Endogenous Testosterone Levels and the Risk of Incident Cardiovascular Events in Elderly Men: The MrOS Prospective Study

Context: Observational studies show discordant links between endogenous testosterone levels and cardiovascular diseases (CVD). Objective: We assessed whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CVD in community-dwelling elderly men. Design, Setting and Participants: Prospective study of incident CVD among 552 men ≥ 65 years in the MrOS Sleep Study without prevalent CVD and no testosterone therapy at baseline. Outcomes: Fasting serum levels of total testosterone and estradiol were measured using liquid chromatography-mass spectrometry, and SHBG by chemiluminescent substrate. The association of sex hormones and SHBG with incident coronary heart disease (CHD), cerebrovascular (stroke and transient ischemic attack) and peripheral arterial disease (PAD) events were assessed by quartile and per SD increase in proportional hazards models. Results: After 7.4 years, 137 men (24.8%) had at least 1 CVD event: 90 CHD, 45 cerebrovascular and 26 PAD. The risk of incident CVD events was not associated with quartiles of baseline sex hormones or SHBG (all P ≥ 0.16). For +1 SD in total testosterone, the multivariate-adjusted hazard ratio was 1.04 (95% CI, 0.80-1.34) for CHD, 0.86 (0.60-1.25) for cerebrovascular, and 0.81 (0.52-1.26) for PAD events. When analyzed as continuous variables or comparing highest to low quartile, levels of bioavailable testosterone, total estradiol, testosterone/estradiol ratio and SHBG were not associated with CVD events. Conclusions: In community-dwelling elderly men, endogenous levels of testosterone, estradiol, and SHBG were not associated with increased risk of CHD, cerebrovascular, or PAD events. These results are limited by the small number of events and should be explored in future studies.