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Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies
Maki PM.. Menopause (New York, N.Y.), 2013-06-01
Topic: Risk, prevention and care in population studies
Objective The critical window hypothesis of hormone therapy (HT) and cognitive function states that the effects of HT depend on timing of initiation with respect to age, the menopausal transition, or both, and that optimal effects are evident with early initiation. This article reviews clinical studies that bear on this hypothesis. Methods Recognizing that the typical pattern of HT use is early HT initiation, this review describes findings from observational studies of ever use of HT and observational studies that looked specifically at the timing of HT on Alzheimer's disease (AD) and cognitive test performance. Randomized trials of HT and verbal memory are discussed, and neuroimaging studies bearing on the hypothesis are reviewed. Results Observational data suggest that HT generally reduces the risk of AD. Three of three observational studies that specifically examined the timing of initiation in relation to AD risk each provide support for the window, whereas three of five observational studies of HT timing and cognitive test performance do. Randomized clinical trials of estrogen therapy in younger women find support for the hypothesis. Conjugated equine estrogens/medroxyprogesterone acetate increases risks regardless of timing. Little is known about the cognitive effects of other combination HT formulations. Conclusions A definitive trial to test the critical window hypothesis is not feasible. Evidence drawn from other sources provides initial support for the hypothesis. Although these findings are relevant to women who use HT to treat vasomotor symptoms, HT is currently not indicated for the treatment of cognitive complaints or for dementia prevention.
Key findings
- Results Observational data suggest that HT generally reduces the risk of AD.
- Although these findings are relevant to women who use HT to treat vasomotor symptoms, HT is currently not indicated for the treatment of cognitive complaints or for dementia prevention.
Why it matters
This review of clinical studies reports that observational data suggest hormone therapy generally reduces Alzheimer's disease risk, but it states that hormone therapy is currently not indicated for treating cognitive complaints or preventing dementia. A definitive trial to test the critical window hypothesis is still needed.
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Study details
- Evidence strengthHigh
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, so that was left out: it earned 46 of the 96 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Menopause (New York, N.Y.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2013 — within 20 year(s) of the newest study here |
| 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 | 5 / 7 | Cited 243 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.2 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 15.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 63 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pauline M. Maki: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Illinois Chicago: institution h-index 918 (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 23715379) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 46 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 96 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1097/gme.0b013e3182960cf8
- PubMed: 23715379
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Maki, P. M. (2013). Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies. Menopause (New York, N.Y.). https://doi.org/10.1097/gme.0b013e3182960cf8
Vancouver
Maki PM. Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies. Menopause (New York, N.Y.). 2013. doi:10.1097/gme.0b013e3182960cf8. PMID: 23715379.
BibTeX
@article{maki2013-23715379,
author = {Maki, P. M.},
title = {{Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies}},
journal = {Menopause (New York, N.Y.)},
year = {2013},
doi = {10.1097/gme.0b013e3182960cf8},
pmid = {23715379},
url = {https://doi.org/10.1097/gme.0b013e3182960cf8}
}
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