Oral contraceptive use and anterior cruciate ligament injury: comparison of active comparator new user cohort and case-control study designs

Mackenzie M Herzog,Virginia Pate,Jennifer L Lund,Christina D Mack,Jessica C Young,Stephen W Marshall

doi:10.1186/s40621-020-00282-x

Abstract

BackgroundThis study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies.MethodsActive comparator new user cohort analysis of women aged 13–45 years in the United States from the IBM MarketScan Commercial Claims and Encounters database who newly-initiated low-dose OCs (exposed) or underwent intrauterine device (IUD) insertion (comparison group) from 2000 to 2014. Women were followed for ACL injury starting 90 days after OC initiation or IUD insertion until OC or IUD discontinuation or end of continuous enrollment. Adjusted hazard ratios (adjHR) and 95% confidence intervals (CI) were estimated controlling for age. Secondary analysis replicated previously-published case-control studies assessing “ever” versus “never” OC use over 1- and 5-year periods among women who underwent ACL reconstruction compared to age-matched controls.ResultsIn the cohort analysis, 2,370,286 women initiated OCs and 621,798 underwent IUD insertion. There were 3571 (0.15%) ACL injuries during an average 370.6 days of continuous OC use and 1620 (0.26%) during an average 590.5 days of IUD use. No difference in risk of ACL injury was observed between OC initiators and IUD users (adjHR = 0.95; 95%CI 0.89, 1.01). The case-control analysis replicated the slight protective association observed in prior studies over a 5-year period (OR = 0.90; 95%CI 0.85, 0.94).ConclusionsThis cohort study suggests no association between OC use and ACL injury, while the case-control study suggested bias from uncontrolled confounding and selection factors may have influenced previous findings that suggested a protective association between OC use and ACL injury.

Highlights

This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies
While males sustain a larger absolute number of ACL injuries compared to females, studies have shown that females have higher incidence rates of ACL injury than males when accounting for participation in gendercomparable activities, such as basketball, soccer, and other collegiate sports (Brophy et al 2015; Whitney et al 2014; Lyle et al 2014; Flaxman et al 2014; Kosaka and Nakase 2016; Gould et al 2016; Rahr-Wagner et al 2014; Konopka et al 2016; Bates et al 2016; Arendt et al 1999)
There was no difference in crude risk of ACL injury comparing OC initiators to intrauterine device (IUD) users (Fig. 3; hazard ratio (HR) = 1.00, 95% confidence intervals (CI) 0.94, 1.06)

Summary

Introduction

This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies. Several risk factors have been proposed and investigated to explain the higher injury rates observed in females, including biological, biomechanical, and psychological factors (Kosaka and Nakase 2016; Gould et al 2016; Rahr-Wagner et al 2014; Konopka et al 2016; Bates et al 2016). Other studies have found a potential cyclic influence on risk of ACL injury among women, suggesting that fluctuation in serum estrogen level may affect ACL structure and composition (Hewett et al 2007). Biomechanical studies have identified increased muscle fatigue and knee laxity during the ovulation phase of the menstrual cycle, suggesting potential effects of hormone fluctuation on musculoskeletal and physiological performance (Sarwar et al 1996)

Methods

Results

Discussion

Conclusion