Androgens, Bilateral Oophorectomy, and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures

OBJECTIVE: Diabetes elevates cardiovascular disease (CVD) risk more markedly in women than in men. Because the high risk of CVD among women with type 2 diabetes (DM2) may be partly due to increased ovarian androgen production, we investigated whether a history of bilateral salpingo oophorectomy (BSO) is inversely associated with CVD mortality among women with DM2. RESEARCH DESIGN AND METHODS: Data were obtained from 7,977 women (a random subset of 564 had measurements of sex-steroid hormones) enrolled in the Study of Osteoporotic Fractures (SOF), a community-based, multicenter study that monitored women aged ≥65 years for a mean of 15.1 years. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. RESULTS: The average age at baseline was 71.5 years, with 6.3% and 18% of participants reporting a history of diabetes or BSO, respectively. In the subset of the SOF cohort with sex-steroid hormone measurements, those with DM2 had 43.6% significantly higher levels of free testosterone that were partly explained by age and adiposity, whereas total and free testosterone levels were lower in women with BSO than in those with intact ovaries. CVD mortality was elevated in women with DM2 without BSO (HR 1.95, 95% CI 1.62–2.35) as well as in women with DM2 and BSO (HR 2.56, 95% CI 1.79–3.65; P = 0.190 for interaction). Overall, BSO was not associated with CVD mortality (HR 1.05, 95% CI 0.89–1.23). CONCLUSIONS: The association of diabetes with CVD was not reduced by BSO, suggesting that ovarian hyperandrogenemia may not be a primary mechanism to explain the high risk for CVD among women with DM2.