Hormone replacement therapy and dementia risk among postmenopausal women: Identifying responsive subgroups in the UK Biobank.

INTRODUCTION

Modifiers of the association between hormone replacement therapy (HRT) use and dementia risk and responsive subgroups, are unknown.

METHODS

In 183,450 postmenopausal women from the UK Biobank (mean 13.3 years follow-up), multivariable Cox regression models evaluated associations between HRT use (≥1 year) and all-cause dementia and dementia subtypes. Stratified analyzes assessed modification by menopause type, lifetime estrogen exposure, apolipoprotein E (APOE) ɛ4 genotype, and age at HRT initiation.

RESULTS

Over 2.43 million person-years, 3,948 dementia cases were identified. HRT use was associated with lower all-cause dementia (hazard ratio [HR] 0.90; 95% CI, 0.84-0.96), with stronger associations in surgical menopause (0.74, 0.65-0.84), APOE ɛ4 carriers (0.87, 0.80-0.95) and women with lower endogenous estrogen exposure (0.84, 0.77-0.93). Initiation between ages 46 and 56 conferred the greatest benefit.

DISCUSSION: HRT use was associated with lower dementia risk, and these findings may help inform more tailored approaches to HRT prescribing in relation to women's lifetime dementia risk.