Disclosure(s): No financial relationships to disclose
Disclosure(s):
Jack Paradis, BA: No financial relationships to disclose
Objectives: Testosterone replacement therapy (TRT) is increasingly prescribed to adult men for the treatment of hypogonadism and age-related testosterone decline. Although TRT has demonstrated clinical benefits, its effects on the musculoskeletal system remain poorly understood. Insights from anabolic-androgenic steroid (AAS) research raise concerns that exogenous testosterone, particularly at supraphysiologic levels, may adversely affect tendon and ligament integrity through altered collagen turnover and impaired tendon remodeling. Importantly, AAS is often used at supraphysiologic doses for performance enhancement and has been repeatedly linked to tendon and ligament injury. In contrast, TRT is prescribed to restore physiologic testosterone levels under medical supervision and therefore differs in both intent and dosing. Understanding whether similar risks exist with TRT is critical given a 27% rise in prescriptions from 2018 to 2022. Accordingly, the objective of this study was to systematically identify, evaluate, and synthesize peer-reviewed evidence on the association between TRT and the risk of tendon and ligament injuries in adult men. Methods: Following PRISMA 2020 guidelines, PubMed, Embase, and Scopus were searched from inception to July 2025 using terms for 'testosterone' and 'tendon' or 'ligament' injuries. Eligible studies involved adult males (>=18 years) receiving TRT while reporting tendinous or ligamentous injuries compared with non-TRT or matched controls. Two reviewers independently screened titles, abstracts, and full texts, with a third reviewer resolving disagreements. Data extraction included authors, year, sample size, age range, TRT minimum duration, injury type(s), and adjusted odds ratios (aORs) with confidence intervals at one- and two-year follow-up. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), and quality was rated using the Agency for Healthcare Research and Quality (AHRQ) checklist. Results: The database search identified 481 records; 411 remained after duplicate removal and underwent title/abstract screening. A total of 10 full-text articles were reviewed, with 7 meeting inclusion criteria (Figure 1). All studies were retrospective cohort studies using the PearlDiver database published from 2023 to 2025. The rotator cuff, Achilles and quadriceps tendons, and the anterior cruciate ligament (ACL) were each evaluated in two studies; the patellar and distal biceps tendons were each evaluated in one study. Across studies, TRT cohorts ranged from 112,242 to 345,369 patients (Table 1). Most cohorts enrolled middle-aged to older adults: four studies used 35-75 years with other studies using a variety of age ranges spanning age 18-90. All studies scored 9/9 on the NOS and were rated 'good' quality by AHRQ criteria. At one year, aORs ranged from 0.93 for Achilles tendon injury to 5.80 for quadriceps tendon injury, with additional estimates of 4.73 for rotator cuff, 4.68 for distal biceps, 2.42 for ACL, 2.06 for patellar, 1.59 for quadriceps, and 1.35 for rotator cuff. At two years, aORs ranged from 1.09 for Achilles tendon injury to 3.13 for ACL injury, with additional estimates of 2.14 for patellar, 2.12 for ACL, 1.38 for Achilles, 1.32 for quadriceps, 1.31 for rotator cuff, and 1.31 for any tendon. Conclusions: Across large claims-based cohorts, TRT in adult males is associated with higher odds of tendon and ligament injuries, with estimates of similar magnitude at one and two years where both were reported. Quadriceps tendon injury showed the highest odds at one year (aOR 5.80), whereas Achilles tendon injury showed the lowest (aOR 0.93-1.38). Collectively, these studies demonstrate an increased risk of tendon and ligament injury with TRT. Clinical implications center on patient counseling: discuss the risks of TRT with current or prospective users and incorporate these considerations into shared decision-making, coordinating with the prescribing clinician when appropriate. Prospective or registry-linked studies with laboratory-confirmed hypogonadism and standardized exposure and activity reporting are needed to clarify causality and define safe therapeutic windows.
