Cardiovascular disease (CVD) is the leading cause of death worldwide. The effects of
testosterone, the primary male
sex hormone, on cardiovascular risk have been of special interest due to the increased risk of CVD in men. Although it is well established that
testosterone levels decline and cardiovascular mortality increases with age, the association between
testosterone and CVD remains unclear. Observational and randomized studies on the effects of endogenous and exogenous
testosterone have produced conflicting data, and meta-analyses have been inconclusive, suggesting significant study heterogeneity. Despite a lack of adequately powered randomized controlled trials, large observational studies in the early 2010s led to advisories on the use of
testosterone replacement
therapy. Similar advisories have been mandated for certain types of
androgen deprivation
therapy. Additional research suggests that
testosterone shortens the heart-rate-corrected QT interval, improves
glycemic control, induces vasodilation, is prothrombotic, and has anti-
obesity effects, whereas associations with
atherosclerosis and
inflammation are less clear. Despite inconclusive evidence on cardiovascular risk and inconsistencies among clinical practice guidelines, millions of men continue to use
testosterone replacement and
androgen deprivation
therapy. In addition to summarizing clinical and preclinical data, this review provides insight on potential mechanisms of action of
testosterone on CVD, applications of this knowledge to clinical settings, and avenues for future research.