Most BSOs are done at the time of hysterectomy and most occur before - PDF document

9/26/2016 Disclosure • Philip Sarrel, M.D. is the Founder and President of The Advancing Health After Risks of Bilateral Oophorectomy ‐ Hysterectomy Foundation, Inc. (a non ‐ profit Symptoms, Disease, and Mortality corporation registered in Connecticut) • The Foundation does not receive funding from Philip M. Sarrel, M.D. the pharmaceutical industry Emeritus Professor of Obstetrics, Gynecology and Psychiatry Yale University Oophorectomy: 1998 ‐ 2011 Bilateral Salpingo ‐ Oophorectomy (BSO) • Most BSOs are done at the time of hysterectomy and most occur before age 50. 1 There are more than 1 million women who have undergone BSO at age 45 or younger. • Mikhail E AJOG, 2015;213:713 ‐ 721. 1. Mikhail E. AJOG, 2015;213:713 ‐ 721. 1

9/26/2016 The Age at which women undergo Hysterectomy BSO : Adverse Effects Overall BSO Age n (%) n (%) • The major concern about women whose ovaries are removed before age 45 is that the 18 ‐ 24 23,722 (0.4) 4079 (17.2) benefits of BSO are outweighed by increased 25 ‐ 34 577,636 (9.6) 111,548 (19.3) frequency and severity of symptoms, and increase in disease risk and mortality rates. 35 ‐ 44 2,382,001 (39.7) 699,080 (29.4) For this reason, ACOG has advocated ovarian conservation and bilateral salpingectomy (BS) 45 ‐ 54 2,146,887 (35.8) 1,310,043 (61.0) in these women 1 55 ‐ 64 459,338 (7.7) 301,061 (65.5) >65 409,733 (6.8) 195,661 (47.8) 1.0 million women age 45 and under had their ovaries removed between 1998 ‐ 2011 1. Elective and risk reducing salpingo ‐ oophorectomy. ACOG Practice Bulletin No. 89.Obstet Mikhail E AJOG, 2015;213:713 ‐ 721. (NIS, 1998 ‐ 2011). Gynecol 2008;111:231 ‐ 41. Symptoms Are More Frequent and Severe Symptoms Due to Ovarian Hormone Insufficiency Are After Surgical Menopause More Severe After Hysterectomy/BSO • Hot flashes 1,2,5 Oldenhave 1 reported 90% vs 50% with severe hot flashes comparing surgical vs. natural menopause • Fatigue 1,2,5 • Cardiac symptoms 2,3 Kronenberg 2 reported findings from more than 900 women comparing natural and surgical menopause: • Depressed affect 2 ‐ 4 – The incidence of chest pressure and change in heart rate is doubled in women with surgical menopause (22% ‐ 47%) – Depression with suicidal thoughts are also doubled (10%) 2 Rosenberg 3 reported hospitalization for suicide attempt was more than doubled in women who had BSO at age 35 and younger. 1. Oldenhave A. Impact of climacteric on well ‐ being. Am J Obst Gynecol 1993; 168:772 ‐ 80 2. Kronenberg F Hot flashes, Epidemiology and physiology Ann N Y Acad Sci.1990;592:52 ‐ 86 3. Rosenberg G et al. Early menopause and the risk of myocardial infarction. AJOG 1981;139:47 ‐ 51 4. Cohen LS, et al. Risk for new onset depression during menopausal transition. Arch Gen Psych. 2006;63:385 ‐‐ 90 1. Oldenhave A. Impact of climacteric on well ‐ being. Am J Obst Gynecol 1993; 168:772 ‐ 80 5. Challberg J, et al. Menopausal symptoms and bone health after risk reducing BSO Br J Ca 2011;105(1):22 ‐ 27 2. Kronenberg F. Ann N Y Acad Sci . 1990;592:52-86. 3. Rosenberg G et al. Early menopause and the risk of myocardial infarction. AJOG 1981;139:47 ‐ 51 2

9/26/2016 Increase in Disease Associated With Surgical Menopause Osteoporosis 5,6 • • Hysterectomy w/ or w/o oophorectomy increases osteoporosis risk Disease and Mortality After Surgical Cardiovascular disease/myocardial infarction 1 ‐ 4 • Menopause: A 75 ‐ Year Saga 1,2 Hypertension and Stroke 1,2 • Dementia and Alzheimer’s Disease 7 • 1. Rossouw JE, Prentice RL, et al. HT and CVD by age and yrs. since menopause. JAMA 2007;297:1465 ‐ 77 2. Gast GC, Grobee DE,et al. Menopausal complaints associate with CVD risk. Hypertension 2008;51:1492 ‐ 8 3. Silveira JS, et al. Hot flashes: emerging cv risk factors…Menopause 2016;23:846 ‐ 855 4. Franco OH, et al. Vasomotor symptoms…cvd risk…meta ‐ analysis. Maturitas 2015;83:353 ‐ 361 5. Lindsay R. Sex steroids and osteoporosis. Clin Obstet Gynecol 1987;30(4):847 ‐ 859. 1. Albright F, Smith DH, Richardson AM. Postmenopausal osteoporosis. JAMA 1941;116:2465 6. Yoshida T, et al. Impact of surgical menopause on lipid and bone metabolism. Climacteric 2011;14:445 ‐ 452. 2. Ackerman RF, et al. Various factors and the degree of coronary atherosclerosis in women. 7. Faubion SS, Kuhle CL,et al. long ‐ term health consequences of premature menopause or early Circulation 1950;1345 Menopause and considerations for management. Climacteric 2015;18:483 ‐ 491. Oophorectomy and Osteoporosis Bone density after >24 months estrogen therapy vs deprivation: T score < ‐ 1.0 (osteopenia or osteoporosis): 16% vs 47% of those with > 24 mos deprivation (p=0.03); By age 50, 13% with >24 mos of deprivation prior to age 50 had osteoporosis compared to 3% who received estrogen therapy 1 1. Challberg J, et al Br J Ca 2011;105(1):22 ‐ 27 3

9/26/2016 Percentage of Oophorectomized Women With Coronary Sclerosis: Grade 3 or Greater 100 Bilateral oophorectomized women 80 Women controls 60 Percent Men controls 40 20 0 30 ‐ 39 40 ‐ 49 50 ‐ 59 60 ‐ 69 70 ‐ 79 80 ‐ 89 Age (y) Wuest J, et al. Circulation. 1953;7:801 ‐ 809. BSO, Hot Flashes and Hypertension Surgical menopause at age 45 or younger without hormone replacement shows increased risks for: (Mayo Clinic Oophorectomy Study) 1 Increased sympathetic tone with hot flashes 1 ‐ 5 • Osteoporosis and bone fx 50 % • Coronary Heart Disease 33 % • Stroke 62 % • Cognitive impairment 60 % All ‐ cause mortality: 28 % 1. Kronenberg F. Hot flashes, Epidemiology and physiology Ann N Y Acad Sci.1990;592:52 ‐ 86 2. Rossouw JE, Prentice RL, et al. HT and CVD by age and yrs. since menopause. JAMA 2007 3. Gast GC, Grobee DE, et al. Menopausal complaints associate with CVD risk. Hypertension 2008 4. Silveira JS, et al. Hot flashes: emerging cv risk factors…Menopause 2016;23:846 ‐ 855 5. Franco OH, et al. Vasomotor symptoms…cvd risk…meta ‐ analysis. Maturitas 2015;83:353 ‐ 361 1. Faubion SS, Kuhle CL,et al. long ‐ term health consequences of premature menopause or early Menopause and considerations for management. Climacteric 2015;18:483 ‐ 491. 4

9/26/2016 ET and HT Reduce Mortality After WHI 2011: Clinical Outcomes HR by Age Surgical Menopause Groups: CEE vs. Placebo Age 50 ‐ 59 60 ‐ 69 70 ‐ 79 Rivera CM, et al. Increased cardiovascular mortality after bilateral oophorectomy. CHD 0.60 1.00 1.06 Menopause 2009;16:15 ‐ 23 : Total M.I. 0.54 1.05 1.23 • BSO <45 not treated with ET HR= 1.67 Stroke 1.09 1.27 1.13 DVT 0.71 1.20 1.26 • BSO <45 treated with ET HR = 0.65 PE 1.20 1.57 0.74 Inv Breast Ca 0.80 0.73 0.81 Colorectal Ca 0.80 0.90 1.83 HT ‐ Cochrane Database Syst Rev. 2015 : reduction = 39% (Women under 60 or < 10 yrs post menopause) Hip fx 1.55 0.87 0.90 DEATH 0.73 1.04 1.12 Savolainen ‐ Peltonen. JCEM 2016;101:2794 ‐ 2801 : “The sooner after the onset of BSO= 39%. Hyst <age40= 40%; age 40 ‐ 49= 44%. In age 50 ‐ 59 Xs mortality =13/10,000/yr menopause an estradiol ‐ based HT is initiated, the better it protects against cardiac death risk. ET reduction = 47%” La Croix A et al. JAMA 2011; 305: pg. 1311 Hormone replacement in young women with BSO (Cont.) surgical ovarian insufficiency • In women age 45 and younger, • Women with oophorectomy at age 45 or younger need higher estrogen therapy controls symptoms dose estrogen replacement therapy 1 and reduces disease risk and mortality when it is initiated close to the time of • Treatment should be at least until age of natural menopause BSO, continued at least until the average age of natural menopause, • Best results are seen in women who start at time of oophorectomy and continue for 10 years or longer and is prescribed at higher doses than usual. • Progesterone in women with retained uterus 1. Popat VB, et al. Fertil Steril 2008;89:429 ‐ 433; JCEM 2014;99(9):3418 ‐ 26 5

9/26/2016 Oophorectomy: Key Points • Despite ACOG recommendations to conserve ovaries at the time of hysterectomy, BSO continues to be the major cause of estrogen deficiency in premenopausal women The steep decline in estrogen use after surgical menopause has resulted in more than a • million younger women who are at increased risk for osteoporosis, atherosclerosis, dementia, sexual dysfunction and other conditions due to estrogen deficiency • Although the WHI ‐ estrogen Study findings only apply tangentially to these women, major cohort studies indicate the disease and mortality consequences of estrogen deficiency can be overcome by estrogen therapy initiated as close as possible to the time of surgery and continued for 10 years or more (at least until the age of natural menopause) • A major public health education campaign is called for to help women and health care providers understand the risks of not using estrogen after BSO and the benefits and safety of its use. 6