Background:Female patients are more likely than male patients to experience various musculoskeletal (MSK) injuries. Because MSK tissues are sensitive to the female hormones relaxin, estrogen, and progesterone, studies have examined whether hormonal contraceptives, which change female hormone levels, can alter the female MSK injury risk. These studies have reached contradictory conclusions, leaving unclear the influence of hormonal contraception on female MSK injury risk.Hypothesis:Hormonal contraceptives act to decrease female soft tissue injury risk and soft tissue laxity.Study Design:Systematic review; Level of evidence, 3.Methods:Reviewers searched for clinically relevant studies evaluating the relationship between hormonal contraceptive use and soft tissue injuries, soft tissue laxity, muscle injuries, and muscle strength in the PubMed, Cochrane, Scopus, CINAHL, and Embase databases. Studies meeting inclusion criteria were scored by 2 independent researchers for risk of bias, imprecision, inconsistency, and indirectness with a template designed using the British Medical Journal Clinical Evidence GRADE (Grades of Recommendation Assessment, Development and Evaluation) scoring system and GRADEPro guidelines. Scores were uploaded into the GRADEPro scoring system software, which calculated each study’s final GRADE score (very low, low, moderate, or high quality).Results:A total of 29 studies met inclusion criteria. Of the 7 studies evaluating oral contraceptive (OC) use and soft tissue injury risk, only 2 received a high quality-of-evidence score; all other studies received a very low score. The high-quality studies concluded that OC use decreases anterior cruciate ligament (ACL) injury risk. Only 1 of the 10 studies evaluating OC use and soft tissue laxity was found to have a high quality of evidence; this study determined that OC use decreases ACL laxity.Conclusion:Higher quality studies suggest that OCs decrease a female patient’s risk of ACL injuries and ACL laxity. The strength of these findings, however, is weak. Female patients are up to 8 times more likely to tear their ACLs than male patients. OCs may serve a therapeutic role in decreasing the sex disparity in ACL injury rates.

Background: Women are 2 to 9 times more likely to experience an anterior cruciate ligament (ACL) injury than men. Various hormones including relaxin, progesterone, and estrogen influence ACL strength. Oral contraceptives (OCs) alter these hormone levels; however, studies have yet to comprehensively compare different OCs’ effects on the ACL. Hypothesis: OCs with increased progestin-to-estrogen ratios will (1) increase ACL collagen expression, (2) decrease ACL matrix metalloproteinase expression, and (3) increase ACL strength. Study Design: Controlled laboratory study. Methods: Untreated female rats were compared with rats treated with 1 of 5 clinically used OCs: norethindrone (NE) only, NE plus ethinylestradiol (EE), etynodiol diacetate (ED) plus EE, norgestimate (NG) plus EE, and drospirenone (DS) plus EE. Doses were scaled from human doses to account for differences in bioavailability and body weight, and OCs were administered daily via oral gavage for 4 rat estrous cycles (20 days). A total of 36 rats were then sacrificed (6 rats/group). ACLs underwent biomechanical testing to assess ACL strength, stiffness, and maximum load before failure. ACL specimens were also isolated for quantitative real-time polymerase chain reaction analysis to assess collagen, matrix metalloproteinase, and relaxin receptor–1 expression. Results: While the primary structural property of interest (ACL maximum load before failure) was not significantly improved by OC treatment, the main material property of interest (ACL strength) in rats treated with NE only, DS + EE, ED + EE, and NE + EE was significantly increased compared with untreated controls ( P = .001, P = .004, P = .004, and P = .04, respectively). The order from strongest to weakest ACLs, which was also the same order as the highest to lowest progestin-to-estrogen ratios, was groups treated with NE only, DS + EE, ED + EE, NE + EE, and lastly NG + EE. Higher ratio formulations also increased the expression of type I collagen ( P = .02) and decreased the expression of matrix metalloproteinase–1 ( P = .04). Conclusion: OC formulations with higher progestin-to-estrogen ratios may be more protective for the ACL than formulations with lower ratios. Clinical Relevance: OC formulations with high progestin-to-estrogen ratios may benefit female athletes by reducing their ACL injury risk by decreasing the effects of relaxin on the ACL.

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