Context The literature provides no clear answer as to whether low endogenous testosterone increases risk of cardiovascular disease (CVD) in healthy men.

Objective Our purpose was to estimate the predictive value of testosterone for CVD and to identify study features explaining conflicting results.

Data Sources Articles were identified by a Medline and Embase search and citation tracking.

Study Selection Eligible were prospective population-based cohort and nested case-control studies of testosterone and atherosclerosis, stroke, myocardial infarction, ischaemic heart disease, death from coronary heart disease or mortality.

Data extraction Two independent researchers re-expressed associations of testosterone and CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of testosterone for CVD.

Results and Conclusions 19 potentially eligible articles were identified. Overall, a weak independent association was found with an estimated summary RR of 0.89 for a change of one standard deviation in total testosterone level (95% CI 0.83 to 0.96). Age of study population and year of publication modified the relationship between testosterone and CVD. The estimated summary RR was 1.01 (0.95 to 1.08) for studies of men younger than 70 years of age, and 0.84 (0.76 to 0.92) for studies including men over 70 years of age. The latter studies showed a particular pronounced association if published after 1 January 2007. Results were largely confirmed by separate analyses of free- and bioavailable testosterone. The systematic review displayed no association between endogenous testosterone and risk for CVD in middle-aged men. In elderly men, testosterone may weakly protect against CVD. Alternatively, low testosterone may indicate a poor general health.