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.
Key Findings
Results
TRT was associated with a significant increase in the incidence of cardiac arrhythmias compared to placebo.
Risk ratio 1.53; 95% CI 1.20–1.97; p < 0.01
This was the only cardiovascular outcome for which TRT showed a statistically significant difference from placebo
Analysis used a random-effects model pooling data from 23 RCTs
Results
TRT and placebo had similar rates of all-cause mortality in middle-aged and older men with testosterone deficiency.
Risk ratio 0.85; 95% CI 0.60–1.19; p = 0.33
Result was not statistically significant
Study population comprised 9280 men with a mean age of 64.6 years and baseline total testosterone of 9.17 nmol/L
Results
TRT did not significantly differ from placebo in terms of cardiovascular mortality.
Risk ratio 0.85; 95% CI 0.65–1.12; p = 0.25
Result was not statistically significant
Analyzed across 23 RCTs with at least 12 months of follow-up
Results
TRT did not significantly increase the risk of stroke compared to placebo.
Risk ratio 1.00; 95% CI 0.67–1.50; p = 0.99
Result indicated no meaningful difference between TRT and placebo groups
Included men aged ≥40 years with hypogonadism or low to low-normal testosterone levels (≤14 nmol/L)
Results
TRT did not significantly increase the risk of myocardial infarction compared to placebo.
Risk ratio 0.94; 95% CI 0.69–1.28; p = 0.70
Result was not statistically significant
Analysis based on 23 RCTs comprising 9280 men, of whom 4800 (51.7%) were randomized to TRT
Methods
The meta-analysis included 23 randomized controlled trials comprising 9280 men with testosterone deficiency.
4800 men (51.7%) were randomized to TRT and the remainder to placebo
Mean age of participants was 64.6 years
Baseline total testosterone was 9.17 nmol/L
Eligible trials required at least 12 months of follow-up and enrolled men aged ≥40 years with hypogonadism or testosterone ≤14 nmol/L
Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov; PROSPERO identifier CRD42024502421
Braga M, Rivera A, Marinheiro G, Felix N, Carvalho P, Gewehr D, et al.. (2025). Long-Term Cardiovascular Safety of Testosterone-Replacement Therapy in Middle-Aged and Older Men: A Meta-analysis of Randomized Controlled Trials.. American journal of cardiovascular drugs : drugs, devices, and other interventions. https://doi.org/10.1007/s40256-025-00737-w