Evidence map›Paper›PMID 26109339›Full record

ReviewPhysiological reviews2015

Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse.

Yuko Hara, Elizabeth M Waters, Bruce S McEwen, John H Morrison

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Physiological reviews, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed, 6 pooled it
22.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

262 citing papers in PubMed, 6 syntheses or guidelines pooled it, 449 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Menstrual cycle phase affects alcohol impairment of working memory.Alcohol, clinical & experimental research · 2025
    Trial
  9. Trial
  10. Trial
  11. Article
  12. Article
  13. Article
  14. Article
  15. Hormone replacement therapy and its association with LATE-NC in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  16. Interaction of diet and physical activity on dementia risk: the Rotterdam study.The journal of prevention of Alzheimer's disease · 2026
    Article
  17. Age at menopause,Research square · 2026
    Article
  18. Cancer treatment-related cognitive impairment.Neuro-oncology advances · 2026
    Review
  19. Causal effects of reproductive traits on cognitive function: A two-sample and multivariable mendelian randomization study.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
    Article
  20. Article

202 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Yuko HaraFishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York.
Elizabeth M WatersFishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York.
Bruce S McEwenFishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York.
John H MorrisonFishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Department of Geriatrics and Palliative Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; and Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York.
Icahn School of Medicine at Mount Sinai · USRockefeller University · US

Funding

The Nonhuman Primate CoreP01AG016765 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI MORRISON, JOHN H. · 1999 to 2016
$26.1M
Glutamate receptors in aging cortical circuitsR37AG006647 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MORRISON, JOHN H · 2007 to 2015
$4.8M
NIA NIH HHS P01 AG016765NIA NIH HHS P01 AG16765NIA NIH HHS R37 AG006647NIA NIH HHS R37 AG06647
6 · The paper itself

Abstract

Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.

Indexed as

CognitionSynaptic TransmissionAge FactorsAgingAnimalsBrainCognition DisordersEstrogensFemaleHumansMaleMenopauseProgesteroneReceptors, EstrogenSynapsesEstrogensProgesteroneReceptors, Estrogen

Identifiers

PMID26109339
PMCPMC4491541
OpenAlexW2203314189

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.