| Title: | Hormone replacement therapy and dementia risk among postmenopausal women: Identifying responsive subgroups in the UK Biobank |
| Journal: | Alzheimer's & Dementia |
| Published: | 26 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42644405/ |
| DOI: | https://doi.org/10.1002/alz.71679 |
Publication 20887
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Abstract
INTRODUCTION: Modifiers of the association between hormone replacement therapy (HRT) use and dementia risk and responsive subgroups, are unknown.</p>
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.</p>
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.</p>
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.</p>
14 Keywords
- Aged
- Apolipoprotein E4
- Biological Specimen Banks
- Dementia
- Estrogen Replacement Therapy
- Estrogens
- Female
- Hormone Replacement Therapy
- Humans
- Middle Aged
- Postmenopause
- Risk Factors
- UK Biobank
- United Kingdom
9 Authors
- Steven Squires
- Rasha NM Saleh
- Luke C Pilling
- Janice L Atkins
- Janice M Ranson
- Xin You Tai
- David Vauzour
- David J Llewellyn
- Anne-Marie Minihane
1 Application
| Application ID | Title |
|---|---|
| 14631 | Genetic and environmental influences on ageing well |
Enabling scientific discoveries that improve human health