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
Abstract
Context Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy. Objective To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo. Design, setting, and participants The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS. Intervention Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303). Main outcome measures Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment. Results The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (…
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The dynamics of sexually dimorphic hormones such as estrogen may affect different brain regions disproportionally.
“the dynamics of sexually dimorphic hormones such as estrogen [61–63] may affect different brain regions disproportionally.”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [61]
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- Authors
- Shumaker, S. A., Legault, C., Rapp, S. R., Thal, L., Wallace, R. B., Ockene, J. K., Hendrix, S. L., Jones III, B. N., Assaf, A. R., Jackson, R. D., Morley Kotchen, J., Wassertheil-Smoller, S., Wactawski-Wende, J., & for the WHIMS Investigators
- Affiliations
- Wake Forest University Health Sciences (US)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2003-05-28
- Volume
- 289
- Issue
- 20
- Pages
- 2651
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2131266318
- Cited by
- 2,178
- References
- 9
- Citations by year
- 2026: 53 · 2025: 58 · 2024: 73 · 2023: 55 · 2022: 55 · 2021: 57 · 2020: 45 · 2019: 49 · 2018: 49 · 2017: 60 · 2016: 52 · 2015: 72 · 2014: 67 · 2013: 72 · 2012: 92
- FWCI
- 137.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen plus progestin, hormone replacement therapy, dementia, mild cognitive impairment, Alzheimer's disease, postmenopausal women, Women's Health Initiative Memory Study, conjugated equine estrogens, medroxyprogesterone acetate, cognitive decline
- MeSH terms
- Aged, Cognition, Cognition Disorders, Dementia, Double-Blind Method, Estrogens, Conjugated (USP), Female, Humans, Neuropsychological Tests, Risk, Estrogen Replacement Therapy, Proportional Hazards Models, Medroxyprogesterone Acetate, Postmenopause, Progesterone Congeners
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