Has the Protective Effect of Hormonal Contraception Been Overestimated? A Systematic Review and Meta-analysis of Oral Contraceptive Pills and ACL Injury.

BACKGROUND

Hormonal contraception (HC), including oral contraceptive pills (OCPs) and long-acting reversible contraceptives, is widely used by reproductive-aged women for various medical indications. Emerging evidence suggests a possible association between HC use and reduced anterior cruciate ligament (ACL) injury risk; however, no meta-analysis has systematically evaluated this relationship.

PURPOSE: To determine whether HC use reduces the risk of ACL injury in females through a systematic review and meta-analysis.

STUDY

DESIGN

Meta-analysis; Level of evidence, 3.

METHODS

A systematic search of the PubMed, OVID (MEDLINE), and Embase databases was conducted from inception through March 2025 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were included if they reported ACL injury incidence among both HC users and nonusers. Data were synthesized using a random-effects meta-analysis to calculate a pooled risk ratio. Publication bias was evaluated using funnel plots and Egger regression.

RESULTS

Eight studies consisting of 18,103,890 participants met inclusion criteria. All studies evaluated OCPs, and 3 included other forms of HC. The pooled risk ratio for ACL injury among HC users versus nonusers was 0.88 (95% CI, 0.77-1.01). Heterogeneity was high (I2 = 97.3%), and Egger regression showed no significant publication bias (P = .426).

CONCLUSION

Hormonal contraceptive use, particularly OCPs, does not appear to reduce ACL injury risk in females. Given the potential side effects of HC and the lack of conclusive benefit, clinicians should not recommend HC use solely for injury prevention. Future research should focus on non-OCP preventive strategies for ACL injury, diverse athletic populations, and standardized reporting of HC formulations.