SUN-788 - Effect of Testosterone Replacement Therapy on Fracture Risk in Hypogonadal Men: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials

Objective: Testosterone replacement therapy (TRT) is the treatment of choice in men with hypogonadism. Although its beneficial effect on bone mineral density is well-established, the evidence regarding its impact on fracture risk remains inconclusive. The purpose of this study was to systematically review and meta-analyze the highest quality available evidence regarding the effect of TRT on fracture risk in hypogonadal men.
Study design: A systematic literature search was conducted in PubMed, Scopus and Cochrane databases from inception through 30 September 2025. Only randomized-controlled trials were eligible for inclusion. Outcomes were summarized using odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index was used in order to quantify heterogeneity.

Results: Initial search yielded 1,145 results after removal of duplicates, seven of which underwent full-text assessment. Finally, two studies were included in the qualitative and quantitative analysis (n=2,711). TRT was associated with increased risk of clinical fractures compared with placebo (OR 1.58, 95% CI 1.23-2.04, p< 0.0001, I2=0%). However, no difference between groups was observed when the analysis was restricted to major osteoporotic fractures (hip, spine, wrist, and arm) (OR 0.61, 95% CI 0.11-3.46, p=0.58, I2 64%). This was also the case for vertebral (OR 0.87, 95% CI 0.34-2.26, p=0.80, I2: 11%) and hip fractures (OR 0.99, 95% CI 0.33-2.93, p=0.98, I2: 0%), when analyzed separately.

Conclusion: This is the first meta-analysis on the topic, showing that TRT is associated with an increased incidence of predominantly non-major fractures, while the risk of major osteoporotic fractures, including hip and vertebral fractures, was not increased.

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