Cited by 188Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsAcute Ischemic Stroke Management

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Premature menopause or early menopause and risk of ischemic stroke

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Rocca, Walter A., Grossardt, Brandon R., Miller, Virginia M., Shuster, Lynne T., Brown, Robert D.·2012·Menopause

DOI 10.1097/gme.0b013e31822a9937PMC PMC3258468

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Abstract

In Brief Objective The general consensus has been that estrogen is invariably a risk factor for ischemic stroke (IS). We reviewed new observational studies that challenge this simple conclusion. Methods This was a review of observational studies of the association of premature or early menopause with stroke or IS published in English from 2006 through 2010. Results Three cohort studies showed an increased risk of all types of stroke in women who underwent bilateral oophorectomy compared with women who conserved their ovaries before age 50 years. The increased risk of stroke was reduced by hormone therapy in one of the studies, suggesting that estrogen deprivation is involved in the association. Four additional observational studies showed an association of all types of stroke or IS with the early onset of menopause or with a shorter life span of ovarian activity. In three of the seven studies, the association was restricted to IS. Age at menopause was more important than type of menopause (natural vs induced). Conclusions The findings from seven recent observational studies challenge the consensus that estrogen is invariably a risk factor for IS and can be reconciled by a unifying timing hypothesis. We hypothesize that estrogen is protective for IS before age 50 years and may become a risk factor for IS after age 50 years or, possibly, after age 60 years. These findings are relevant to women who experienced premature or early menopause or to women considering prophylactic bilateral oophorectomy before the onset of natural menopause. The findings from seven recent observational studies challenge the consensus that estrogen is invariably a risk factor of ischemic stroke. In this study, a unifying theory is proposed, in which estrogen is protective before approximately age 50 years and may become a risk factor of ischemic stroke after age 50 years or, possibly, after age 60 years.

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Additional file 1 of Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study
Li, Y., Zhao, D., Wang, M., Sun, J.-Y., Liu, J., Qi, Y., Hao, Y.-C., Deng, Q.-J., Liu, J., Liu, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14100526
Management of surgical menopause in female patients with bladder cancer undergoing radical cystectomy
Day, E., Bizzarri, F. P., Mackenzie, C., Szabados, B. E., Nelson, A. W., Colquhoun, A., Perry, M. J. A., Kelly, J. D., & Lobo, N. (2026) · Nature Reviews Urology · doi:10.1038/s41585-026-01124-z
“The association between surgical menopause and neurological disorders remains poorly defined, as available evidence is limited to retrospective observational studies 35,36 .”
Self-reported early-onset menopause among women living with HIV and hypertension in Botswana: a cross-sectional study
Molefe‐Baikai, O. J., Kebotsamang, K., Manyeagae, G. D., Moshomo, T., Mawi, M., Mogaetsho, E., Gaolathe, T., Molebatsi, K., Kelepile, M., Kgotlaetsile, K., et al. (2026) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000002760
“Although early menopause is generally associated with higher long-term cardiometabolic risk, 10,11 in our study, women with early-onset menopause had similar (and in some cases) lower prevalence of comorbidities compared with those with regular menopause; though these differences were not…”
The epidemiology of menopause
Karvonen-Gutierrez, C. A., Gold, E. B., Harlow, S. D., Avis, N. E., Waetjen, L. E., Kravitz, H. M., Cauley, J. A., & Greendale, G. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45863-7.00035-4
Crosstalk between estrogen signaling and Fas-mediated apoptosis determines neuronal resilience after menopause
Rodak, P., Mróz, K., Pacwa, A., Gąsiorek, A., Machna, B., Olakowska, E., Lewin‐Kowalik, J., Amadio, M., & Smędowski, A. (2026) · Experimental Eye Research · doi:10.1016/j.exer.2026.111190
Imeglimin halts cyclophosphamide-induced ovarian injury: a dual modulation of TLR4/NF-κB/NLRP3-driven inflammation and AMPK/SIRT1/PGC-1α pathways
Mohyeldin, R. H., Sharata, E. E., Abdelnaser, M., Attya, M. E., Kotb, A. S. M., Rofaeil, R. R., Elghfar, M. H. M. A., & Khalifa, Y. M. M. A. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05885-7 · Cited by 1
Systemic control and inter-organ communication of ovarian agingPreprint
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Familial Gynecologic Cancers: Whom to Screen and How to Manage?
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Authors: Rocca, W. A., Grossardt, B. R., Miller, V. M., Shuster, L. T., & Brown, R. D.
Affiliations: Mayo Clinic (US)
Department of Medical Sciences (BY)
Corresponding author: Rocca, Walter A.
ORCID: Rocca, Walter A.
Grossardt, Brandon R.
Miller, Virginia M.
Brown, Robert D.
Venue: Menopause
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2012-03
Volume: 19
Issue: 3
Pages: 272-277
ISSN: 1072-3714 (ISSN-L)
DOI: 10.1097/gme.0b013e31822a9937
PMC: PMC3258468
OpenAlex: W2016373832
Semantic Scholar: 5046b0fb75f713a0ec75734faf7bbf9842dc66db
Cited by: 188
References: 53
Citations by year: 2026: 8 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 5 · 2021: 10 · 2020: 11 · 2019: 31 · 2018: 11 · 2017: 14 · 2016: 15 · 2015: 11 · 2014: 17 · 2013: 13 · 2012: 12
FWCI: 1.92
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Menopause The Journal of The North American Menopause Society (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (R01AG034676, AG-034676)
National Institute of Neurological Disorders and Stroke (NS 033978, R01NS033978)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Keywords: premature menopause, early menopause, ischemic stroke, estrogen, estrogen deprivation, bilateral oophorectomy, hormone therapy, timing hypothesis, ovarian function
MeSH terms: Female, Humans, Menopause, Premature, Ovariectomy, Risk, Cohort Studies, Hormone Replacement Therapy, Stroke

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Premature menopause or early menopause and risk of ischemic stroke

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