Premature menopause and risk of neurological disease: Basic mechanisms and clinical implications
Open accessAbstract
Since basic scientific studies in the 1990s revealed dramatic gender differences in neurological damage from cerebral ischemia, significant evidence has accumulated for a neuroprotective role of ovarian-derived 17β-Estradiol (E2). Intriguingly, observational studies have further suggested that early and prolonged loss of ovarian E2 (premature menopause) leads to a doubled lifetime risk for dementia and a fivefold increased risk of mortality from neurological disorders, but some controversy remains. Here, we briefly summarize and analyze clinical cohort studies assessing the detrimental neurological outcomes of premature menopause. Furthermore, we discuss current basic science studies elucidating the molecular mechanisms underlying the enhanced risk of neurological disease in prematurely menopausal women and the "window of opportunity" for estrogen benefit. Finally, we highlight four critical issues in the field that require collaboration between basic scientists and clinicians for successful resolution, with the ultimate goal of maintaining optimal neurological health in prematurely menopausal women.
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In animal experiments, bilaterally ovariectomized rats developed Aβ 1−42 in the hippocampus after exposure to stress.
“In animal experiments, bilaterally ovariectomized rats developed Aβ 1 −42 in the hippocampus after exposure to stress, a finding which corroborate with our finding of more Aβ in women with surgical menopause at young ages [59,66].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [59]
Section 3.1 reports increased hippocampal amyloidogenesis in surgically menopausal rats after ischemic stress. It separately says their hippocampus was more sensitive to the neurotoxic effects of Aβ1-42; it does not establish that the stress caused the rats to develop that specific peptide. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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Cites
Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women
Bove, R., Secor, E., Chibnik, L. B., Barnes, L. L., Schneider, J. A., Bennett, D. A., & De Jager, P. L. (2014) · Neurology · doi:10.1212/wnl.0000000000000033 · Cited by 437 · see citing works
Premature menopause or early menopause and risk of ischemic stroke
Rocca, W. A., Grossardt, B. R., Miller, V. M., Shuster, L. T., & Brown, R. D. (2012) · Menopause · doi:10.1097/gme.0b013e31822a9937 · Cited by 188 · cited 2× · see citing works
“Likewise, the increased risk of stroke, cardiovascular disease and all-cause mortality observed in premenopausally oophorectomized women was not observed in those who initiated early ET (Parker, 2013; Parker et al., 2013; Rocca et al., 2012a).”
BackgroundHysterectomy, Oophorectomy, Estrogen, and the Risk of Dementia
Rocca, W. A., Grossardt, B. R., Shuster, L. T., & Stewart, E. A. (2012) · Neurodegenerative Diseases · doi:10.1159/000334764 · Cited by 122 · see citing works
Zhang, Q.-G., Wang, R.-M., Scott, E., Han, D., Dong, Y., Tu, J.-Y., Yang, F., Reddy Sareddy, G., Vadlamudi, R. K., & Brann, D. W. (2013) · Brain · doi:10.1093/brain/awt046 · Cited by 50 · see citing works
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Cited by
Sorted by citations
Sex differences in Alzheimer’s disease and common neuropathologies of aging
Oveisgharan, S., Arvanitakis, Z., Yu, L., Farfel, J., Schneider, J. A., & Bennett, D. A. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1920-1 · Cited by 330 · see citing works
- Authors
- Scott, E. L., Zhang, Q.-G., Vadlamudi, R. K., & Brann, D. W.
- Affiliations
- University System of Georgia (US)
- Augusta University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Brann, Darrell W.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 389
- Issue
- 1-2
- Pages
- 2-6
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC4040297
- OpenAlex
- W1972366842
- Cited by
- 36
- References
- 4
- Citations by year
- 2026: 3 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institute of Neurological Disorders and Stroke (NS050730, R01NS050730)
- 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
- premature menopause, estradiol, neuroprotection, dementia risk, cerebral ischemia, sex differences in neurodegeneration, ovarian estrogen, window of opportunity, estrogen replacement therapy
- MeSH terms
- Estrogens, Female, Humans, Menopause, Premature, Nervous System Diseases, Risk, Cohort Studies, Women's Health
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