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

  • Herzog, Mackenzie M.1, 2, 3, 4
  • Young, Jessica C.1
  • Lund, Jennifer L.1
  • Pate, Virginia1
  • Mack, Christina D.1, 3
  • Marshall, Stephen W.1, 2, 4
  • 1 University of North Carolina at Chapel Hill, McGavran Greenberg Hall, CB #7435, Chapel Hill, NC, 27599-7435, USA , Chapel Hill (United States)
  • 2 University of North Carolina Injury Prevention Research Center, Chapel HIll, USA , Chapel HIll (United States)
  • 3 Injury Surveillance and Analytics, Real-World Analytics Solutions, IQVIA, Durham, USA , Durham (United States)
  • 4 University of North Carolina at Chapel Hill, Chapel Hill, USA , Chapel Hill (United States)
Published Article
Injury Epidemiology
Springer (Biomed Central Ltd.)
Publication Date
Oct 19, 2020
DOI: 10.1186/s40621-020-00282-x
Springer Nature


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.

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