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Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.


ABSTRACT:

Introduction

Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.

Methods

Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls). We used fixed and random effect meta-analysis to derive pooled relative risk (RR) and 95% confidence intervals (C.I.) from these studies.

Results

Randomized controlled trials conducted in postmenopausal women ages 65 and older show an increased risk of dementia with HT use compared with placebo [RR = 1.38, 95% C.I. 1.16-1.64, p < 0.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20-2.25, p = 0.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92-1.54, p = 0.18]. Conversely, observational studies indicate a reduced risk of AD [RR = 0.78, 95% C.I. 0.64-0.95, p = 0.013] and all-cause dementia [RR = .81, 95% C.I. 0.70-0.94, p = 0.007] with HT use, with protective effects noted with ET [RR = 0.86, 95% C.I. 0.77-0.95, p = 0.002] but not with EPT [RR = 0.910, 95% C.I. 0.775-1.069, p = 0.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513-0.915, p = 0.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474-1.266, p = 0.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979-1.789, p = 0.069; ET: RR = 1.066, 95% C.I. 0.996-1.140, p = 0.066].

Discussion

These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.

SUBMITTER: Nerattini M 

PROVIDER: S-EPMC10625913 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.

Nerattini Matilde M   Jett Steven S   Andy Caroline C   Carlton Caroline C   Zarate Camila C   Boneu Camila C   Battista Michael M   Pahlajani Silky S   Loeb-Zeitlin Susan S   Havryulik Yelena Y   Williams Schantel S   Christos Paul P   Fink Matthew M   Brinton Roberta Diaz RD   Mosconi Lisa L  

Frontiers in aging neuroscience 20231023


<h4>Introduction</h4>Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer's disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.<h4>Methods</h4>Our systematic search yielded 6 RCT reports (21,065 treated and 20,997 placebo participants) and 45 observational reports (768,866 patient cases and 5.5 million controls  ...[more]

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