Oral Testosterone Therapy in Hypogonadal Men: A Comprehensive Systematic Review and Meta-Analysis of Safety, Efficacy, and Secondary Health Outcomes
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Objective
To conduct a systematic review and meta-analysis to evaluate the safety and efficacy of oral testosterone therapy in hypogonadal men. The primary outcome is the assessment of safety, focusing on cardiovascular risks, liver toxicity, and prostate safety. Secondary outcomes include evaluations of bone mass, cardiovascular benefits, cognitive function, and potential reductions in mortality.
Methods
A systematic search was conducted using databases such as PubMed, Embase, and Cochrane Library, identifying peer-reviewed studies published until August 2024. The search included randomized controlled trials (RCTs), cohort studies, and large clinical trials. The studies involved a total of 3,183 hypogonadal men. Data were extracted and analyzed to assess primary and secondary outcomes. Statistical methods for meta-analysis included fixed-effects and random-effects models to calculate pooled estimates and assess heterogeneity.
Results
The analysis included 21 studies, encompassing a total of 3,183 hypogonadal men. Oral testosterone therapy demonstrated a safety profile comparable to other testosterone replacement therapies (TRT). No significant increase in liver toxicity was observed, supported by studies showing no liver damage after long-term oral testosterone undecanoate (TU) administration. Cardiovascular safety results were mixed; some studies noted minor increases in systolic blood pressure, but there was no consistent evidence of a significant increase in major cardiovascular events compared to other TRT forms. The prostate safety profile was consistent with existing TRT modalities, with only minor increases in prostate-specific antigen (PSA) levels noted.Secondary outcomes were generally favorable: bone density improved, fat mass was reduced, and there were indications of cognitive benefits, although these findings varied across studies. However, the evidence for mortality reduction was inconclusive, with no strong data supporting a significant effect of oral testosterone on reducing mortality.
Conclusion
Oral testosterone therapy appears to be a safe and effective treatment for hypogonadal men, with a risk profile comparable to other TRT forms. It offers potential benefits in bone health and cognitive function but requires careful monitoring of cardiovascular health and prostate safety during treatment. The findings suggest that oral testosterone therapy can be a valuable option for hypogonadal men, though long-term studies are needed to better understand its full range of effects, particularly concerning mortality and cardiovascular outcomes.
