Relative Effects of Tamoxifen, Raloxifene, and Conjugated Equine Estrogens on Cognition
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OBJECTIVE: To compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years. METHODS: Annual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function in the two randomized placebo-controlled clinical trials of CEE therapies of the Women's Health Initiative Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential ethnic-related differences between studies, to Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with placebo therapy while controlling for differences between groups with respect to dementia risk factors. RESULTS: At baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was associated with a small mean relative deficit in 3MS scores of < or =0.5 units, which was fairly consistent between women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001) and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative deficits appeared to be greater among women with lower baseline 3MS scores: p = 0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE). CONCLUSIONS: Although unmeasured differences between trials may have confounded analyses, these findings raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women; however, the magnitude of the effect is small, and the long-term consequences are unknown.
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A subpopulation of TAM-treated patients experience cognitive disturbances such as confusion, deterioration of verbal memory, and executive dysfunction (often called "TAM brain fog").
“TAM, via unknown mechanisms, induces cognitive impairment in humans.”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [3]
The Discussion (page not available) reports possible small adverse effects of tamoxifen on global cognition, particularly among older women with lower baseline cognitive scores; it also cites studies suggesting memory effects. But the paper hedges the effect rather than establishing that tamoxifen induces impairment, and it does not identify confusion, executive dysfunction, or “TAM brain fog” as effects in a subpopulation of treated patients. (LLM, conf=0.87)
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- Authors
- Espeland, M. A., Shumaker, S. A., Limacher, M., Rapp, S. R., Bevers, T. B., Barad, D. H., Coker, L. H., Gaussoin, S. A., Stefanick, M. L., Lane, D. S., Maki, P. M., & Resnick, S. M.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of Florida (US)
- The University of Texas MD Anderson Cancer Center (US)
- Albert Einstein College of Medicine (US)
- Stanford University (US)
- Stony Brook Medicine (US)
- University of Illinois Chicago (US)
- National Institutes of Health (US)
- Corresponding author
- Espeland, Mark A.
- ORCID
- Venue
- Journal of Women's Health
- Publisher
- SAGE Publications
- Published
- 2010-03
- Volume
- 19
- Issue
- 3
- Pages
- 371-379
- ISSN
- 1059-7115 (ISSN-L)
- 1540-9996
- 1931-843X
- PMC
- PMC2867626
- OpenAlex
- W2015954236
- Cited by
- 30
- References
- 40
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 4 · 2015: 3 · 2014: 2 · 2013: 8 · 2012: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Women s Health (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services (U10-CA-37377, U10-CA-69974)
- Eli Lilly and Company
- AstraZeneca
- Women's Health Initiative
- Wake Forest University
- National Institutes of Health (N01 WH 44221, n01ag002106-019)
- National Institute on Aging (ZIAAG000190, N01-AG- 2106)
- National Heart, Lung, and Blood Institute
- National Cancer Institute (U10 CA 12027, U10-CA37377, U10CA069651, U10CA037377, U10CA069974, U10 CA 69651, U10CA012027, U10-CA-69974)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tamoxifen, raloxifene, conjugated equine estrogens, cognitive function, dementia risk, older women, hormone replacement therapy, selective estrogen receptor modulators, Women's Health Initiative Memory Study, Mini-Mental State Examination, hysterectomy
- MeSH terms
- Aged, Breast Neoplasms, Cognition, Estrogens, Conjugated (USP), Female, Humans, Middle Aged, Neuropsychological Tests, Risk Factors, Tamoxifen, Postmenopause, Selective Estrogen Receptor Modulators, Raloxifene Hydrochloride
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