Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data.

Abstract

To investigate whether age at menopause is associated with the trajectory of multimorbidity progression. A retrospective cohort study. The UK Biobank. 121 017 postmenopausal women aged 40-69 years with complete baseline and menopausal data. Cox proportional hazards models were used to explore the associations between menopausal age and both multimorbidity and mortality. Multi-state models were further employed to evaluate the association of menopausal age with transitions from a health state to the first chronic disease (FCD), to multimorbidity, and to mortality from each state. Multimorbidity (defined as ≥ 2 of 35 chronic conditions) and mortality. Over a median follow-up period of 8.6 years, 86 821 women developed the FCD, 42237 multimorbidity, and 10 527 participants died. In the multi-state models analysis, from health to FCD, compared with women who experienced menopause after age 50 years, the risks increased by 32%, 14%, and 3% among women with premature, early, and relatively early menopause, respectively (HR = 1.32, 95% CI: 1.28-1.36; HR = 1.14, 95% CI: 1.11-1.17; HR = 1.03, 95% CI: 1.01-1.05). Similarly, for the transition from FCD to multimorbidity, the risks increased by 22% (HR = 1.22, 95% CI: 1.17-1.27), 13% (HR = 1.13, 95% CI: 1.09-1.16), and 6% (HR = 1.06, 95% CI: 1.03-1.08), respectively. Earlier menopause was associated with an increased risk of multimorbidity and mortality, mainly affecting two trajectories, from health to FCD and FCD to multimorbidity.