Long-Term Cardiovascular Safety of Testosterone-Replacement Therapy in Middle-Aged and Older Men: A Meta-analysis of Randomized Controlled Trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 40694252 · doi:10.1007/s40256-025-00737-w
What was done
Systematic review and random-effects meta-analysis (PROSPERO CRD42024502421) of randomized controlled trials (RCTs) from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. The review included RCTs comparing testosterone-replacement therapy (TRT) versus placebo in men aged 40 years or older with hypogonadism or low to low-normal testosterone (14 nmol/L or less) and at least 12 months of follow-up. The analysis synthesized 23 RCTs encompassing 9,280 men (4,800 [51.7%] randomized to TRT; mean age 64.6 years; mean baseline total testosterone 9.17 nmol/L).
What was found
Compared with placebo, TRT demonstrated: - All-cause mortality: RR 0.85 (95% CI 0.60–1.19; p = 0.33) - 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) - Myocardial infarction: RR 0.94 (95% CI 0.69–1.28; p = 0.70) - Cardiac arrhythmias: RR 1.53 (95% CI 1.20–1.97; p < 0.01)
Why it matters
This meta-analysis provides reassurance regarding major ischemic events and mortality with TRT in older hypogonadal men, while highlighting an elevated risk of cardiac arrhythmias that requires clinical monitoring.
Limits
The abstract does not report specific subtypes of cardiac arrhythmias (e.g., atrial fibrillation vs. ventricular arrhythmias), baseline cardiovascular comorbidities, TRT formulations or dosages, heterogeneity statistics, or risk of bias assessments across included trials.
Cited by
- supports There is no scientific evidence that testosterone therapy extends lifespan or promotes longevity.