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. 2024;44(1):113-123.

Menstrual Cycle Hormone Relaxin and ACL Injuries in Female Athletes: A Systematic Review

Emily A Parker  1   2 , Kyle R Duchman  1 , Alex M Meyer  1   3 , Brian R Wolf  1 , Robert W Westermann  1
Affiliations

Menstrual Cycle Hormone Relaxin and ACL Injuries in Female Athletes: A Systematic Review

Emily A Parker et al. Iowa Orthop J. 2024.

Abstract

Background: Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined. Recent data suggests that the collagen-degrading menstrual hormone relaxin may cyclically impact female ACL tissue quality. This review aims to identify any correlation between menstrual relaxin peaks and rates of female ACL injury.

Methods: A systematic review was performed, utilizing the MEDLINE, EMBASE, and CINAHL databases. Included studies had to directly address relaxin/female ACL interactions. The primary outcome variable was relaxin proteolysis of the ACL, at cellular, tissue, joint, and whole-organism levels. The secondary outcome variable was any discussed method of moderating relaxin levels, and the clinical results if available.

Results: AllThe numerous relaxin receptors on female ACLs upregulate local collagenolysis and suppress local collagen production. Peak serum relaxin concentrations (SRC) occur during menstrual cycle days 21-24; a time phase associated with greater risk of ACL injury. Oral contraceptives (OCPs) reduce SRC, with a potential ACLprotective effect.

Conclusion: A reasonable correlative and plausible causative relationship exists between peak relaxin levels and increased risk of ACL injury in females, and further investigation is warranted. Level of Evidence: III.

Keywords: acl rupture; female athlete physiology; injury prevention; sex-based risk factors; sports medicine.

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Conflict of interest statement

Disclosures: EAP and AMM declare no competing interests. KRD reports educational support from Wardlow Enterprises, other support from Smith & Nephew, and other support from Stryker; outside the submitted work. BWW reports consulting fees, royalty or license fees, and other support from Linvatec Corp; outside the submitted work. RWW reports personal fees from Smith & Nephew, personal fees from Medical Device Business Systems, personal fees from Linvatec Corp, non-financial support and other support from Smith & Nephew, other support from Arthrex, and other support from Wardlow Enterprises; outside the submitted work.

Figures

Figure 1
Figure 1
Menstrual Cycle Hormone Peaks, Molecular Effects. Estrogen levels peak first, increasing expression of relaxin receptors in the body and increasing global synthesis of MMPs. The drop in estrogen triggers ovulation, and the remains of that ovarian follicle form the corpus luteum. As a temporary endocrine body, the corpus luteum secretes progesterone to prepare the endometrium for pregnancy and to sustain itself. It also synthesizes and releases relaxin, which binds receptors and activates MMPs recently upregulated by estrogen while suppressing de novo collagen synthesis. Relaxin is active during the luteal phase, chiefly CD21-24.
Figure 2
Figure 2
Estimated Lifetime Days of Relaxin-Induced Collagen Lysis, Female ACL Laxity. Relaxin, via G-protein coupled receptors, binds at the knee joint synovium to enact intra-articular changes. In stabilizing structures, the production of collagen-degrading enzymes is increased. Within the joint space, expression of inflammatory enzymes is also increased. This creates an environment not conducive to connective tissue stability, which recurs with each menstrual cycle and peak relaxin level.
Figure 3
Figure 3
Hypothesized "Triple Hit" Scenario Resulting in Increased Female ACL Risk. The trio of factors which impact high rates of female ACL tear are biomechanical, anatomical, and hormonal. The biomechanical factor can be ascribed to relative weakness of hamstrings, and the anatomical factor is the result of an increased Q-angle. The hormonal factor has previously been ill-defined, but relaxin-induced degradation of collagen could be the major contributing component.
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