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

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

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

https://www.hormone.org/what-is-endocrinology/the-endocrine-system

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

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

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

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

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.

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

and

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

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

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.

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

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

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.

ACOG Practice Bulletin, 2008

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

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

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

"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.

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/23942250
and
http://www.medscape.com/ viewarticle/824027

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

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

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.

• 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.

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/

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."

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."

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."

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."

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

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

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

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.””

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.”

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

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.

“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

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

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

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

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

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

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.

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

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%;

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.

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

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

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."

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."

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

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

and

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

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."

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

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.

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."

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).

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

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

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

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

and

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

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.

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."

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)

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.

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)

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."

• • 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

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."

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:

(OBGYN Reform Note: This response is alarming and unmedical. Doctors should not presuppose that the ovaries are somehow vestigial organs just because they produce more androgens as women age than they do estrogens. This is because women's bodies are switching from the production of a steroid hormone that assists them with reproduction to one that makes the heart and other muscles stronger in order to support their health through the aging process. Alarming response.)

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

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.

In LH-responsive Cushing’s syndrome associated with bilateral adrenal hyperplasia, cortisol production is controlled via adrenal LH receptor expression. Luteinizing hormone. Cushing's Disease. Endogenous Cushing's Syndrome.

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