Polycystic ovary syndrome in relation to musculoskeletal health outcomes during midlife: a longitudinal cohort study

Research question: Is polycystic ovary syndrome (PCOS) associated with adverse musculoskeletal outcomes during the menopausal transition? Design: Parous women (n = 409) were enrolled from Project Viva, a prospective cohort study, and followed for 17 years. Women were classified as ‘diagnosed PCOS’ (n = 26) 3 years after enrolment; ‘probable PCOS’ (n = 41), based on the presence of two or more PCOS traits; and ‘no PCOS’ (n = 342). Musculoskeletal health outcomes were assessed by dual-energy X-ray absorptiometry, procollagen type I N-propeptide (P1NP) and C-terminal telopeptide of type I collagen [CTX-1] at a hospital visit at 17 years. Associations were evaluated using linear regressions. Results: At the mid-life visit, mean (SD) age was 51 (5) years, and 177 out of 409 (43%) women had reached menopause. Diagnosed and probable PCOS was associated with higher BMD at spine (0.05 [0.01, 0.09] g/cm²) and hip (0.05 [0.01, 0.08] g/cm²) but with lower CTX-1 (–13.7 [–23.7, –2.5] %) in age-adjusted analyses. After midlife whole-body fat mass adjustment, PCOS remained associated with spine (0.04 [0.00, 0.08] g/cm²) and hip BMD (0.04 [0.01, 0.07] g/cm²) and CTX-1 (–13.0 [–23.0, –1.8] %). Models adjusting for BMI versus fat mass showed similar results, although some confidence intervals included null values. When stratified by midlife menopausal status, PCOS was associated with spine (0.09 [0.02, 0.16] g/cm²) and hip (0.07 [0.02, 0.13] g/cm²) BMD only among post-menopausal women. Conclusions: PCOS is positively correlated to BMD (spine, hip) and inversely associated with bone turnover (CTX-1) in mid-life, independent of body fat, particularly after the menopause.