Sex steroids and all-cause and cause-specific mortality in men

Sex steroid levels are related to metabolic outcomes that could convey higher risk of premature death.

We examined whether total or free testosterone, dihydrotestosterone, and sex hormone-binding globulin levels are related to all-cause or cause-specific mortality in men. Data were obtained from the Massachusetts Male Aging Study, a population-based cohort study of 1709 men aged 40 to 70 years. Men were followed up for all-cause and cause-specific mortality.

Complete data were available for 1686 men, with 395 deaths occurring during 15.3 years of follow-up. With age adjustment, dihydrotestosterone and sex hormone-binding globulin levels were associated with ischemic heart disease mortality, and free testosterone level was associated with respiratory mortality. In multivariate-adjusted models, higher free testosterone (P=.02) and lower dihydrotestosterone (P=.04) levels were significantly associated with ischemic heart disease mortality, although the latter association was not robust to differences in model selection. The relative risk of death from ischemic heart disease per 1-SD lower free testosterone level was 0.80 (95% confidence interval, 0.64-0.99). Free testosterone level was significantly associated with respiratory mortality (P=.002), with a multivariate-adjusted relative risk per 1-SD lower free testosterone level of 1.90 (95% confidence interval, 1.24-2.92). Total testosterone level was unrelated to mortality, and sex hormone-binding globulin was not significantly associated with mortality after multivariate adjustment.

In men, endogenous sex steroid levels seem to have relatively weak associations with mortality. These data provide little support for the hypothesis that endogenous sex steroid levels are associated with risk of premature death but suggest that further investigation of the relationship between sex steroids and mortality from ischemic heart disease and respiratory disease may be warranted.