Sex Hormones and Cardiovascular Risk in Type 2 Diabetes: Cohort Study of the LookAHEAD Trial

OBJECTIVE To investigate the association of sex hormones at baseline and 1 year after a lifestyle intervention on cardiovascular (CV) risk in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This prospective study, following the Look AHEAD: Action for Health in Diabetes (LookAHEAD) trial, of 2,260 adults with T2D, included measurements of sex hormones and sex hormone binding globulin (SHBG). Baseline levels and 1-year changes were divided into sex-specific tertiles to assess the association with CV events (n = 488 events) and weight loss interactions. RESULTS In men, higher baseline total testosterone was associated with lower CV risk (hazard ratio [HR] = 0.74; 95% CI 0.56–0.97). In men with ≥7% weight loss, SHBG increases were inversely associated with CV risk (HR = 0.47; 95% CI 0.26–0.85). In men with <7% weight loss, increases in estradiol were associated with CV risk (second vs. first estradiol tertile: HR = 1.64 [95% CI 1.13–2.38]; third vs. first estradiol tertile: HR = 1.88 [95% CI 1.29–2.73]). No associations were detected in women. CONCLUSIONS In men with T2D, but not women with T2D, sex hormones were associated with CV events.