The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data

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.