The Effect of Estrogen on Anterior Cruciate Ligament Structure and Function: A Systematic Review

Abstract

Background: There is a widely acknowledged biological sex difference in anterior cruciate ligament (ACL) injuries, with females at a significantly higher risk compared to males. Due to the sex difference, the influence of the sex hormone estrogen has been investigated. Consequently, the aim of this study through reviewing current literature was to explore the association fluctuations in estrogen concentration during the menstrual cycle and altered ACL extracellular matrix (ECM) structure and subsequent function.Methodology: Scopus and PubMed search engines were selected to perform a series of searches in April and May 2022. An exclusion criterion was implemented, and each article was critically analysed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) structure was utilised to outline how the literature selection was made.Results: Estrogen surges were concurrent with increases in knee laxity. A time delay of 2-3 days could be identified between the estrogen surges and increases in knee laxity, indicating the days that could hold the highest risk of injury due to ligaments being unable to tolerate normal loads. Moreover, specific to ACLs, increasing estrogen concentrations are coupled with reduced ultimate tensile stress and linear stiffness. The mechanisms by which estrogen impacts ACL function are still unclear; however, it has been suggested that estrogen causes alterations to ECM structure either by decreasing type I collagen production and ACL fibroblast proliferation, or by reducing collagen crosslinking via lysyl oxidase inhibition. Conclusions:The findings of this review highlight that increases in estrogen concentration are associated with structural and cellular changes within ACLs, specifically decreased type I collagen content and crosslinking.Subsequent increases in knee laxity indicate estrogen should be considered a potential risk factor for ACL injuries in female athletes.