Cardiovascular and prostate cancer risk associated to testosterone replacement therapy - a systematic review and meta-analysis of 41 randomized controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of 41 randomized controlled trials
PubMed 41673435 · doi:10.1038/s41443-026-01237-4
What was done
A systematic review and meta-analysis (PROSPERO CRD42024603054) following PRISMA guidelines evaluated the risks of major adverse cardiovascular events (MACE), prostate cancer events (PCaE), and clinically significant prostate cancer (CsPcE) associated with testosterone replacement therapy for late-onset hypogonadism. Searches in PubMed, ClinicalTrials.gov, and Cochrane Central identified 41 randomized controlled trials covering 11,161 participants. Pooled odds ratios (OR) were calculated using fixed- or random-effects models, with meta-regression and zero-event continuity corrections.
What was found
Testosterone therapy was not associated with a significant increase in any primary risk outcome: - MACE: OR 0.83 (95% CI: 0.52–1.32; I² = 53.2%) - PCaE: OR 0.88 (95% CI: 0.52–1.51; I² = 0.0%) - CsPcE: OR 1.13 (95% CI: 0.39–3.26; I² = 0.0%) Meta-regression showed that baseline comorbidities contributed to heterogeneity observed in the MACE analysis.
Why it matters
These findings provide high-level trial evidence reassuring clinicians and patients that short- to mid-term testosterone replacement does not elevate cardiovascular or prostate cancer risk.
Limits
Moderate statistical heterogeneity was present in the MACE analysis (I² = 53.2%), influenced by variations in baseline participant comorbidities. The confidence intervals for prostate cancer outcomes remain relatively wide due to low total event counts, and the available RCT data primarily reflect short- to mid-term rather than multi-year or lifetime follow-up.
Cited by
- supports Testosterone replacement therapy does not increase the risk of cancer.