Abstract P047: Circulating Testosterone and Sex Hormone-Binding Globulin Concentrations and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality in US Women

Introduction: It remains unclear whether circulating testosterone and sex hormone-binding globulin (SHBG) are associated with cardiometabolic disease risk and mortality. Hypothesis: Higher SHBG and lower testosterone levels are associated with reduced risk of incident type 2 diabetes (T2D), cardiovascular disease (CVD), and all-cause mortality in women. Methods: Baseline testosterone and SHBG measures were available on 11,314 women from the Nurses’ Health Study I and II, who were part of 9 separate nested case-control studies and were free of CVD, T2D, and cancer at study baseline. Total testosterone was assayed by a radioimmunoassay or liquid chromatography tandem mass spectrometry; SHBG was measured by an immunoassay. Free testosterone was calculated based on a standard clinical formula. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regressions, adjusted for study design characteristics, established risk factors and confounders including menopausal statues, hormone therapy, and continuous body mass index. Results: During up to 22 years of follow-up (215,120 person-years), 891 incident T2D cases, 1,089 CVD cases (fatal myocardial infarction, nonfatal coronary heart disease, and fatal/nonfatal stroke), and 1,818 deaths occurred. In multivariable analyses, circulating SHBG levels were inversely associated with incident T2D (comparing the highest to lowest quartiles, HR [95% CI]: 0.34 [0.24-0.47]; P trend <0.001) and all-cause mortality (HR: 0.78 [0.65-0.95]; P trend =0.03). Total testosterone was inversely associated with T2D (HR: 0.71 [0.53-0.96]; P trend =0.04), while free testosterone was positively associated with T2D (HR: 1.99 [1.44-2.75]; P trend <0.001) and all-cause mortality (HR: 1.22 [1.00-1.48]; P trend =0.02). No association was observed between SHBG, nor free or total testosterone and CVD. Conclusions: Lower circulating levels of SHBG and higher levels of free testosterone were associated with increased risk of T2D and all-cause mortality, but not CVD, in women.