Long-Term Cardiovascular Safety of Testosterone-Replacement Therapy in Middle-Aged and Older Men: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION

The cardiovascular safety of testosterone-replacement therapy (TRT) for middle-aged and older men with low to low-normal levels of testosterone remains unclear.

METHODS

We systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing TRT versus placebo for men aged ≥ 40 years old with hypogonadism or low to low-normal testosterone levels (≤ 14 nmol/L), and at least 12 months of follow-up. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) applying a random-effects model and using R version 4.3.1 for statistical analyses.

RESULTS

We included 23 RCTs comprising 9280 men with testosterone deficiency, of whom 4800 (51.7%) were randomized to TRT. The mean age was 64.6 years, and the baseline total testosterone was 9.17 nmol/L. Placebo and TRT had similar rates of all-cause mortality (RR 0.85; 95% CI 0.60-1.19; p = 0.33). There was a significant increase in the incidence of cardiac arrhythmias (RR 1.53; 95% CI 1.20-1.97; p < 0.01). There was no significant difference between groups in cardiovascular mortality (RR 0.85; 95% CI 0.65-1.12; p = 0.25), stroke (RR 1.00; 95% CI 0.67-1.50; p = 0.99), and myocardial infarction (RR 0.94; 95% CI 0.69-1.28; p = 0.70).

CONCLUSION

In men with low to low-normal testosterone, aged 40 and above, TRT did not increase all-cause mortality, cardiovascular mortality, stroke, or myocardial infarction, but increased the incidence of cardiac arrhythmias.

REGISTRATION

PROSPERO identifier number CRD42024502421.