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Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial
Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, McCleary CA, Klein RA et al.. Neurology, 2000-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Methods Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Results Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Conclusion Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Henderson, V. W., Paganini-Hill, A., Miller, B. L., Elble, R. J., Reyes, P. F., Shoupe, D., et al. (2000). Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial. Neurology. https://doi.org/10.1212/wnl.54.2.295
Vancouver
Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, et al. Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial. Neurology. 2000. doi:10.1212/wnl.54.2.295. PMID: 10668686.
BibTeX
@article{henderson2000-10668686,
author = {Henderson, V. W. and Paganini-Hill, A. and Miller, B. L. and Elble, R. J. and Reyes, P. F. and Shoupe, D. and McCleary, C. A. and Klein, R. A. and others},
title = {{Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial}},
journal = {Neurology},
year = {2000},
doi = {10.1212/wnl.54.2.295},
pmid = {10668686},
url = {https://doi.org/10.1212/wnl.54.2.295}
}
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Key findings
- Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder.
- Results Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks.
- At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status.
- Conclusion Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD.
- These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.
Why it matters
In this randomized, double-blind, placebo-controlled trial of 42 women with mild-to-moderate Alzheimer's disease dementia, short-term conjugated equine estrogens showed no significant differences or statistical trends versus placebo on the primary cognitive outcome, clinician-rated global impression of change, or caregiver-rated functional status. The authors conclude that short-term estrogen therapy does not improve symptoms of most women with Alzheimer's disease, while noting the small sample size limits conclusions.
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Study details
- Evidence strengthHigh
How this study scored 74/100
Published in a leading specialty journal, and it is a randomized controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2000 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomized / blinded | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 551 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.7 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 6 / 6 | Cited 54.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Martin Rhys Farlow: h-index 118 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10668686) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 74 / 100 | — |
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