Cardiovascular Risks of Exogenous Testosterone Use Among Men: A Systematic Review and Meta-Analysis

Am J Med. 2017 Mar;130(3):293-305. doi: 10.1016/j.amjmed.2016.09.017. Epub 2016 Oct 14.


Purpose: We sought to evaluate whether exogenous testosterone therapy is associated with increased risk of serious cardiovascular events as compared with other treatments or placebo.

Methods: Study selection included randomized controlled trials (RCTs) and observational studies that enrolled men aged 18 years or older receiving exogenous testosterone for 3 or more days. The primary outcomes were death due to all causes, myocardial infarction, and stroke. Secondary outcomes were other hard clinical outcomes such as heart failure, arrhythmia, and cardiac procedures. Peto odds ratio was used to pool data from RCTs. Risk of bias was assessed using Cochrane Collaboration tool and Newcastle and Ottawa scale, respectively. The strength of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation Working Group approach.

Results: A total of 39 RCTs and 10 observational studies were included. Meta-analysis was done using data from 30 RCTs. Compared with placebo, exogenous testosterone treatment did not show any significant increase in risk of myocardial infarction (odds ratio [OR] 0.87; 95% CI, 0.39-1.93; 16 RCTs), stroke (OR 2.17; 95% CI, 0.63-7.54; 9 RCTs), or mortality (OR 0.88; 95% CI, 0.55-1.41; 20 RCTs). Observational studies showed marked clinical and methodological heterogeneity. The evidence was rated as very low quality due to the high risk of bias, imprecision, and inconsistency.

Conclusions: We did not find any significant association between exogenous testosterone treatment and myocardial infarction, stroke, or mortality in randomized controlled trials. The very low quality of the evidence precludes definitive conclusion on the cardiovascular effects of testosterone.

Keywords: Cardiovascular risks; Exogenous testosterone; Meta-analysis; Systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Arrhythmias, Cardiac / chemically induced
  • Cardiovascular Diseases / chemically induced*
  • Heart Failure / chemically induced
  • Humans
  • Male
  • Mortality
  • Myocardial Infarction / chemically induced
  • Stroke / chemically induced
  • Testosterone / adverse effects*
  • Testosterone / therapeutic use


  • Testosterone