Journal of experimental orthopaedics · 2026
Oral contraceptive use and anterior cruciate ligament injury or reconstruction in women: A systematic review and meta-analysis of very low-certainty evidence.
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Kobayashi Eiki Nicholas, Silva Natalia Zampa, de Azevedo Laura Amaral Coelho, de Abreu Maria Eugênia Cammarota, Malpaga Juliano Mangini Dias, de Oliveira Diego Escudeiro, Jorge Pedro Baches
Аннотация
PURPOSE: To determine whether oral contraceptive use is associated with anterior cruciate ligament injury or reconstruction in women and to examine whether associations vary according to age, contraceptive formulation, duration of use and outcome definition.
METHODS: PubMed, Scopus, Embase and Latin American and Caribbean Health Sciences Literature (LILACS) were searched through 31 July 2026 (LILACS rerun with multilingual terms on 16 September 2026). Comparative observational studies were meta-analysed. The primary analysis pooled adjusted or matched odds ratios (ORs) for reconstruction or operatively treated injury using random-effects restricted maximum-likelihood models with Hartung-Knapp-Sidik-Jonkman confidence intervals (CIs). Risk of bias was assessed with risk of bias in nonrandomised studies of exposures and certainty with grading of recommendations assessment, development and evaluation.
RESULTS: Ten studies were included; seven were meta-analysed. The primary analysis (four studies) showed no clear association (OR, 0.89; 95% CI, 0.77-1.02; I 2 = 84%; τ 2 = 0.01; 95% prediction interval, 0.66-1.19). Two crude athlete studies and the active-comparator cohort (hazard ratio, 0.95; 95% CI, 0.89-1.01) also had CIs including 1. Adding one crude database estimate yielded OR 0.85 (95% CI, 0.74-0.98; I 2 = 90%; 95% prediction interval, 0.61-1.19). Leave-one-out results were unstable. The certainty of evidence was very low.
CONCLUSIONS: The primary adjusted or matched analysis did not establish a clear association between oral contraceptive use and anterior cruciate ligament reconstruction or operatively treated injury; substantial heterogeneity, residual confounding and very low certainty of evidence preclude causal interpretation. Current evidence does not support initiating or selecting oral contraceptives for anterior cruciate ligament injury prevention. Well-designed prospective studies with standardised exposure and outcome definitions are needed.
LEVEL OF EVIDENCE: Level IV, systematic review of observational studies.
METHODS: PubMed, Scopus, Embase and Latin American and Caribbean Health Sciences Literature (LILACS) were searched through 31 July 2026 (LILACS rerun with multilingual terms on 16 September 2026). Comparative observational studies were meta-analysed. The primary analysis pooled adjusted or matched odds ratios (ORs) for reconstruction or operatively treated injury using random-effects restricted maximum-likelihood models with Hartung-Knapp-Sidik-Jonkman confidence intervals (CIs). Risk of bias was assessed with risk of bias in nonrandomised studies of exposures and certainty with grading of recommendations assessment, development and evaluation.
RESULTS: Ten studies were included; seven were meta-analysed. The primary analysis (four studies) showed no clear association (OR, 0.89; 95% CI, 0.77-1.02; I 2 = 84%; τ 2 = 0.01; 95% prediction interval, 0.66-1.19). Two crude athlete studies and the active-comparator cohort (hazard ratio, 0.95; 95% CI, 0.89-1.01) also had CIs including 1. Adding one crude database estimate yielded OR 0.85 (95% CI, 0.74-0.98; I 2 = 90%; 95% prediction interval, 0.61-1.19). Leave-one-out results were unstable. The certainty of evidence was very low.
CONCLUSIONS: The primary adjusted or matched analysis did not establish a clear association between oral contraceptive use and anterior cruciate ligament reconstruction or operatively treated injury; substantial heterogeneity, residual confounding and very low certainty of evidence preclude causal interpretation. Current evidence does not support initiating or selecting oral contraceptives for anterior cruciate ligament injury prevention. Well-designed prospective studies with standardised exposure and outcome definitions are needed.
LEVEL OF EVIDENCE: Level IV, systematic review of observational studies.