Bilateral Oophorectomy, Body Mass Index, and Mortality in U.S. Women Aged 40 Years and Older

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 (Pinteraction = 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.

Weight Gain After Oophorectomy Among Women with a BRCA1 or BRCA2 Mutation

“…A few studies have illustrated that oophorectomy is associated with metabolic syndrome, which is described as the clustering of abdominal obesity, dyslipidemia, hypertension and hyperglycemia, compared with women with intact ovaries [24][25][26]. Of relevance is a large study using NHANES III data from women aged 40 years or older (n = 4040), no significant increase in all-cause mortality with oophorectomy prior to age 40 years; however, they found that women who were obese at the time of oophorectomy had a twofold increased risk of cardiovascular disease mortality [27]. These findings suggest that overweight women undergoing early oophorectomy should be monitored for cardiovascular disease risk factors as well as for bodyweight.…”

Long-term overall and disease-specific mortality associated with benign gynecologic surgery performed at different ages

“…7 Similarly, another study linked oophorectomy to increased mortality, primarily due to cardiovascular disease, among obese women who underwent surgery before age 40 and did not use menopausal hormone therapy (HT). 8 Finally, one investigation found that BSO was unrelated to mortality. 9 Thus, data suggest that incidental BSO may be associated with increased mortality, but clarification of risks, particularly in relation to age at surgery are needed.…”

Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy

“…This diagnosis could explain the more frequent family history of MI in women who had BSO before age 45 years in the current study since PCOS patients are insulin resistant, and their family members are more often insulin resistant and prone to MI [30][31][32]. In a previous study also using the NHANES database [33], women who were obese at the time of the interview, a common finding in PCOS women, and who had BSO before age 40 years, were more than twice as likely to die, particularly of CVD, than non-obese women with intact ovaries. The inclusion of women with PCOS could also possibly explain the higher risk for coronary heart disease among women younger than age 45 at the time of hysterectomy with BSO in the Nurse's Health Study [3], and the higher prevalence of diabetes and hypertension among younger women with BSO in the California Teachers Study [25].…”