The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood.

To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to determine the effects of TRT on patient important outcomes and adverse events in hypogonadal men.

We searched Ovid Medline, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus, from inception to 2 March 2017.

Randomized clinical trials assessing the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning total testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism.

Reviewers working independently and in duplicate assessed the quality of RCTs and collected data on patient characteristics, interventions, and outcomes.

We found four RCTs (including 1779 patients) at low risk of bias. Compared with placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17; 95% confidence interval (CI), 0.01, 0.34; n = 1383], erectile function (SMD: 0.16; 95% CI, 0.06, 0.27; n = 1344), and sexual satisfaction (SMD: 0.16; 95% CI, 0.01, 0.31; n = 676) but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis (relative risk: 8.14; 95% CI, 1.87, 35.40; n = 1579) compared with placebo but had no significant effect on lower urinary tract symptoms.

In hypogonadal men, TRT improves sexual desire, erectile function and sexual satisfaction; however, it increases the risk of erythrocytosis.