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

9/26/2016 1

Risks of Bilateral Oophorectomy‐ Symptoms, Disease, and Mortality

Philip M. Sarrel, M.D. Emeritus Professor of Obstetrics, Gynecology and Psychiatry Yale University

Disclosure

• Philip Sarrel, M.D. is the Founder and

President of The Advancing Health After Hysterectomy Foundation, Inc. (a non‐profit corporation registered in Connecticut)

• The Foundation does not receive funding from

the pharmaceutical industry 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.

• 1. Mikhail E. AJOG, 2015;213:713‐721.

Oophorectomy: 1998‐2011

• Mikhail E AJOG, 2015;213:713‐721.

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The Age at which women undergo Hysterectomy

Overall BSO Age n (%) n (%) 18‐24 23,722 (0.4) 4079 (17.2) 25‐34 577,636 (9.6) 111,548 (19.3) 35‐44 2,382,001 (39.7) 699,080 (29.4) 45‐54 2,146,887 (35.8) 1,310,043 (61.0) 55‐64 459,338 (7.7) 301,061 (65.5) >65 409,733 (6.8) 195,661 (47.8)

Mikhail E AJOG, 2015;213:713‐721. (NIS, 1998‐2011). 1.0 million women age 45 and under had their ovaries removed between 1998‐2011

BSO : Adverse Effects

• The major concern about women whose
• varies are removed before age 45 is that the

benefits of BSO are outweighed by increased frequency and severity of symptoms, and increase in disease risk and mortality rates. For this reason, ACOG has advocated ovarian conservation and bilateral salpingectomy (BS) in these women1

• 1. Elective and risk reducing salpingo‐oophorectomy. ACOG Practice Bulletin No. 89.Obstet

Gynecol 2008;111:231‐41.

Symptoms Are More Frequent and Severe After Surgical Menopause

• Hot flashes1,2,5
• Fatigue1,2,5
• Cardiac symptoms2,3
• Depressed affect2‐4

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 5. Challberg J, et al. Menopausal symptoms and bone health after risk reducing BSO Br J Ca 2011;105(1):22‐27

Symptoms Due to Ovarian Hormone Insufficiency Are More Severe After Hysterectomy/BSO

Oldenhave1 reported 90% vs 50% with severe hot flashes comparing surgical vs. natural menopause Kronenberg2 reported findings from more than 900 women comparing natural and surgical menopause: – 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 Rosenberg3 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. 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

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Disease and Mortality After Surgical Menopause: A 75‐Year Saga1,2

• 1. Albright F, Smith DH, Richardson AM. Postmenopausal osteoporosis. JAMA 1941;116:2465
• 2. Ackerman RF, et al. Various factors and the degree of coronary atherosclerosis in women.

Circulation 1950;1345

Increase in Disease Associated With Surgical Menopause

• Osteoporosis 5,6
• Hysterectomy w/ or w/o oophorectomy increases
• steoporosis risk
• Cardiovascular disease/myocardial infarction1‐4
• Hypertension and Stroke1,2
• Dementia and Alzheimer’s Disease7
• 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.
• 6. Yoshida T, et al. Impact of surgical menopause on lipid and bone metabolism. Climacteric 2011;14:445‐452.
• 7. 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.

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

• steoporosis compared to 3% who received estrogen therapy1
• 1. Challberg J, et al Br J Ca 2011;105(1):22‐27

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Percentage of Oophorectomized Women With Coronary Sclerosis: Grade 3 or Greater

100 80 60 40 20 30‐39 40‐49 50‐59 60‐69 70‐79 80‐89

Percent

Men controls Bilateral oophorectomized women

Age (y)

Wuest J, et al. Circulation. 1953;7:801‐809. Women controls

BSO, Hot Flashes and Hypertension

Increased sympathetic tone with hot flashes1‐5

• 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

Surgical menopause at age 45 or younger without hormone replacement shows increased risks for: (Mayo Clinic Oophorectomy Study)1

• Osteoporosis and bone fx

50 %

• Coronary Heart Disease

33 %

• Stroke

62 %

• Cognitive impairment

60 % All‐cause mortality: 28 %

• 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.

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ET and HT Reduce Mortality After Surgical Menopause

Rivera CM, et al. Increased cardiovascular mortality after bilateral oophorectomy. Menopause 2009;16:15‐23 :

• BSO <45 not treated with ET

HR= 1.67

• BSO <45 treated with ET

HR = 0.65

HT‐Cochrane Database Syst Rev. 2015 : reduction = 39% (Women under 60 or < 10 yrs post menopause) Savolainen‐Peltonen. JCEM 2016;101:2794‐2801 : “The sooner after the onset of menopause an estradiol‐based HT is initiated, the better it protects against cardiac death risk. ET reduction = 47%”

WHI 2011: Clinical Outcomes HR by Age Groups: CEE vs. Placebo

Age 50‐59 60‐69 70‐79 CHD 0.60 1.00 1.06 Total M.I. 0.54 1.05 1.23 Stroke 1.09 1.27 1.13 DVT 0.71 1.20 1.26 PE 1.20 1.57 0.74 Inv Breast Ca 0.80 0.73 0.81 Colorectal Ca 0.80 0.90 1.83 Hip fx 1.55 0.87 0.90 DEATH 0.73 1.04 1.12 La Croix A et al. JAMA 2011; 305: pg. 1311 BSO= 39%. Hyst <age40= 40%; age 40‐49= 44%. In age 50‐59 Xs mortality =13/10,000/yr

BSO (Cont.)

• In women age 45 and younger,

estrogen therapy controls symptoms and reduces disease risk and mortality when it is initiated close to the time of BSO, continued at least until the average age of natural menopause, and is prescribed at higher doses than usual.

Hormone replacement in young women with surgical ovarian insufficiency

• Women with oophorectomy at age 45 or younger need higher

dose estrogen replacement therapy1

• Treatment should be at least until age of natural menopause
• Best results are seen in women who start at time of
• ophorectomy and continue for 10 years or longer
• Progesterone in women with retained uterus
• 1. Popat VB, et al. Fertil Steril 2008;89:429‐433; JCEM 2014;99(9):3418‐26

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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.