Luis M Canal de Velasco, José Emiliano González Flores, Alberto Azcona Cervera, Jose Luis Morales Arteaga, María J Olivares Casas
Testosterone is a central regulator of skeletal muscle protein synthesis, connective tissue remodeling, bone homeostasis, erythropoiesis, and systemic metabolic function. Although testosterone replacement therapy (TRT) is an established treatment for male hypogonadism, its role in athletes and physically active populations, particularly in injury recovery and rehabilitation, remains controversial due to limited athlete-specific evidence and ethical and regulatory considerations. Because TRT indications and most outcome data are based on male endocrine reference ranges, the evidence synthesized in this review is predominantly derived from male cohorts. Therapeutic testosterone use in female athletes remains comparatively understudied and cannot be directly generalized given sex-specific physiology, hormonal baselines, and dosing frameworks. We conducted a semi-systematic narrative review of peer-reviewed literature (1990-December 2025) across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, complemented by manual reference screening. Eligible publications included clinical studies, observational investigations, translational models, reviews, and consensus statements addressing testosterone or TRT in musculoskeletal recovery, rehabilitation, and sports medicine contexts. Study selection followed a Preferred Reporting Items for Systematic reviews and Meta-Analyses-informed framework, yielding 25 studies for qualitative synthesis. Mechanistic evidence indicates that testosterone promotes skeletal muscle adaptation through androgen receptor signaling and anabolic pathways such as AKT-mTORC1 and insulin-like growth factor-1, while suppressing catabolic regulators including myostatin. Testosterone also enhances satellite cell activation, collagen turnover, bone formation, and tendon remodeling, with additional immunomodulatory effects that support tissue repair. Clinically, supportive data derive largely from hypogonadal, aging, or high-catabolic populations, suggesting that physiological testosterone restoration may mitigate disuse atrophy and improve recovery; however, prospective evidence in injured athletic cohorts remains limited. Ergogenic effects are most consistent for strength and power, whereas endurance outcomes are variable. Current evidence supports testosterone as a permissive modulator of musculoskeletal recovery rather than a universal performance strategy. TRT should be considered a targeted, medically supervised intervention integrated within rehabilitation, with strict regulatory oversight in competitive sport. Future athlete-focused studies are required to define indications, efficacy, and long-term safety.