{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:58:53Z","timestamp":1791104333324,"version":"4.1.0"},"reference-count":49,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:p>Evidence from preclinical studies, randomized clinical trials (RCT), and observational studies underscores the importance of distinguishing among the different forms of estrogen and progestogens when evaluating the cognitive effects of hormone therapy (HT) in women. Despite this evidence, there is a lack of direct comparisons of different HT regimens. To provide insights into the effects of different HT formulations on cognition, this minireview focuses on RCT of verbal memory because evidence indicates that HT affects this cognitive domain more than others and because declines in verbal memory predict later development of Alzheimer's disease. Some observational studies indicate that estradiol confers benefits to verbal memory, whereas conjugated equine estrogens (CEE) confer risks. RCT to date show no negative impact of CEE on verbal memory, including the Women's Health Initiative Study of Cognitive Aging. Similarly, the Women's Health Initiative Memory Study showed no negative impact of CEE on dementia. Transdermal estradiol in younger postmenopausal women improved verbal memory in one small RCT but had no effect in another RCT. RCT of oral estradiol in younger and older postmenopausal women had neutral effects on cognitive function. In contrast, RCT show a negative impact of CEE plus medroxyprogesterone acetate on verbal memory in younger and older postmenopausal women. Small RCT show neutral or beneficial effects of other progestins on memory. Overall, RCT indicate that type of progestogen is a more important determinant of the effects of HT on memory than type of estrogen.<\/jats:p>","DOI":"10.1210\/en.2012-1175","type":"journal-article","created":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T22:56:00Z","timestamp":1339023360000},"page":"3564-3570","source":"Crossref","is-referenced-by-count":47,"title":["Minireview: Effects of Different HT Formulations on Cognition"],"prefix":"10.1210","volume":"153","author":[{"given":"Pauline M.","family":"Maki","sequence":"first","affiliation":[{"name":"Departments of Psychiatry and Psychology, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2012,6,6]]},"reference":[{"key":"2020071612131381700_B1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/jama.288.3.321","article-title":"Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.","volume":"288","author":"Rossouw","year":"2002","journal-title":"JAMA"},{"key":"2020071612131381700_B2","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1001\/jama.289.24.3243","article-title":"Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.","volume":"289","author":"Chlebowski","year":"2003","journal-title":"JAMA"},{"key":"2020071612131381700_B3","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1001\/jama.297.13.1465","article-title":"Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause.","volume":"297","author":"Rossouw","year":"2007","journal-title":"JAMA"},{"key":"2020071612131381700_B4","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1001\/jama.291.14.1701","article-title":"Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.","volume":"291","author":"Anderson","year":"2004","journal-title":"JAMA"},{"key":"2020071612131381700_B5","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1001\/jama.2011.382","article-title":"Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial.","volume":"305","author":"LaCroix","year":"2011","journal-title":"JAMA"},{"key":"2020071612131381700_B6","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.maturitas.2010.02.005","article-title":"Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials.","volume":"66","author":"Hogervorst","year":"2010","journal-title":"Maturitas"},{"key":"2020071612131381700_B7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/00042192-200007040-00008","article-title":"Memory functioning among midlife women: observations from the Seattle Midlife Women's Health Study.","volume":"7","author":"Woods","year":"2000","journal-title":"Menopause"},{"key":"2020071612131381700_B8","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1001\/archneur.1995.00540290075020","article-title":"The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort.","volume":"52","author":"Linn","year":"1995","journal-title":"Arch Neurol"},{"key":"2020071612131381700_B9","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1212\/01.WNL.0000163773.21794.0B","article-title":"Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years.","volume":"64","author":"Tierney","year":"2005","journal-title":"Neurology"},{"key":"2020071612131381700_B10","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1001\/archneur.64.6.862","article-title":"Neuropsychological measures in normal individuals that predict subsequent cognitive decline.","volume":"64","author":"Blacker","year":"2007","journal-title":"Arch Neurol"},{"key":"2020071612131381700_B11","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/WNN.0b013e3181a74ce7","article-title":"Aging, estrogens, and episodic memory in women.","volume":"22","author":"Henderson","year":"2009","journal-title":"Cogn Behav Neurol"},{"key":"2020071612131381700_B12","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1210\/jc.2009-1340","article-title":"Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy.","volume":"94","author":"Resnick","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612131381700_B13","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1210\/jc.2005-2097","article-title":"Effects of combination estrogen plus progestin hormone treatment on cognition and affect.","volume":"91","author":"Resnick","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612131381700_B14","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1001\/jama.289.20.2651","article-title":"Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.","volume":"289","author":"Shumaker","year":"2003","journal-title":"JAMA"},{"key":"2020071612131381700_B15","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1001\/jama.291.24.2947","article-title":"Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study.","volume":"291","author":"Shumaker","year":"2004","journal-title":"JAMA"},{"key":"2020071612131381700_B16","article-title":"California verbal learning test: research edition","author":"Delis","year":"1987"},{"key":"2020071612131381700_B17","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1176\/appi.ajp.158.2.227","article-title":"Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.","volume":"158","author":"Maki","year":"2001","journal-title":"Am J Psychiatry"},{"key":"2020071612131381700_B18","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1001\/jama.291.24.2959","article-title":"Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.","volume":"291","author":"Espeland","year":"2004","journal-title":"JAMA"},{"key":"2020071612131381700_B19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13697130500042417","article-title":"KEEPS: The Kronos Early Estrogen Prevention Study.","volume":"8","author":"Harman","year":"2005","journal-title":"Climacteric"},{"key":"2020071612131381700_B20","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1212\/01.wnl.0000277275.42504.93","article-title":"Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.","volume":"69","author":"Maki","year":"2007","journal-title":"Neurology"},{"key":"2020071612131381700_B21","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/gme.0b013e3181ace484","article-title":"Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.","volume":"16","author":"Maki","year":"2009","journal-title":"Menopause"},{"key":"2020071612131381700_B22","first-page":"238","article-title":"Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.","volume":"51","author":"Linzmayer","year":"2001","journal-title":"Arzneimittelforschung"},{"key":"2020071612131381700_B23","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/j.1447-0756.2010.01214.x","article-title":"Estrogen + progestin therapy and cognition: a randomized placebo-controlled double-blind study.","volume":"36","author":"Alhola","year":"2010","journal-title":"J Obstet Gynaecol Res"},{"key":"2020071612131381700_B24","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.psyneuen.2009.02.009","article-title":"A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women.","volume":"34","author":"Tierney","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"2020071612131381700_B25","doi-asserted-by":"crossref","first-page":"5782","DOI":"10.1210\/en.2010-0005","article-title":"Clinically relevant progestins regulate neurogenic and neuroprotective responses in vitro and in vivo.","volume":"151","author":"Liu","year":"2010","journal-title":"Endocrinology"},{"key":"2020071612131381700_B26","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1210\/en.2010-1061","article-title":"Medroxyprogesterone acetate antagonizes estrogen up-regulation of brain mitochondrial function.","volume":"152","author":"Irwin","year":"2011","journal-title":"Endocrinology"},{"key":"2020071612131381700_B27","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/00001756-200205070-00018","article-title":"Impact of progestins on estradiol potentiation of the glutamate calcium response.","volume":"13","author":"Nilsen","year":"2002","journal-title":"Neuroreport"},{"key":"2020071612131381700_B28","doi-asserted-by":"crossref","first-page":"10506","DOI":"10.1073\/pnas.1334098100","article-title":"Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling.","volume":"100","author":"Nilsen","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612131381700_B29","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1001\/archneur.63.7.945","article-title":"Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life.","volume":"63","author":"Yaffe","year":"2006","journal-title":"Arch Neurol"},{"key":"2020071612131381700_B30","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ajog.2004.08.017","article-title":"Estrogen therapy and risk of cognitive decline: results from the Women's Estrogen for Stroke Trial (WEST).","volume":"192","author":"Viscoli","year":"2005","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612131381700_B31","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neurobiolaging.2004.12.012","article-title":"A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life.","volume":"27","author":"Almeida","year":"2006","journal-title":"Neurobiol Aging"},{"key":"2020071612131381700_B32","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1532-5415.2007.01085.x","article-title":"The effect of 3-year treatment with 0.25 mg\/day of micronized 17\u03b2-estradiol on cognitive function in older postmenopausal women.","volume":"55","author":"Pefanco","year":"2007","journal-title":"J Am Geriatr Soc"},{"key":"2020071612131381700_B33","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0306-4530(92)90007-T","article-title":"Effects of estrogen on memory function in surgically menopausal women.","volume":"17","author":"Phillips","year":"1992","journal-title":"Psychoneuroendocrinology"},{"key":"2020071612131381700_B34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1185\/03007997609109322","article-title":"Replacement therapy and piperazine oestrone sulphate ('Harmogen') and its effect on memory.","volume":"4","author":"Hackman","year":"1976","journal-title":"Curr Med Res Opin"},{"key":"2020071612131381700_B35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/01.gme.0000189618.48774.7b","article-title":"Estrogen therapy selectively enhances prefrontal cognitive processes: a randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women.","volume":"13","author":"Joffe","year":"2006","journal-title":"Menopause"},{"key":"2020071612131381700_B36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/01.gme.0000230347.28616.1c","article-title":"Hot flashes and estrogen therapy do not influence cognition in early menopausal women.","volume":"14","author":"LeBlanc","year":"2007","journal-title":"Menopause"},{"key":"2020071612131381700_B37","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.psyneuen.2004.09.002","article-title":"Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women.","volume":"30","author":"Dunkin","year":"2005","journal-title":"Psychoneuroendocrinology"},{"key":"2020071612131381700_B38","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1212\/01.wnl.0000247277.81400.43","article-title":"Hormone effects on fMRI and cognitive measures of encoding: importance of hormone preparation.","volume":"67","author":"Gleason","year":"2006","journal-title":"Neurology"},{"key":"2020071612131381700_B39","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1097\/JGP.0b013e3181ff678a","article-title":"Differences in verbal memory performance in postmenopausal women receiving hormone therapy: 17\u03b2-estradiol versus conjugated equine estrogens.","volume":"19","author":"Wroolie","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"key":"2020071612131381700_B40","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.psyneuen.2010.08.002","article-title":"Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD.","volume":"36","author":"Silverman","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"2020071612131381700_B41","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1212\/WNL.0b013e3181c34b0c","article-title":"Characteristics of hormone therapy, cognitive function, and dementia: the prospective 3C Study.","volume":"73","author":"Ryan","year":"2009","journal-title":"Neurology"},{"key":"2020071612131381700_B42","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. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"2020071612131381700_B43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/JGP.0b013e3181beaaf4","article-title":"Effects of hormone therapy on depressive symptoms and cognitive functions in women with Alzheimer disease: a 12 month randomized, double-blind, placebo-controlled study of low-dose estradiol and norethisterone.","volume":"18","author":"Valen-Sendstad","year":"2010","journal-title":"Am J Geriatr Psychiatry"},{"key":"2020071612131381700_B44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1001\/jama.291.1.47","article-title":"National use of postmenopausal hormone therapy: annual trends and response to recent evidence.","volume":"291","author":"Hersh","year":"2004","journal-title":"JAMA"},{"key":"2020071612131381700_B45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/gme.0b013e3181f43404","article-title":"Trends in menopausal hormone therapy use of US office-based physicians, 2000\u20132009.","volume":"18","author":"Tsai","year":"2011","journal-title":"Menopause"},{"key":"2020071612131381700_B46","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/gme.0b013e31824b970a","article-title":"The 2012 hormone therapy position statement of: The North American Menopause Society.","volume":"19","year":"2012","journal-title":"Menopause"},{"key":"2020071612131381700_B47","doi-asserted-by":"crossref","first-page":"s1","DOI":"10.1210\/jc.2009-2509","article-title":"Postmenopausal hormone therapy: an Endocrine Society scientific statement.","volume":"95","author":"Santen","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612131381700_B48","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1212\/01.wnl.0000276984.19542.e6","article-title":"Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause.","volume":"69","author":"Rocca","year":"2007","journal-title":"Neurology"},{"key":"2020071612131381700_B49","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.maturitas.2009.08.003","article-title":"Premature menopause or early menopause: long-term health consequences.","volume":"65","author":"Shuster","year":"2010","journal-title":"Maturitas"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/8\/3564\/8978799\/endo3564.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/8\/3564\/8978799\/endo3564.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T15:33:13Z","timestamp":1594913593000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/153\/8\/3564\/2423827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,6]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2012-1175","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717097901.792452801","asserted-by":"object"}]},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,6]]}}}