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Estrogen replacement therapy and risk of Alzheimer disease
Paganini-Hill A, Henderson VW.. Archives of internal medicine, 1996-10-01
Topic: Amyloid, tau and blood-test diagnosis
Background With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. Objective To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. Study design and methods A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (+/- 1 year). Results The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (i.e., injections and/or creams) routes of administration. The risk decreased significantly with both increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). Conclusion This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.
Key findings
- Estrogen loss associated with menopause may contribute to the development of Alzheimer disease.
- Results The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88).
- The risk decreased significantly with both increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation.
- Conclusion This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.
Why it matters
In a nested case-control study of women from a Southern California retirement community, those who had used estrogen were less likely to have Alzheimer's or related dementia recorded on their death certificate (odds ratio 0.65, 95% CI 0.49–0.88). For oral conjugated equine estrogen, the odds fell further with higher doses and longer use (both P = .01). This is an observed association, not proof that estrogen prevents Alzheimer's; the authors concluded only that it "may be useful for preventing or delaying" the disease.
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Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of internal medicine) |
| Journal's citation record | 3 / 4 | Archives of Internal Medicine: journal h-index 462 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1996 — 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 | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 511 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 32 year(s) since 1996 |
| Impact for its field and year | 5 / 6 | Cited 23.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Annlia Paganini‐Hill: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Southern California: institution h-index 1,521 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8885820) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Paganini-Hill, A., & Henderson, V. W. (1996). Estrogen replacement therapy and risk of Alzheimer disease. Archives of internal medicine. https://doi.org/10.1001/archinte.1996.00440180075009
Vancouver
Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer disease. Archives of internal medicine. 1996. doi:10.1001/archinte.1996.00440180075009. PMID: 8885820.
BibTeX
@article{paganinihill1996-8885820,
author = {Paganini-Hill, A. and Henderson, V. W.},
title = {{Estrogen replacement therapy and risk of Alzheimer disease}},
journal = {Archives of internal medicine},
year = {1996},
doi = {10.1001/archinte.1996.00440180075009},
pmid = {8885820},
url = {https://doi.org/10.1001/archinte.1996.00440180075009}
}
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