dryness scores on weeks 24 and 48 were significantly worse in the BSO group; laxity/sagging and texture/dryness scores continued to worsen between 24 and 48 weeks. Scores for the Skindex-29 questionnaire emotion and symptom subscales were significantly higher in the BSO group compared with the non-BSO group.

CONCLUSIONS: Prophylactic BSO during hysterectomy is a significant independent risk factor for worsening skin laxity/sagging and texture/dryness in premenopausal women undergoing hysterectomy for benign conditions. Prophylactic BSO in the presence of dermatological conditions is also associated with reduced quality of life.

Potential adverse effects of prophylactic bilateral salpingo-oophorectomy on skin aging in premenopausal women undergoing hysterectomy for benign conditions.
Töz E, et al. Menopause. 2016. Authors Töz E1, Özcan A, Balsak D, Avc ME, Eraslan AG, Balc DD. Author information 11Department of Gynecology and Obstetrics, Izmir Tepecik Teaching and Research Hospital, Izmir, Turkey 2Department of Gynecology and Obstetrics, Istanbul Haliç University, Istanbul, Turkey 3Department of Gynecology and Obstetrics, Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey 4Department of Dermatology, Izmir Kent Hospital, Izmir, Turkey 5Department of Dermatology, Izmir Tepecik Teaching and Research Hospital, Izmir, Turkey. Citation Menopause. 2016 Feb;23(2):138-42. doi: 10.1097/GME.0000000000000511.
http://www.ncbi.nlm.nih.gov/m/pubmed/26382316/
531 Oophorectomy & Cushings symptoms - subclinical Cushings.