Is the use of oral contraceptives associated with operatively treated anterior cruciate ligament injury? A case-control study from the Danish Knee Ligament Reconstruction Registry

Abstract

Background: The incidence of anterior cruciate ligament (ACL) injuries is 2 to 9 times higher in women than in men. In addition, in vitro studies have demonstrated that ACL is an estrogen target tissue, and some studies have therefore suggested a protective association between oral contraceptives (OC) and the likelihood of sustaining ACL injury.

Hypothesis: There is a protective association between OC use and the likelihood of operatively treated ACL injury.

Study design: Case-control study; Level of evidence, 3.

Methods: The study population included 4497 women with an operatively treated ACL injury registered in the Danish Knee Ligament Reconstruction Registry for the 2005 to 2011 period and 8858 age-matched controls with no ACL injury. The study evaluated exposure to OC use at the time of ACL injury (index date) and in the 5 previous years ("ever user") or no OC use ("never user"). Ever users were further classified as either new users (patients who redeemed their first prescription within the first year before the index date), long-term users (redeemed additional prescriptions 1 to 5 years before the index date), or recent users (redeemed their most recent prescription >1 year before the index date). Finally, a dose-response analysis of OC use was performed. Conditional logistic regression was used to calculate the relative risk (RR) with a 95% CI of sustaining an operatively treated ACL injury according to OC use.

Results: The adjusted RR associating OC with ACL injury was 0.82 (95% CI, 0.75-0.90) between ever users and never users. Furthermore, there was a decreased RR of sustaining ACL injury of 0.80 (95% CI, 0.74-0.91) in long-term users and 0.81 (95% CI, 0.72-0.89) in recent users. Using OC for more than 4 years did not seem to alter the likelihood of sustaining an operatively treated ACL injury.

Conclusion: This population-based pharmacoepidemiological study including 13,355 women indicates that a protective association exists between OC use and the likelihood of sustaining an operatively treated ACL injury. Although this study does indicate a protective association of OC use, OC should not be used as a prophylactic measure before additional clinical studies have further clarified the biological and causal association between OC use and the likelihood of sustaining operatively treated ACL injury.

Keywords: ACL; anterior cruciate ligament; injury; oral contraceptives.