Associations between endogenous sex hormones and multisite chronic musculoskeletal pain

Background: Sex-differences in pain perception have been documented; however, the role of sex hormones in chronic musculoskeletal pain (CMP) remains unclear. Therefore, this study investigated whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CMP. Methods: We utilised data from the UK Biobank (n=357 424; females: 51.6%; white: 95.2%). Serum concentrations of oestradiol (E2), testosterone (T), and SHBG were measured at baseline. Chronic pain (≥3 months) in the neck/shoulder, back, hip, knee, or ‘all over the body’ was assessed at baseline and three follow-ups. Mixed-effects multinomial/logistic regression models were used. Results: In multivariable analyses, greater concentrations of T and T/SHBG were associated with a lower number of CMP sites in both males (T: relative risk ratio=0.81 per standard deviation, 95% confidence interval [0.77–0.86] and T/SHBG: 0.85 [0.80–0.92]) and females (T: 0.85 [0.81–0.89] and T/SHBG: 0.93 [0.89–0.97] [all P-values for trend ≤0.001]). Greater T concentrations and T/SHBG were also associated with lower odds of CMP across all sites, while higher concentrations of SHBG were associated with lower odds of neck/shoulder CMP in both sexes. There was no association between concentrations of E2, SHBG, or E2/SHBG and number of CMP or site-specific CMP in either sex. Conclusion: In both sexes, greater T concentrations and T/SHBG were associated with lower number of CMP sites and site-specific CMP, while greater concentrations of SHBG were linked to lower odds of neck/shoulder CMP. These findings suggest a potential involvement of sex steroids in the pathogenesis of CMP and underscore the need for further investigation into their potential in chronic pain management strategies.