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Clinicians frequently prescribe testosterone replacement therapy (TRT) to older men experiencing symptomatic testosterone deficiency. While the benefits for sexual health and body composition are well-documented, the musculoskeletal effects remain a subject of intense clinical debate. Recent evidence highlights critical testosterone replacement therapy risks that challenge the long-held assumption of bone protection in this population. Understanding these outcomes is essential for endocrine and geriatric practice.
Studies consistently show that TRT improves body composition by effectively increasing lean mass and reducing fat mass. Furthermore, meta-analyses indicate small-to-moderate increases in bone mineral density (BMD), specifically at the lumbar spine and hip. However, these surrogate measures do not always translate into clinical benefits for the patient. Specifically, most clinical trials demonstrate that physical performance improvements remain modest and vary significantly between individuals.
The landmark TRAVERSE fracture analysis provided a surprising perspective on skeletal safety. Researchers found that TRT did not lower the risk of clinical fractures in older men with hypogonadism. Instead, the study reported a higher incidence of fractures in the treatment group, showing a hazard ratio of 1.43. Consequently, experts suggest that TRT should not be viewed as a primary disease-modifying strategy for preventing falls or osteoporotic fractures. This finding emphasizes the need for careful risk assessment before initiating therapy.
Beyond bone health, observational data suggest a significant association between TRT initiation and tendon injury. Recent retrospective studies indicate that patients on TRT may face higher odds of experiencing surgically treated tendon ruptures, such as Achilles or quadriceps tears. A potential mechanism for this involves a temporal mismatch. While muscle capacity gains occur relatively quickly, the adaptation of tendons and bones to increased physical loading takes much longer. Therefore, patients may overexert their connective tissues before they are biologically ready.
For older men with confirmed hypogonadism, TRT offers functional benefits but requires vigilant management. Physicians must assess baseline fracture and tendon risks before starting treatment. Additionally, structured monitoring is necessary to align with evolving regulatory warnings regarding age-related low testosterone use. Careful patient selection remains the cornerstone of safe and effective endocrine therapy in the aging population.
No, recent large-scale trials like TRAVERSE indicate that TRT does not reduce fracture risk and may even lead to a higher incidence of clinical fractures compared to placebo in certain cohorts.
The risk may stem from a rapid increase in muscle strength that outpaces the slower adaptation of tendons to heavier loads, or from increased physical activity levels in previously sedentary patients returning to exercise.
Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Szarpak L et al. Testosterone replacement therapy in older men: skeletal outcomes and fracture risk. Aging Male. 2026 Dec 31. doi: 10.1080/13685538.2026.2655544. PMID: 41947034.
Snyder PJ et al. Testosterone Treatment and Fractures in Men with Hypogonadism. N Engl J Med. 2024;390(3):203-211. doi: 10.1056/NEJMoa2308836.
Hou B et al. Testosterone Replacement Therapy Increases Odds of Tendon Ruptures Treated Surgically. Orthop J Sports Med. 2024;12(6). doi: 10.1177/23259671241253456.
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