Endogenous Sex Hormones and the Prospective Association with Cardiovascular Disease and Mortality in Men: the Tromsø Study

Objective: To study the impact of endogenous testosterone levels in community-dwelling men on later risk for myocardial infarction (MI) and all-cause, cardiovascular disease (CVD), and ischemic heart disease (IHD) mortality.

Design: Population-based prospective cohort study.

Methods: For the analyses, we used a cohort of 1568 randomly selected men, with sex-hormone data participating in the fourth Tromsø Study (1994-1995). Defined end points were first-ever MI (fatal or nonfatal), all-cause, CVD, and IHD mortality. A committee performed thorough ascertainment of end points, following a detailed protocol. Complete ascertainment of end points was until 30 September 2007 for all-cause mortality, until 31 December 2005 for CVD/IHD mortality, and until 31 December 2004 for first-ever MI. The prospective association between total and free testosterone and end points were examined using Cox proportional hazard regression, allowing for multivariate adjustment for age and cardiovascular risk factors.

Results: During follow-up, there were 395 deaths from all causes, 130 deaths from CVD and 80 deaths from IHD, while 144 men experienced a first-ever MI. There was a significant increase in all-cause mortality risk for men with free testosterone in the lowest quartile (<158 pmol/l) compared with the higher quartiles after age adjustment hazard ratios (HR 1.24, 95% confidence interval, CI 1.01-1.53) and after multivariate adjustments (HR 1.24, 95% CI 1.01-1.54). Total testosterone was not associated with mortality risk. Likewise, there were no significant changes in risk for first-ever MI across different total or free testosterone levels.

Conclusion: Men with free testosterone levels in the lowest quartile had a 24% increased risk of all-cause mortality.