Abstract
Bilateral oophorectomy is used as a risk reduction strategy in BRCA1/2 mutation carriers, although data on long-term side effects are not yet available. In the general population, oophorectomy, particularly at a young age, has been associated with increased overall and cardiovascular disease (CVD) mortality. The mechanisms for this association are not well understood. We examined the association between prior bilateral oophorectomy, obesity, and all-cause, cancer, and CVD mortality. Our study population included women ages 40 and above from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative survey with enrollment from 1988 to 1994 and prospective mortality follow-up through December 31, 2006. We excluded women with a history of reproductive cancer or missing oophorectomy status, yielding a study population of 4,040. Cox proportional hazards modeling was used to estimate HR for all-cause and cause-specific mortality. In multivariate analyses, body mass index (BMI) significantly modified the association between oophorectomy and mortality (P(interaction) = 0.04). Women who were obese at the time of interview and who had an oophorectomy at less than 40 years were more than twice as likely to die [HR, 2.23; 95% confidence interval (CI), 1.25-3.98], particularly of CVD (HR, 2.77; 95% CI, 0.91-8.41), than nonobese women with intact ovaries. These associations persisted after excluding women who used estrogen therapy and women who had oophorectomy before 35 years of age. The joint effect of obesity and early oophorectomy on mortality was significantly greater than expected, given the independent effects of both exposures. Our results suggest that minimizing weight gain after oophorectomy and addressing cardiovascular risk factors could beneficially impact mortality.