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    Bilateral oophorectomy: Solving the risk/benefit equation — Choosing candidates, monitoring outcomes

    Prophylactic bilateral oophorectomy at the time of hysterectomy confers long-term benefits for many women.

    Bilateral oophorectomy at the time of hysterectomy for benign disease has been commonly recommended to women over the age of 40 or 45 years to prevent the development of ovarian cancer. In the United States, at least 300,000 women annually have bilateral oophorectomy at the time of hysterectomy: approximately 54% of all hysterectomy procedures.1 Concomitant bilateral oophorectomy is most often performed in women 50 to 54 years of age. In this group, 78% of hysterectomies include bilateral oophorectomy.1

    However, prophylactic surgery should be performed only if there is evidence that it clearly benefits the patient.2 Recent evidence suggests that there may be long-term health benefits and longer survival for women who choose ovarian conservation at the time of hysterectomy for benign disease. In addition, oophorectomy improves quality of life and provides a survival benefit for other women.3

    Ovarian cancer prevention in women at increased risk

    Although the lifetime risk of ovarian cancer is 1.4% overall among US women, the risk varies by subgroup. For example, white women at age 65 who have had 3 or more term pregnancies and at least 4 years of combined oral contraceptive (OC) use have a risk of 0.3%, whereas nulliparous women with the same OC use have a risk of 1.6%.4 Moreover, some women have mutations in the BRCA1 or BRCA2 gene, and such mutations may disrupt DNA repair mechanisms, predisposing these women to oncogenesis in the ovary and breast.5 It appears at present that no more than 10% of epithelial ovarian cancers are due to inherited mutations in ovarian cancer-related genes.6,7 Nevertheless, the lifetime risk of ovarian cancer among women with these mutations is very high: for women with BRCA1 mutations the risk is 36% to 46%, and for BRCA2 mutations the risk is 10% to 27%.8 In addition, women with the hereditary nonpolyposis colorectal cancer mutation have a 12% lifetime risk of ovarian cancer.9

    For women with BRCA1 and BRCA2 mutations, annual screening for ovarian cancer using transvaginal ultrasound and the CA125 blood test has not proven effective for detecting disease early enough to influence survival, and is not recommended.10 The only intervention shown to be effective in reducing the incidence of ovarian cancer in women carrying the BRCA1 or BRCA2 gene mutation is bilateral salpingo-oophorectomy.11 As a result, authorities agree that women who have known genetic mutations that increase the risk of ovarian and breast cancers should strongly consider oophorectomy after completion of childbearing.12

    About 2% of women have a family history consistent with an increased risk of ovarian or breast cancer. Recent studies suggest that a large number of low-penetrance genetic variants account for instances of women who have a strong family history but do not have BRCA1 or BRCA2 mutations.13 Genetic counseling from a trained healthcare provider can help these women make informed decisions about the advisability of oophorectomy. Removal of the fallopian tubes and ovaries in women with the BRCA1 or BRCA2 gene mutation reduces the risk of ovarian cancer by 80%.14 Further, a large retrospective study noted a decreased risk of breast cancer during follow-up after unilateral oophorectomy alone or bilateral oophorectomy performed with or without hysterectomy, particularly when these procedures were done before age 45 years (ratio of observed to expected cases ranging from 0.65 to 0.89).15 Both fallopian tubes also should be removed at surgery because recent evidence has shown that most BRCA-related ovarian cancers are actually of tubal origin, beginning in the epithelial cells of the fimbria of the fallopian tube.16 This finding also explains why ultrasound is not effective for cancer screening.

    Additionally, some women without a family or personal history that increases their risk of ovarian cancer may wish to have their ovaries removed because of concerns about the possibility of developing ovarian cancer. If one of these women wishes to proceed with oophorectomy after a full discussion of her specific risk for ovarian and breast cancers and the risks and benefits of the surgery, I would certainly respect her wishes.

    Risks and side effects of oophorectomy

    Oophorectomy appears to be associated with long-term health risks. In premenopausal women, oophorectomy immediately reduces blood levels of ovarian estrogens and androgens. Even after menopause, the ovaries continue to produce significant amounts of testosterone and androstenedione, which undergo peripheral conversion to estrone by skin, muscle, and fat cells.17,18

    Evidence indicates that endogenous estrogens are beneficial to the cardiovascular system and for long-term health and neurologic function.19-22 This is a crucial consideration because although ovarian cancer causes approximately 15,000 deaths per year in the US, coronary heart disease (CHD) accounts for 327,000 deaths per year,20 and dementia attributable to bilateral oophorectomy may affect between 100,000 and 200,000 US women.21 For example, a Danish cohort study found 7 times the risk of ischemic heart disease in women with a history of oophorectomy before age 40 years compared with women having oophorectomy after age 45 years. The risk of heart disease increased with younger age at oophorectomy.22

    With regard to neurologic function, a cohort study of premenopausal women undergoing unilateral or bilateral oophorectomy found that cognitive impairment or dementia occurred in 76 of 813 women (9.3%), representing nearly a 50% increase in risk.23

    Data from the Nurses' Health Study corroborate these findings. During 24 years of follow-up, oophorectomy was associated with increased risks of death from CHD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.00-1.64) and death from all causes (HR, 1.12; 95% CI, 1.03-1.21).20 Among women who had never used estrogen therapy, bilateral oophorectomy before 50 years of age was associated with increased risks of all-cause mortality, CHD, and stroke. Given that the life expectancy after surgery is 35 years, 1 additional death would be expected for every 9 oophorectomies performed before age 50. After oophorectomy, women had a markedly reduced risk of ovarian cancer; however, they had higher risks of lung cancer (HR, 1.31; 95% CI, 1.02-1.68) and total cancer mortality (HR, 1.17; 95% CI, 1.04-1.32). Oophorectomy was not associated with increased survival in any analysis or age group. In addition to its effects on CHD risk and cognitive impairment or dementia, bilateral oophorectomy before the onset of menopause has been shown to increase the risks of Parkinson disease and anxiety or depression.23-25 Younger age at oophorectomy increased the risks for these neurologic conditions.

    Although a recent analysis of the Women's Health Initiative (WHI) found that bilateral oophorectomy might not increase the risks of cardiovascular disease, cancer, or overall mortality when compared with ovarian conservation, this study had a short follow-up (mean, 7.6 years).26 Because 20% of myocardial infarctions occur before age 65 and women were an average age of 63 years when the WHI enrollment began, some selection bias cannot be ruled out. In addition, the premenopausal operations were self-reported, which means that the data may be affected by recall bias.

    A review of prophylactic oophorectomy by the Society of Gynecologic Oncologists Clinical Practice Committee suggested that ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurologic disease.27 The decision to perform concurrent bilateral salpingo-oophorectomy in women at average risk of ovarian cancer therefore should include a consideration of individual risk factors, such as family history of cardiovascular and neurologic disease, OC use, parity, and other epidemiologic factors.28 Careful preoperative counseling is required, and the decision should be individualized.

    Estrogens and androgens inhibit bone resorption, and androgens stimulate bone formation.29 Both premenopausal and postmenopausal women who undergo bilateral oophorectomy have an increased risk of osteoporosis because of the reduction in hormone levels. Postmenopausal women who underwent oophorectomy at a median age of 62 years had 54% more osteoporotic fractures than those with intact ovaries.30 However, 2 other studies found no association of oophor-ectomy with bone loss or fracture risk.31,32

    About 90% of premenopausal women have vasomotor symptoms after oophorectomy,33 and many women also experience mood changes, a decline in feelings of well- being, decreased sexual desire, sleep disturbances, and headaches.34-36 Over time, vaginal dryness, painful intercourse, bladder dysfunction, and symptoms of depression may occur.36-38 Although estrogen therapy may reduce some of the increased risks and symptoms that occur after oophorectomy, continuation rates of estrogen therapy are low and new hormone prescriptions have decreased significantly over the past decade.39 Likewise, continuation rates for bisphosphonates or statins as specific therapy for osteoporosis or heart disease are less than 25% after 1 year.40,41 Critics suggest that medical therapy can ameliorate all the medical conditions caused by oophorectomy, but this argument is not valid because of the poor continuation rates of these medications. Therefore, medical treatment for conditions related to estrogen deficiency after oophorectomy is not likely to be effective for most women.

    Ovarian cancer prevention for women at average risk

    Theoretically, there may be an age at which the benefits of oophorectomy to prevent ovarian cancer outweigh the possibility of increased risks of CHD, neurologic conditions, and overall mortality in low-risk women. The incidence of ovarian cancer increases with age, peaking at approximately 75 years. It is likely that with advancing age, the influence of ovarian hormones decreases compared with that of other known risk factors for heart disease and other causes of mortality. A computer modeling study examined risk data among women with and without oophorectomy and found that ovarian conservation until at least age 65 years improved long-term survival for women who had an average risk of ovarian cancer.42 However, no study has determined the age at which oophorectomy should be recommended. Endogenous bioavailable testosterone and estrogen in postmenopausal women are partly protective against the loss of muscle strength that predisposes these women to falls and against the continuing loss of bone mineral density that increases the risk of fractures.43 Therefore, even in older women, these ovarian hormones may have benefit.

    Other strategies may be taken to decrease the risk of ovarian cancer, including the use of OC pills or tubal ligation. Taking OCs for 5 or more years decreases the risk of ovarian cancer by 50%,28 and tubal ligation decreases the risk by 34%.44 Hysterectomy alone decreases the risk of ovarian cancer by 33%.45

    Oophorectomy and breast cancer

    A case-control study showed that oophorectomy reduced the risk of breast cancer by 56% for BRCA1 and 46% for BRCA2 carriers.46 Risk reduction was even greater for women younger than 40 years at surgery, and the protective effect persisted 15 years after surgery. A study of a general Swedish population showed a 50% reduction in the risk of breast cancer among women who had bilateral oophorectomy before age 50 years, and this effect was evident within 10 years of the surgery.47

    Oophorectomy may be recommended as treatment for some women with breast cancer. Although tamoxifen and aromatase inhibitors are typically used to prevent recurrences of breast cancer in postmenopausal women with estrogen-receptor-positive, early stage tumors, some investigators recommend oophorectomy combined with tamoxifen therapy. This combination treatment was associated with higher 10-year disease-free survival than was reported for women treated with tamoxifen alone.48

    In addition, oophorectomy has been used as treatment for premenopausal women with metastatic breast cancer, achieving response rates of 14% to 70%, depending on the study.49 Patients with breast cancer in clinical remission who are undergoing a hysterectomy for benign disease may consider concurrent oophorectomy because it has been associated with a reduction in the risk of relapse.50

    Oophorectomy and endometriosis

    Among women with severe, symptomatic endometriosis unresponsive to conservative management, bilateral oophorectomy concurrent with hysterectomy decreased the risks of recurrent or persistent symptoms and the need for reoperation.51 One study of women with symptomatic endometriosis compared outcomes between women who had a hysterectomy with ovarian conservation and women who had a hysterectomy with concurrent bilateral oophorectomy.52 Of the 29 women with ovarian conservation, 18 (62%) had recurrent pain and 9 (31%) required reoperation. Of the 109 women who had both ovaries removed, 11 (10%) had recurrent pain and 4 (4%) required reoperation. Women who underwent hysterectomy with ovarian conservation had 6 times the risk of developing recurrent pain and 8 times the risk of reoperation compared with women who had concurrent bilateral oophorectomy.

    Another study of confirmed endometriosis found that of the 47 women who had a hysterectomy with ovarian conservation, 9 (19%) required further surgery.53 The 2-, 5-, and 7-year reoperation rates were 4%, 13%, and 23%, respectively. Of the 50 women who had a hysterectomy with bilateral oophorectomy, only 4 (8%) required reoperation, with reoperation rates of 4% at 2 years, 8% at 5 years, and 8% at 7 years. Preservation of both ovaries doubled the risk of reoperation regardless of the patient's age. The authors concluded that local excision of endometriosis is associated with good short-term outcomes but has a high reoperation rate, whereas hysterectomy with bilateral salpingo-oophorectomy has a low reoperation rate.

    In contrast, an analysis of women younger than 40 years with advanced endometriosis found that the time to repeat surgery was the same whether the ovaries were removed or conserved. Given the problems associated with early menopause, the authors recommended that for women younger than 40 years of age, hysterectomy with ovarian conservation should be considered.53

    Avoiding future adnexal surgery

    The percentage of women who require reoperation after hysterectomy with ovarian conservation is low, with residual ovary syndrome occurring at a rate of approximately 2.8%.54 Asymptomatic cystic ovarian tumors are relatively prevalent (6.6%) in postmenopausal women.55 These cysts do not undergo transformation to cancer, however, and in most cases do not need to be removed. Another study reported that only 0.75% of women developed ovarian cancer after hysterectomy and ovarian conservation performed by the vaginal or abdominal route.56 Performing oophorectomy to avoid future surgery appears unfounded.


    Medical decisions involve a balance of benefits and risks for each individual patient. Prophylactic surgery should be performed only if the weight of the evidence establishes that it clearly benefits the patient. Undoubtedly, bilateral salpingo-oophorectomy is advisable for women who have a high risk of ovarian and breast cancer because of gene mutations. In addition, women older than 40 years with severe endometriosis unresponsive to conservative treatment may benefit from oophorectomy.

    The decision about oophorectomy for other women is problematic, and more research will be needed to answer the remaining clinical questions. Unfortunately, the entire body of evidence that examines the risks and benefits of bilateral salpingo-oophorectomy is derived from observational studies, which have significant inherent limitations. At a minimum, gynecologists should provide detailed informed consent covering the risks and benefits of both oophorectomy and ovarian conservation.

    DR PARKER is on the adjunct faculty of the John Wayne Cancer Institute at St John's Health Center and in private practice in Santa Monica, California. He reports no real or apparent conflicts of interest with respect to the content of this article.


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    William H. Parker, MD
    DR. PARKER is a Clinical Professor at the UCLA School of Medicine, Los Angeles, Calif., and Chair of the Department of Obstetrics and ...


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