The Role of Estrogen in Brain and Cognitive Aging
Open accessAbstract
There are 3 common physiological estrogens, of which estradiol (E2) is seen to decline rapidly over the menopausal transition. This decline in E2 has been associated with a number of changes in the brain, including cognitive changes, effects on sleep, and effects on mood. These effects have been demonstrated in both rodent and non-human preclinical models. Furthermore, E2 interactions have been indicated in a number of neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. In normal brain aging, there are a number of systems that undergo changes and a number of these show interactions with E2, particularly the cholinergic system, the dopaminergic system, and mitochondrial function. E2 treatment has been shown to ameliorate some of the behavioral and morphological changes seen in preclinical models of menopause; however, in clinical populations, the effects of E2 treatment on cognitive changes after menopause are mixed. The future use of sex hormone treatment will likely focus on personalized or precision medicine for the prevention or treatment of cognitive disturbances during aging, with a better understanding of who may benefit from such treatment.
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E2 level quickly decreases throughout menopause.
“its level quickly decreases throughout menopause. 118”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [118]
E2 is the most active among the three physiological estrogens.
“among these estrogens, E2 is the most active”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [118]
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- Authors
- Russell, J. K., Jones, C. K., & Newhouse, P. A.
- Affiliations
- Vanderbilt University (US)
- VA Tennessee Valley Healthcare System (US)
- Corresponding author
- Newhouse, Paul A.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 16
- Issue
- 3
- Pages
- 649-665
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC6694379
- OpenAlex
- W2964886730
- Cited by
- 257
- References
- 226
- Citations by year
- 2026: 50 · 2025: 56 · 2024: 56 · 2023: 37 · 2022: 32 · 2021: 16 · 2020: 8 · 2019: 2
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG047992, 1R01AG054622)
- Alzheimer’s Association (PCTR-16-383171)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Keywords
- estrogen, estradiol, menopause, cognitive aging, brain aging, sex hormones, Alzheimer's disease, schizophrenia, depression, cholinergic system, dopaminergic system, mitochondrial function, sleep, mood, hormone replacement therapy, precision medicine
- MeSH terms
- Cognitive Aging, Animals, Brain, Estrogens, Humans
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