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Testosterone and Anterior Cruciate Ligament Injury and Reconstruction Outcomes: A Systematic Review and Meta-analysis
Dave Osinachukwu Duru1, David Kwan Ryung Lee1, Prushoth Vivekanantha2
1School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Context:
Testosterone influences connective tissue biology, neuromuscular performance, and postoperative recovery. However, its clinical impact on anterior cruciate ligament (ACL) injury risk and outcomes after ACL reconstruction (ACLR) remains unclear.
Objective:
To evaluate the association between testosterone replacement therapy (TRT) or endogenous testosterone levels and ACL tear incidence, ACLR revision, patient-reported outcome measures (PROMs), strength, and complications.
Data Sources:
Embase, Ovid MEDLINE, and PubMed were searched from inception to March 14, 2026.
Study Selection:
Studies evaluating TRT use or endogenous testosterone levels in relation to ACL tear incidence or outcomes after ACLR were included. Systematic reviews, narrative reviews, scoping reviews, letters, editorials, technical notes, conference abstracts without full-text publication, animal studies, cadaveric studies, case reports, and non-English studies were excluded.
Study Design:
Systematic review and meta-analysis.
Level Of Evidence:
Level 3.
Data Extraction:
Two reviewers independently extracted study characteristics, testosterone exposure, ACL tear incidence, ACLR revision, PROMs, strength outcomes, and complications. Random-effects meta-analyses pooled odds ratios for ACL tear incidence and ACLR revision. Study quality was assessed using the Methodological Index for Non-Randomized Studies and Cochrane Risk of Bias 2.0, and certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation.
Results:
Seven studies were eligible, comprising 1,178,891 patients, of whom 589,436 were TRT users. TRT use was associated with a significantly increased risk of primary ACL tear within 2 years (odds ratio [OR], 2.83; 95% CI, 1.74-4.62; I 2 = 95.4%), with consistent findings across sex-specific analyses. In contrast, there was no difference in ACLR revision rates at 2 years (OR 1.04; 95% CI 0.84-1.29; I 2 = 0%). One randomized trial demonstrated increased early postoperative lean mass with TRT, without differences in strength or PROMs. Increased ACL rupture risk was associated with higher testosterone levels in men, and lower levels in women. Higher testosterone levels did not adversely affect PROMs or complication rates after ACLR.
Conclusion:
TRT is associated with increased ACL tear risk at 2 years after initiation but does not appear to affect 2-year ACLR revision rates. Higher endogenous testosterone levels may influence ACL injury susceptibility in a sex-dependent manner, without impairing ACLR recovery.