{"doi":"10.3389/fnagi.2023.1260427","title":"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.","journal":"Frontiers in Aging Neuroscience","year":2023,"id":316565,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":99,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":619918,"name":"Steven Jett","orcid":null,"position":1,"is_corresponding":false},{"id":734546,"name":"Caroline Andy","orcid":null,"position":2,"is_corresponding":false},{"id":994652,"name":"Caroline Carlton","orcid":null,"position":3,"is_corresponding":false},{"id":994651,"name":"Camila Zarate","orcid":null,"position":4,"is_corresponding":false},{"id":1020704,"name":"Camila Boneu","orcid":null,"position":5,"is_corresponding":false},{"id":744820,"name":"Michael T. Battista","orcid":"0000-0001-9090-6655","position":6,"is_corresponding":false},{"id":619156,"name":"Silky Pahlajani","orcid":"0000-0002-2510-9649","position":7,"is_corresponding":false},{"id":848766,"name":"Susan Loeb‐Zeitlin","orcid":null,"position":8,"is_corresponding":false},{"id":1020705,"name":"Yelena Havryulik","orcid":null,"position":9,"is_corresponding":false},{"id":994654,"name":"Schantel Williams","orcid":null,"position":10,"is_corresponding":false},{"id":305924,"name":"Paul J. Christos","orcid":"0000-0002-3211-9503","position":11,"is_corresponding":false},{"id":551993,"name":"Matthew E. Fink","orcid":"0000-0001-6649-3184","position":12,"is_corresponding":false},{"id":77490,"name":"Roberta Dı́az Brinton","orcid":"0000-0001-8450-772X","position":13,"is_corresponding":false},{"id":522063,"name":"Lisa Mosconi","orcid":"0000-0002-5093-8430","position":14,"is_corresponding":false},{"id":994650,"name":"Matilde Nerattini","orcid":null,"position":0,"is_corresponding":true}],"reference_count":204,"raw_metadata":null,"created_at":"2026-07-19T01:06:38.213358Z","pmid":"37937120","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}