The Relationship Between Exogenous Testosterone Use and Risk for Primary Anterior Cruciate Ligament Rupture

In the United States, testosterone therapy has markedly increased in recent years. Currently, there is a paucity of evidence evaluating the risk of ligamentous injuries in patients taking testosterone replacement therapy (TRT).

The purpose of this study was to quantify the association between TRT and the incidence of anterior cruciate ligament (ACL) injuries and the subsequent risk of ACL reconstruction (ACLR) failure. It was hypothesized that individuals receiving TRT would demonstrate an increased risk for index ACL injury and ACL rerupture.

Cohort study; Level of evidence, 3.

This is a retrospective cohort study utilizing the PearlDiver database. Records were queried between 2011 and 2020 for patients aged 18 to 59 years who filled a testosterone prescription. A matched control group based on age, sex, Charlson Comorbidity Index, tobacco use, diabetes, and hypothyroidism consisted of patients aged 18 to 59 years who had never filled a prescription for exogenous testosterone. International Classification of Diseases, 9th and 10th Revisions and Current Procedural Terminology (CPT) codes were utilized to identify patients with ACL injuries and those undergoing reconstruction. Multivariable logistic regression was used to compare rates of ACL injury at 6 months, 1 year, and 2 years after initiating TRT. ACLR failure was also examined at 1-year intervals for 5 years for individuals filling a TRT prescription.

A total of 851,816 patients were enrolled, with 425,908 patients in the TRT and control groups, respectively. The TRT cohort was significantly more likely to experience an ACL tear during 6-month (OR, 2.66; 95% CI, 2.17-3.26), 1-year (OR, 2.46; 95% CI, 2.11-2.86), and 2-year (OR, 2.22; 95% CI, 1.98-2.48) periods. The rate of reconstruction failure did not differ between the 2 cohorts at up to 5 years of follow-up (P > .05).

Patients receiving TRT were significantly more likely to sustain a primary ACL rupture but were not at a statistically significant increased risk of reconstruction failure.