Imagine your brain is a bustling metropolis, filled with busy roads and thriving businesses. Now, picture a superhero named Estrogen swooping in to save the day. Estrogen, like menopause hormone therapy (HT), has been studied for its potential to protect against Alzheimer’s disease (AD) and dementia. In this research, a systematic review and meta-analysis examined the effects of HT on AD and dementia risk. The findings showed that postmenopausal women aged 65 and older who used HT had an increased risk of dementia compared to those who used a placebo. However, when looking at observational studies, HT use was associated with a reduced risk of AD and all-cause dementia. Specifically, estrogen-only therapy (ET) showed protective effects, while estrogen-plus-progestogen therapy (EPT) did not. Interestingly, women who started ET in midlife had a 32% reduced risk of dementia. Late-life HT use showed increased risk but was not statistically significant. These results suggest that further research is needed to evaluate midlife estrogen therapy as a potential strategy for reducing AD risk. Curious to learn more? Check out the full article for all the details!

IntroductionDespite 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.MethodsOur 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.ResultsRandomized 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].DiscussionThese findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.

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