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

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Oral contraceptive use and anterior cruciate ligament injury: comparison of active comparator new user cohort and case-control study designs Mackenzie M. Herzog1,2,3,4* , Jessica C. Young1, Jennifer L. Lund1, Virginia Pate1, Christina D. Mack1,3 and Stephen W. Marshall1,2,4

Abstract Background: This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies. Methods: Active 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. Results: In 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). Conclusions: This 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. Keywords: Anterior cruciate ligament, Female, Knee injuries, Oral contraceptives

* Correspondence: [email protected] 1 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, McGavran Greenberg Hall, CB #7435, Chapel Hill, NC 27599-7435, USA 2 University of North Carolina Injury Prevention Research Center, Chapel HIll, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit