Relaxin Influences Knee Laxity Changes Across the Menstrual Cycle

Abstract

Greater knee laxity is associated with an increased risk for anterior-cruciate ligament (ACL) injury, particularly in women. Research suggests that the hormone relaxin may influence the structural integrity of the ACL, rendering a weaker and more lax ligament. PURPOSE: To assess the impact of relaxin on knee laxity once progesterone and testosterone (potential endocrine antagonists) are accounted for. METHODS: College-aged females (166.0±5.7cm, 65.9±8.5kg, 20.8±2.9yr) provided blood samples for the first 6 days of menses and first 10 days of luteal phase of one menstrual cycle. Knee laxity was recorded as anterior knee laxity (AKL; mm), genu recurvatum (GR; °), and general joint laxity (GJL; score, 0-9), and dependent variables were calculated as mean (X), cyclic Δ (max – min), coefficient of variation (CV), and standard deviation (SD). Progesterone (P; ng/ml), testosterone (T; ng/dl), and relaxin (R; pg/ml) were analyzed via ELISA assays. The sum of the 6 greatest hormone concentrations during menses (M) and luteal phase (L) and the change in exposure from M to L (MLΔ) were calculated. Only subjects with captured R and P peak were included in analysis (n=18). M and MLΔ for each hormone were entered into backward stepwise (in: p=.05, out: p=.20) multiple linear regression models to predict each laxity measure. RESULTS: R and P were significantly different between M and L (p<.001, RM=22.2±29.4 vs. RL=147.0±96.3; p<.001, PM=5.8±1.8 vs. PL=89.7±36.6), whereas T was less variable (p=.07, TM=203.8±63.0 vs. TL=222.7±82.6). All laxity showed variation across the menstrual cycle (range [min-max]: AKL=5.9-7.6; GR=2.6-5.6; GJL=.8-2.1). Significant models were observed for GRX (p=.014; R2=.418; GRX=3.501+.1.024RMLΔ-.757RM-.395PMLΔ), GJLMLΔ (p=.044; R2=.253; GJLMLΔ=-.469RMLΔ-.440TM), and GJLX (p=.035; R2=.379; GJLX=-.317RM-.353PM-.440PMLΔ-.507TM). Models for AKLMLΔ, AKLCV, GRΔ, and GJLSD approached significance (all p<.075). CONCLUSION: Once controlling for P and T, R was a significant predictor of knee laxity mean and cyclic changes. These findings would suggest that R, combined with other sex hormones, may affect the structural integrity of the ligament and impact injury risk. Further study is needed to explore potential mechanisms for this association.