To characterize the relationship between testosterone replacement therapy (TRT) and anterior cruciate ligament (ACL) injuries. A retrospective cohort study using a large insurance database was conducted. Patients who were prescribed TRT for at least 3 months were matched with controls who were not prescribed TRT. Rates of ACL tears were compared between the cohorts. Multiple subgroups were created based on age (<25 years, 25-35, 36-45, 46-55, 56-65, and 65+). Multivariable logistic regressions were performed to determine the association of TRT with ACL tears while accounting for demographic variables and comorbidities. After matching, there were 160,839 patients in both the TRT cohort and control cohort. The incidence of ACL injuries was 17.8 per 10,000 person-years (95% CI: 16.4-19.2) for patients who were prescribed TRT and 4.9 per 10,000 person-years (95% CI: 4.1-5.7) for controls (p<0.001). Within 2 years of filling a testosterone prescription for at least 3 months, 572 (0.35%) patients experienced an ACL injury compared to only 157 (0.10%) controls during the same follow-up period (OR: 2.77; 95% CI: 2.26-3.42, p<0.001). When stratified by age, all groups except the <25 years of age group demonstrated significantly higher rate of ACL tears (OR 3.91-12.3, p<0.001-0.009). When separated by sex, males on TRT were 3.13 (95% CI: 2.50-3.93, p<0.001) times more likely while females on TRT were 1.94 (95% CI: 1.13-3.41, p=0.018) times more likely to experience an ACL injury compared to controls. This study found that patients prescribed at least three months of TRT had a significantly higher incidence of ACL injuries compared to controls within a two-year follow-up period. Level III, retrospective comparative study.
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