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Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines
Open accessAbstract
The classic view of estrogen actions in the brain was confined to regulation of ovulation and reproductive behavior in the female of all mammalian species studied, including humans. Burgeoning evidence now documents profound effects of estrogens on learning, memory, and mood as well as neurodevelopmental and neurodegenerative processes. Most data derive from studies in females, but there is mounting recognition that estrogens play important roles in the male brain, where they can be generated from circulating testosterone by local aromatase enzymes or synthesized de novo by neurons and glia. Estrogen-based therapy therefore holds considerable promise for brain disorders that affect both men and women. However, as investigations are beginning to consider the role of estrogens in the male brain more carefully, it emerges that they have different, even opposite, effects as well as similar effects in male and female brains. This review focuses on these differences, including sex dimorphisms in the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration, and cognition, which, we argue, are due in a large part to sex differences in the organization of the underlying circuitry. There are notable sex differences in the incidence and manifestations of virtually all central nervous system disorders, including neurodegenerative disease (Parkinson's and Alzheimer's), drug abuse, anxiety, and depression. Understanding the cellular and molecular basis of sex differences in brain physiology and responses to estrogen and estrogen mimics is, therefore, vitally important for understanding the nature and origins of sex-specific pathological conditions and for designing novel hormone-based therapeutic agents that will have optimal effectiveness in men or women.
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“the HPA axis is influenced by sex hormones, particularly estrogen (Gillies and McArthur, 2010), which can modify stress responsiveness via its regulation of cortisol receptors (Oldehinkel and Bouma, 2011).”
From The effects of physical activity on cortisol and sleep: A systematic review and meta-analysis. (2022) · cites this paper as Gillies and McArthur, 2010
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Why is depression more prevalent in women?
Albert, P. R. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.150205 · Cited by 1,785
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Metadata
- Authors
- Gillies, G. E., & McArthur, S.
- Affiliations
- Hammersmith Hospital (GB)
- ORCID
- McArthur, Simon
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 62
- Issue
- 2
- Pages
- 155-198
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC2879914
- OpenAlex
- W2123640958
- Cited by
- 733
- References
- 506
- Citations by year
- 2026: 34 · 2025: 44 · 2024: 54 · 2023: 36 · 2022: 47 · 2021: 47 · 2020: 42 · 2019: 52 · 2018: 66 · 2017: 38 · 2016: 54 · 2015: 43 · 2014: 43 · 2013: 43 · 2012: 44
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (086871/Z/08/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- estrogen, estradiol, sex differences, brain, synaptic plasticity, neurodegeneration, brain development, learning and memory, mood, aromatase, testosterone, estrogen mimics, Parkinson's disease, Alzheimer's disease, drug abuse, anxiety, depression
- MeSH terms
- Alzheimer Disease, Animals, Brain, Brain Diseases, Estrogens, Female, Humans, Hypothalamus, Learning, Male, Memory, Parkinson Disease, Sex Factors, Rats
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