{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:29:28Z","timestamp":1794029368766,"version":"4.8.0"},"reference-count":201,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Despite a large preclinical literature demonstrating neuroprotective effects of estrogen, use of menopausal hormone therapy (HT) for Alzheimer\u2019s disease (AD) risk reduction has been controversial. Herein, we conducted a systematic review and meta-analysis of HT effects on AD and dementia risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20131.64, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001], driven by estrogen-plus-progestogen therapy (EPT) [RR = 1.64, 95% C.I. 1.20\u20132.25, <jats:italic>p<\/jats:italic>\u2009=\u20090.002] and no significant effects of estrogen-only therapy (ET) [RR = 1.19, 95% C.I. 0.92\u20131.54, <jats:italic>p<\/jats:italic>\u2009=\u20090.18]. Conversely, observational studies indicate a reduced risk of AD [RR\u2009= 0.78, 95% C.I. 0.64\u20130.95, <jats:italic>p<\/jats:italic>\u2009=\u20090.013] and all-cause dementia [RR\u2009=\u2009.81, 95% C.I. 0.70\u20130.94, <jats:italic>p<\/jats:italic>\u2009=\u20090.007] with HT use, with protective effects noted with ET [RR\u2009=\u20090.86, 95% C.I. 0.77\u20130.95, <jats:italic>p<\/jats:italic>\u2009=\u20090.002] but not with EPT [RR\u2009= 0.910, 95% C.I. 0.775\u20131.069, <jats:italic>p<\/jats:italic>\u2009=\u20090.251]. Stratified analysis of pooled estimates indicates a 32% reduced risk of dementia with midlife ET [RR = 0.685, 95% C.I. 0.513\u20130.915, <jats:italic>p<\/jats:italic>\u2009=\u20090.010] and non-significant reductions with midlife EPT [RR = 0.775, 95% C.I. 0.474\u20131.266, <jats:italic>p<\/jats:italic>\u2009=\u20090.309]. Late-life HT use was associated with increased risk, albeit not significant [EPT: RR = 1.323, 95% C.I. 0.979\u20131.789, <jats:italic>p<\/jats:italic>\u2009=\u20090.069; ET: RR = 1.066, 95% C.I. 0.996\u20131.140, <jats:italic>p<\/jats:italic>\u2009=\u20090.066].<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings support renewed research interest in evaluating midlife estrogen therapy for AD risk reduction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2023.1260427","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T07:14:51Z","timestamp":1698045291000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":116,"title":["Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer\u2019s disease and dementia"],"prefix":"10.3389","volume":"15","author":[{"given":"Matilde","family":"Nerattini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Jett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Andy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Carlton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Zarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Boneu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Battista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silky","family":"Pahlajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Loeb-Zeitlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Havryulik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schantel","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Christos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Diaz","family":"Brinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mosconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2017.03.033","article-title":"Estrogen enhances hippocampal gray-matter volume in young and older postmenopausal women: a prospective dose-response study","volume":"56","author":"Albert","year":"2017","journal-title":"Neurobiol. 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Epidemiol."},{"key":"ref19","volume-title":"Hormone replacement therapy: Knowledge and use in the United States","author":"Brett","year":"2001"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1196\/annals.1347.005","article-title":"Investigative models for determining hormone therapy-induced outcomes in brain: evidence in support of a healthy cell bias of estrogen action","volume":"1052","author":"Brinton","year":"2005","journal-title":"Ann. N. Y. Acad. 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Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1089\/jwh.2012.3789","article-title":"Sex and gender differences in Alzheimer's disease: recommendations for future research","volume":"21","author":"Carter","year":"2012","journal-title":"J Womens Health (Larchmt)"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5303","DOI":"10.1210\/en.2006-0495","article-title":"Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neurons: therapeutic implications","volume":"147","author":"Chen","year":"2006","journal-title":"Endocrinology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1037\/a0032968","article-title":"Modeling dependent effect sizes with three-level meta-analyses: a structural equation modeling approach","volume":"19","author":"Cheung","year":"2014","journal-title":"Psychol. 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Psychiatry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1001\/jamaneurol.2023.0455","article-title":"Association of age at menopause and hormone therapy use with tau and beta-amyloid positron emission tomography","volume":"80","author":"Coughlan","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1002\/alz.12759","article-title":"Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease","volume":"19","author":"Depypere","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"Dersimonian","year":"1986","journal-title":"Control. Clin. Trials"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e79977","DOI":"10.1371\/journal.pone.0079977","article-title":"Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention","volume":"8","author":"Ding","year":"2013","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.0006-341X.2000.00455.x","article-title":"Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis","volume":"56","author":"Duval","year":"2000","journal-title":"Biometrics"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1212\/WNL.55.6.875","article-title":"Effect of estrogen on cerebral glucose metabolism in postmenopausal women","volume":"55","author":"Eberling","year":"2000","journal-title":"Neurology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/S0197-4580(02)00056-8","article-title":"Preliminary evidence that estrogen protects against age-related hippocampal atrophy","volume":"24","author":"Eberling","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.neurobiolaging.2004.11.009","article-title":"Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy","volume":"26","author":"Erickson","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1037\/a0017292","article-title":"A cross-sectional study of hormone treatment and hippocampal volume in postmenopausal women: evidence for a limited window of opportunity","volume":"24","author":"Erickson","year":"2010","journal-title":"Neuropsychology"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.2337\/dc15-1385","article-title":"Impact of type 2 diabetes and postmenopausal hormone therapy on incidence of cognitive impairment in older women","volume":"38","author":"Espeland","year":"2015","journal-title":"Diabetes Care"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1001\/jamainternmed.2013.7727","article-title":"Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years","volume":"173","author":"Espeland","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"CD004143","DOI":"10.1002\/14651858.CD004143.pub2","article-title":"Long term hormone therapy for perimenopausal and postmenopausal women","volume":"20","author":"Farquhar","year":"2005","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"CD004143","DOI":"10.1002\/14651858.CD004143.pub3","article-title":"Long term hormone therapy for perimenopausal and postmenopausal women","volume":"15","author":"Farquhar","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease Meta analysis consortium","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41582-018-0032-9","article-title":"Sex differences in Alzheimer disease - the gateway to precision medicine","volume":"14","author":"Ferretti","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1001\/archpsyc.55.9.809","article-title":"The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis","volume":"55","author":"Gao","year":"1998","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e2005","DOI":"10.1212\/WNL.0000000000007326","article-title":"Reproductive period and risk of dementia in a diverse cohort of health care members","volume":"92","author":"Gilsanz","year":"2019","journal-title":"Neurology"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e1001833","DOI":"10.1371\/journal.pmed.1001833","article-title":"Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-cognitive and affective study","volume":"12","author":"Gleason","year":"2015","journal-title":"PLoS Med."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1046\/j.1471-4159.1996.66051836.x","article-title":"Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons","volume":"66","author":"Goodman","year":"1996","journal-title":"J. Neurochem."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1002\/ana.410280607","article-title":"A case-control study of Alzheimer's disease","volume":"28","author":"Graves","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.pscychresns.2006.01.001","article-title":"Differences in brain volumes among males and female hormone-therapy users and nonusers","volume":"147","author":"Greenberg","year":"2006","journal-title":"Psychiatry Res."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1152\/physrev.00036.2014","article-title":"Estrogen effects on cognitive and synaptic health over the lifecourse","volume":"95","author":"Hara","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1212\/WNL.52.3.551","article-title":"A cross-ethnic analysis of risk factors for AD in white Hispanics and white non-Hispanics","volume":"52","author":"Harwood","year":"1999","journal-title":"Neurology"},{"key":"ref57","volume-title":"Statistical methods for meta-analysis","author":"Hedges","year":"1985"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1136\/jnnp.2003.024927","article-title":"Postmenopausal hormone therapy and Alzheimer\u2019s disease risk: interaction with age","volume":"76","author":"Henderson","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref59","first-page":"A205","article-title":"Prior use of hormone therapy and incident Alzheimer\u2019s disease in the Women\u2019s health Initiative memory study","volume":"68","author":"Henderson","year":"2007","journal-title":"Neurology"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1001\/archneur.1994.00540210068014","article-title":"Estrogen replacement therapy in older women: comparisons between Alzheimer's disease cases and nondemented control subjects","volume":"51","author":"Henderson","year":"1994","journal-title":"Arch. Neurol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1212\/WNL.0b013e318271f88f","article-title":"Estrogens and Alzheimer disease risk: is there a window of opportunity?","volume":"79","author":"Henderson","year":"2012","journal-title":"Neurology"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/ana.410150406","article-title":"Alzheimer's disease: a study of epidemiological aspects","volume":"15","author":"Heyman","year":"1984","journal-title":"Ann. Neurol."},{"key":"ref63","article-title":"Including variants on randomized trials","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Higgins Jpt","year":"2022"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat. Med."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1056\/NEJMoa1505241","article-title":"Vascular effects of early versus late postmenopausal treatment with estradiol","volume":"374","author":"Hodis","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/GME.0000000000000343","article-title":"Methods and baseline cardiovascular data from the early versus late intervention trial with estradiol testing the menopausal hormone timing hypothesis","volume":"22","author":"Hodis","year":"2015","journal-title":"Menopause"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S0306-4522(00)00410-3","article-title":"The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis","volume":"101","author":"Hogervorst","year":"2000","journal-title":"Neuroscience"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.maturitas.2017.01.002","article-title":"Risk of Alzheimer's disease among users of postmenopausal hormone therapy: a nationwide case-control study","volume":"98","author":"Imtiaz","year":"","journal-title":"Maturitas"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1212\/WNL.0000000000003696","article-title":"Postmenopausal hormone therapy and Alzheimer disease: a prospective cohort study","volume":"88","author":"Imtiaz","year":"","journal-title":"Neurology"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3233\/JAD-140336","article-title":"Oophorectomy, hysterectomy, and risk of Alzheimer's disease: a nationwide case-control study","volume":"42","author":"Imtiaz","year":"2014","journal-title":"J. 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