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Purpose of Review <p>To provide an updated integration of available data on the effects of menopause hormone therapy (MHT) on risk of Alzheimer’s disease (AD) and dementia.</p> Recent Findings <p>MHT’s impact on AD and dementia risk may be influenced by factors including timing of initiation, formulation, administration, and Apolipoprotein E epsilon 4 (APOE-4) status.</p> Summary <p>Randomized controlled trials of older postmenopausal women showed an increased risk of dementia with oral conjugated equine estrogen (CEEs) and medroxyprogesterone acetate (MPA) compared with placebo. In contrast, observational studies of midlife women tend to report more positive effects. This updated random effect meta-analysis of observational data indicates an 11.3% reduced risk of AD or dementia with overall MHT use [relative risk, RR = 0.887 (0.829-0.950),&#xa0;<i>P</i> = 0.006]. In meta-regression analysis, estrogen-only therapy, midlife use, and longer duration of use were associated with reduced dementia risk (<i>P</i> ≤ 0.004), while studies from Northern Europe were more likely to report an increased risk of dementia than other locations (<i>P</i> = 0.005). Sub-analyses showed an advantage of oral over transdermal estrogen, and non-significant associations of oral estrogen combined with progestogens. APOE-4 genotype influenced risk, with a 35.2% reduced risk of AD for non-carriers using MHT [RR = 0.648 (0.476-0.880), <i>P</i> = 0.006] and neutral effects for APOE-4 carriers [RR = 0.990 (0.751-1.305), <i>P</i> = 0.941]. These findings support evaluating precision MHT for AD risk reduction.</p>

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Systematic Review and Meta-analysis of Menopause Hormone Therapy (MHT) and the Risk of Alzheimer’s Disease and All-cause Dementia: Effects of MHT Characteristics, Location, and APOE-4 Status

  • 期刊论文

  • 发表日期：

    2025年1月16日

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  • Lisa Mosconi,
  • Caroline Andy,
  • Matilde Nerattini,
  • Trisha Ajila,
  • Camila Zarate,
  • Camila Boneu,
  • Francesca Fauci,
  • Michael Battista,
  • Silky Pahlajani,
  • Paul Christos,
  • Schantel Williams

摘要

Purpose of Review

To provide an updated integration of available data on the effects of menopause hormone therapy (MHT) on risk of Alzheimer’s disease (AD) and dementia.

Recent Findings

MHT’s impact on AD and dementia risk may be influenced by factors including timing of initiation, formulation, administration, and Apolipoprotein E epsilon 4 (APOE-4) status.

Summary

Randomized controlled trials of older postmenopausal women showed an increased risk of dementia with oral conjugated equine estrogen (CEEs) and medroxyprogesterone acetate (MPA) compared with placebo. In contrast, observational studies of midlife women tend to report more positive effects. This updated random effect meta-analysis of observational data indicates an 11.3% reduced risk of AD or dementia with overall MHT use [relative risk, RR = 0.887 (0.829-0.950), P = 0.006]. In meta-regression analysis, estrogen-only therapy, midlife use, and longer duration of use were associated with reduced dementia risk (P ≤ 0.004), while studies from Northern Europe were more likely to report an increased risk of dementia than other locations (P = 0.005). Sub-analyses showed an advantage of oral over transdermal estrogen, and non-significant associations of oral estrogen combined with progestogens. APOE-4 genotype influenced risk, with a 35.2% reduced risk of AD for non-carriers using MHT [RR = 0.648 (0.476-0.880), P = 0.006] and neutral effects for APOE-4 carriers [RR = 0.990 (0.751-1.305), P = 0.941]. These findings support evaluating precision MHT for AD risk reduction.