Prescription Testosterone is Associated with an Increased Risk of Anterior Cruciate Ligament Injury.

Purpose: To characterize the relationship between testosterone replacement therapy (TRT) and anterior cruciate ligament (ACL) injuries.

Methods: 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.

Results: 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.

Conclusion: 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 of evidence: Level III, retrospective comparative study.