{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:28:24Z","timestamp":1792171704170,"version":"4.4.0"},"reference-count":134,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"NIH\/NIA","award":["P01AG026572"],"award-info":[{"award-number":["P01AG026572"]}]},{"name":"Women's Alzheimer's Movement"},{"name":"the Luminescence Foundation"},{"name":"the Applebaum Foundation"},{"name":"philanthropic ort to the Weill Cornell Medicine Alzheimer's Prevention Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Accumulating evidence suggests that the effects of menopausal hormone therapy (MHT) on risk of Alzheimer disease (AD) and all-cause dementia are influenced by timing of initiation relative to age, time-since-menopause, and the type of formulation. Randomized clinical trials (RCTs) of MHT conducted in postmenopausal women ages 65 and older indicated an increased risk of dementia. While RCTs conducted in midlife are lacking, observational research has provided evidence for associations between midlife estrogen-only therapy (ET) use and a reduced risk of AD and dementia, whereas estrogen-progestogen therapy (EPT) was associated with more variable outcomes. However, existing studies are heterogenous, and conventional endpoints might not adequately assess MHT's potential for AD prevention. Herein, several approaches are being discussed, and the case is being made for utilizing AD biomarkers for assessment of early, AD-specific outcomes in relation to MHT use. From a clinical standpoint, findings that MHT may lower dementia risk warrant consideration as existing therapies like acetylcholinesterase inhibitors and memantine lack preventative efficacy, and vaccines for primary or secondary prevention are not yet available. MHT-associated risks, including breast cancer, stroke and venous thromboembolism, are generally considered rare (&amp;lt;10 events\/10 000 women). Overall, the literature supports renewed research interest in evaluating MHT as a female-specific, time-sensitive approach for AD risk reduction, which is key to applying cumulated data in clinical decision making concerning AD prevention.<\/jats:p>","DOI":"10.1210\/clinem\/dgaf026","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T03:00:11Z","timestamp":1736996411000},"page":"911-921","source":"Crossref","is-referenced-by-count":21,"title":["New Horizons in Menopause, Menopausal Hormone Therapy, and Alzheimer's Disease: Current Insights and Future Directions"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-8430","authenticated-orcid":false,"given":"Lisa","family":"Mosconi","sequence":"first","affiliation":[{"name":"Department of Neurology, Weill Cornell Medicine , New York, NY 10021 ,","place":["USA"]},{"name":"Department of Radiology, Weill Cornell Medicine , New York, NY 10021 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Nerattini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Cornell Medicine , New York, NY 10021 ,","place":["USA"]},{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence , Florence 50121 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schantel","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Cornell Medicine , New York, NY 10021 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Fink","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Cornell Medicine , New York, NY 10021 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"issue":"4","key":"2025031717092933600_dgaf026-B1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/alz.12638","article-title":"2022 Alzheimer's disease facts and figures","volume":"18","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"1","key":"2025031717092933600_dgaf026-B2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nrneurol.2012.241","article-title":"Preclinical Alzheimer disease-the challenges ahead","volume":"9","author":"Sperling","year":"2013","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"2025031717092933600_dgaf026-B3","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement"},{"issue":"6","key":"2025031717092933600_dgaf026-B4","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/ana.22628","article-title":"An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease","volume":"71","author":"Jack","year":"2012","journal-title":"Ann Neurol"},{"issue":"4","key":"2025031717092933600_dgaf026-B5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer's disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"issue":"4","key":"2025031717092933600_dgaf026-B6","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.3233\/JAD-2010-1337","article-title":"Early-versus late-onset Alzheimer's disease: more than age alone","volume":"19","author":"Koedam","year":"2010","journal-title":"J Alzheimers Dis"},{"issue":"7","key":"2025031717092933600_dgaf026-B7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrendo.2015.82","article-title":"Perimenopause as a neurological transition state","volume":"11","author":"Brinton","year":"2015","journal-title":"Nat Rev Endocrinol"},{"issue":"16","key":"2025031717092933600_dgaf026-B8","doi-asserted-by":"crossref","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. 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