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.
Testosterone replacement therapy was associated with increased risk of clinical fractures compared with placebo.
No significant difference between TRT and placebo was observed for major osteoporotic fractures (hip, spine, wrist, and arm).
TRT was not associated with a significantly different risk of vertebral fractures compared with placebo.
TRT was not associated with a significantly different risk of hip fractures compared with placebo.
Only two RCTs met inclusion criteria for the meta-analysis, representing a limited evidence base.
This research systematically reviewed and pooled data from randomized controlled trials to examine whether testosterone replacement therapy (TRT) affects fracture risk in men with hypogonadism (abnormally low testosterone). Despite TRT's well-known benefits for bone density, whether it actually reduces fractures in this population had remained unclear. The researchers identified only two high-quality trials involving a combined total of 2,711 men that met their strict inclusion criteria. The analysis found that men receiving TRT had a higher overall rate of clinical fractures compared to those receiving placebo — about 55% higher relative risk. However, when looking specifically at the most serious fracture types (major osteoporotic fractures such as hip, spine, wrist, and arm fractures), there was no statistically significant difference between TRT and placebo groups. Similarly, hip fractures and vertebral (spine) fractures analyzed individually showed no significant difference between groups. This suggests the elevated overall fracture risk associated with TRT in this analysis was driven largely by less severe, non-major fractures. This research suggests that while TRT may be linked to more minor fractures — possibly because increased physical activity or other behavioral changes accompany treatment — it does not appear to increase the risk of the most clinically serious fractures. However, the findings are based on only two studies, and the evidence base remains very limited. The wide confidence intervals and variable heterogeneity across outcomes highlight the need for larger, long-term randomized trials before firm conclusions can be drawn about TRT's effect on fracture risk in hypogonadal men.
Upload your bloodwork. We'll cross-reference your results against this study and 4,700 others.
Upload Your LabsAnagnostis P, Divaris E, Zidrou M, Kassi E, Tournis S. (2026). Effect of testosterone replacement therapy on fracture risk in hypogonadal men: A systematic review and meta-analysis of randomized controlled trials.. Maturitas. https://doi.org/10.1016/j.maturitas.2026.108961