Age at menopause and chronic pain impact: an exploration of mediation using data from UK Biobank

Background Musculoskeletal symptoms are common during menopause transition, and early menopause is associated with the emergence of chronic pain. Exploring how menopause timing influences pain impact may enhance assessment, management, and support. Aim To explore the potential causal structure from age at menopause to severity of chronic pain, and to quantify mediation by depression, anxiety, sleep, BMI, and cognition. Method This is a historical cohort analysis within the UK Biobank baseline assessment (2006–2010) including postmenopausal participants with available exposure, mediator, outcome, and confounder data. Exposure was age at menopause (years); outcome was severity of chronic pain, defined as number of pain sites (NPS: 0–8 sites) with ≥3-month duration. We fitted Bayesian mediation models with a zero-inflated negative binomial likelihood. Models were adjusted for variables including age, ethnicity, deprivation, and hormone replacement therapy use. Results Among 94988 women, 55258 (58.2%) were postmenopausal with mean age at menopause 50.2 (± 4.6) years. Later menopause was associated with a direct 3% (95% credible interval:1%–5%) lower expected NPS and 1.2% (0.5% – 1.9%) increase per year in the odds of reporting zero sites. Later age at menopause was associated with fewer depressive symptoms resulting in 2.1% (1.6% – 2.7%) increase per year in the odds of reporting no pain. Anxiety, sleep, BMI, and cognition did not mediate the association. Conclusion Earlier menopause is associated with a greater impact of chronic pain in later life, potentially operating through depression, thus highlighting the importance of identifying and supporting women experiencing earlier menopause.