Women Undergoing Hysterectomy Before Age 65 Derive Survival Benefit From Ovarian Conservation

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Ovarian Cancer Survival

For women who are at average risk for ovarian cancer, conserving the ovaries during hysterectomy for benign disease benefits long-term survival until at least age 65, according to this study that used a Markov decision analytic model to determine the optimal strategy for maximizing survival in a hypothetical group of healthy women aged 40 to 80 years. Similar women were followed in the model from the age of surgery (40 or older) until age 80. The model simulated possible outcomes and estimated the benefits or risk of each of four treatment strategies: ovarian conservation with or without estrogen therapy, and bilateral oophorectomy with or without estrogen therapy. Five conditions were identified with reported risk related to the presence of postmenopausal ovaries or estrogen therapy - ovarian cancer, coronary heart disease, hip fracture, breast cancer, and stroke. Based upon a review of the English literature, the model considered the risk of mortality from these conditions after ovarian conservation versus oophorectomy. The outcome measured was the proportion of women who would be alive at age 80 years for each the four treatment strategies.

The model determined that ovarian conservation until at least age 65 benefits long-term survival in women with benign disease: women with oophorectomy before age 55 have 8.5% excess mortality by age 80 compared with those in whom ovaries are spared. Women with oophorectomy before age 59 have 3.92% excess mortality; by age 75, excess mortality for oophorectomy is less than 1%. For women at average risk of ovarian cancer, coronary heart disease, osteoporosis, breast cancer, and stroke, the probability of surviving to age 80 after hysterectomy at ages 50 to 54 varies from 62.46% for ovarian conservation without estrogen therapy to 53.88% for oophorectomy without estrogen therapy, according to the model. Reductions in death from coronary heart disease and hip fracture for those in whom ovaries were conserved far outweighed the number who would have died from ovarian cancer.

According to the authors, oophorectomy is routinely recommended for women undergoing hysterectomy to reduce the risk of ovarian cancer. But after menopause, the ovaries continue to produce significant amounts of testosterone and androstenedione, which are converted to estrogen peripherally. Although younger women with BRCA1 or BRCA2 mutations who have significant risk for breast or ovarian cancer may derive a survival benefit from oophorectomy, women at average risk for these cancers experience increased risk of osteoporotic fracture and coronary heart disease. The study found that women younger than age 65 clearly benefit from ovarian conservation, and at no age is there a clear benefit from oophorectomy.

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Comment. This study was designed to provide guidance regarding the choice of including a concomitant bilateral oophorectomy at the time of hysterectomy, for clinicians who perform hysterectomy and for women who are about to undergo hysterectomy. For years, prophylactic oophorectomy has been routinely recommended to women older than 40 years of age in order to prevent the future occurrence of ovarian cancer. The rationale was that ovarian cancer is often a silent disease, generally coming to clinical attention at a late stage associated with a poor prognosis of survival, and that highly sensitive means of screening and improved therapies do not yet exist for ovarian cancer. This dogma, which results in an estimated 300,000 prophylactic bilateral oophorectomies each year, is now called into question.

This study utilized a Markov decision analytic model, a technique that simulates large hypothetical groups of patients that are followed through the model over time. By recreating possible outcomes for these hypothetical patients, the benefits or risks for each treatment strategy may be estimated. The endpoint studied in this particular model was maximal survival.

The important finding from this analysis is that ovarian preservation was associated with a lower mortality at all ages from 40 to 80. The increased risk of coronary heart disease (CHD) after oophorectomy was an important driver of the final results; however, even when the model assumed no harmful effects of oophorectomy on subsequent occurrence of CHD, an advantage of ovarian preservation on mortality was still observed. A limitation of decision analysis is that the results are derived solely from risk estimates that are incorporated into the model; thus, the final analysis is only as reliable as the risk estimates available. In this study, the probability estimates were obtained mostly from case-control studies with potential for bias and incomplete information. Much of the data used to establish the risk estimates was derived from studies of predominantly white women, another limitation, since a substantial number of hysterectomies are performed on nonwhite women, and the probability estimates utilized need to be verified for these other groups of women. In addition, other important endpoints such as quality of life, cancer phobia, persistent pelvic pain, and need for reoperation for adnexal pathology were not included in this model, as few data exist regarding these outcomes or the contribution of these variables to mortality was estimated to be negligible by the investigators.

The importance of this study is the demonstration that ovarian conservation at the time of hysterectomy (in women who are not at increased risk for ovarian cancer) may lead to longer survival, making ovarian conservation a viable option rather than an extreme measure, even in the postmenopausal woman. Clearly, the decision for oophorectomy or ovarian conservation should balance risks specific to the patient as well as potential benefits and patient preferences. Certainly, there are still women who will benefit from concomitant oophorectomy at the time of hysterectomy, notably, those with intractable endometriosis. However, for most women, the scales are now tipping towards ovarian conservation.

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