Abstract PD09-01: Oophorectomy, Adiposity, and Mortality in NHANES III, a Nationally Representative Sample

Abstract

Abstract Background: Adiposity is a risk factor for many chronic diseases, including postmenopausal breast cancer. Oophorectomy is often performed to prevent ovarian cancer during elective hysterectomy. An estimated 300,000 oophorectomies are performed yearly in the U.S. Bilateral oophorectomy is also associated with reduced risk of breast cancer and is employed as a risk reduction strategy for women with BRCA 1/2 mutations. In the general population, oophorectomy has been associated with increased all-cause mortality and cardiovascular disease (CVD). We hypothesized that abrupt estrogen and androgen deprivation resulting from bilateral oophorectomy in premenopausal women may increase adiposity and thereby contribute to mortality. Methods: To test our hypothesis we evaluated the association between oophorectomy and adiposity (weight, BMI & waist circumference [WC]) cross-sectionally in NHANES III among women age 40 and older interviewed 1988-1994. We also evaluated the association between oophorectomy, BMI and all-cause, cancer, and CVD mortality through 2006. Women reporting bilateral oophorectomy or no oophorectomy with complete data on adiposity measures were included (N=3814). Survey weights were used in all analyses. Linear regression was used to calculate differences in mean adiposity, adjusting for demographic, behavioral and reproductive factors and BMI at age 25. Hazard Ratios (HRs) of all-cause, cancer, and CVD mortality were estimated using Cox regression. Cross-product terms were included in models to assess interaction and the Wald test was used to test statistical significance. Results: 20% of women reported a bilateral oophorectomy (N=530). Overall, there were no significant differences in adiposity between women reporting oophorectomy and those with intact ovaries after multivariate adjustment. However, women who had an oophorectomy before age 40 had significantly increased adiposity (Weight β=6.8 lbs p=0.009; BMI β=1.2kg/m2 p=0.009; WC β =3.4cm p=0.009). Results were similar after excluding estrogen users. Neither oophorectomy nor age at oophorectomy were independently associated with mortality, but the combined effect of prior bilateral oophorectomy and obesity was significantly associated with mortality. Women with BMI≥30 kg/m2 had 1.2 times the risk of all-cause mortality (HR=1.21 95% CI 1.03-1.42) and 1.4 times the risk of CVD mortality (HR=1.36 95% CI 1.00-1.86). Women who reported having a prior oophorectomy and had a BMI ≥30 kg/m2 had 1.7 times higher all-cause mortality (HR=1.65 95% CI 1.11-2.45, p-interaction=0.029) and 2.0 times higher CVD mortality (HR=1.97 95% CI 1.06-3.67, p-interaction=0.079) compared to women with intact ovaries who were not obese. Further, women with an oophorectomy <40 and BMI ≥30 kg/m2 had two fold increased all-cause mortality (HR=2.11 95% CI 1.00-4.48, p-interaction=0.047) and 3.8 fold increased CVD mortality (HR=3.77 95% CI 1.32-10.73, p-interaction 0.218). Significant interactions between oophorectomy and BMI were not observed for cancer mortality but the sample size was small. Conclusion: This study suggests that obesity is an important modifier of the association between oophorectomy and overall mortality. Future studies are needed to understand the temporality of these findings. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-01.