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80/100

✓ Peer-reviewed alzhub usefulness score 80 out of 100. How common it is

Reviewed as evidence on: Menopause timing / hormone therapy (estrogen-only) and dementia risk and AD neuropathology 7 studies (what the news said). Being listed means the study bears on the question, not that it agrees with the news.

Topic: Risk, prevention and care in population studies

Context The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population. Objectives To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA). Design, setting, and participants A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004. Interventions Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421). Main outcome measure Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE). Results During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P 2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07). Conclusion For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.

Key findings

Results During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04).

Why it matters

In a randomized, placebo-controlled trial of 2,808 women aged 65–79 who had had a hysterectomy, those given daily conjugated equine estrogen scored 0.26 points lower on average on a global thinking test (3MSE) than those on placebo over about 5.4 years. The study concluded that, for women 65 or older, "hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment." It measured test scores, not Alzheimer's diagnoses, and does not show how estrogen affects younger women.

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Study details

Participants1,387
Effect size92.1%; 95.3%
Evidence strengthHigh

How this study scored 80/100

Published in a top-tier journal, and it is a randomised controlled trial.

Component	Points	Why
Journal tier	10 / 10	Tier 1 — top-tier general journal (JAMA)
Journal's citation record	4 / 4	JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29)
Study design	11 / 12	A randomised 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	2004 — older than 20 years, still counted
Sample size	3 / 4	1,387 participants
Effect reported	2 / 3	Effect reported as a number, without an interval or test
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	2 / 2	Randomised and blinded or placebo-controlled (as stated in the record)
Times cited	6 / 7	Cited 796 times (OpenAlex, 2026-10-10)
Citations per year	4 / 5	33.2 citations a year over 24 year(s) since 2004
Impact for its field and year	6 / 6	Cited 41.3× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 16 other studies in this library
Still being cited	3 / 4	Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Mark Andrew Espeland: h-index 90 (OpenAlex, whole career)
Institution's track record	1 / 3	Wake Forest University: institution h-index 835 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 15213207)
Free to read	0 / 2	Behind a paywall — scores zero
Total	80 / 100	—

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Cite this study APA, Vancouver, BibTeX · download .bib or .ris

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APA 7th

Espeland, M. A., Rapp, SR., Shumaker, S. A., Brunner, R., Manson, J. E., Sherwin, B. B., et al. (2004). Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. https://doi.org/10.1001/jama.291.24.2959

Vancouver

Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004. doi:10.1001/jama.291.24.2959. PMID: 15213207.

BibTeX

@article{espeland2004-15213207,
  author  = {Espeland, M. A. and Rapp, SR. and Shumaker, S. A. and Brunner, R. and Manson, J. E. and Sherwin, B. B. and Hsia, J. and Margolis, K. L. and others},
  title   = {{Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study}},
  journal = {JAMA},
  year    = {2004},
  doi     = {10.1001/jama.291.24.2959},
  pmid    = {15213207},
  url     = {https://doi.org/10.1001/jama.291.24.2959}
}

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