Premature menopause or early menopause and risk of ischemic stroke
Open accessAbstract
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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Treatment with estrogens until age 45 years or longer may reduce the risk of cardiovascular disease and mortality.
“Treatment with estrogens until age 45 years or longer may reduce the risk of cardiovascular disease and mortality (47,49,51).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [49]
The Results (Findings from individual studies; page unavailable) report that women who had bilateral oophorectomy before age 45 and received hormone therapy through age 45 did not have increased cardiovascular-disease risk, and suggest that premature estrogen deficiency may explain increased cardiovascular mortality. This supports a possible benefit, but the evidence concerns women with early bilateral oophorectomy and cardiovascular mortality—not a general reduction in mortality for everyone treated with estrogen until age 45 or longer. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTreatment with estrogens through age 45 years or longer may reduce the risk of cardiovascular disease and mortality.
“Treatment with estrogens through age 45 years or longer may reduce the risk of cardiovascular disease and mortality (47,49,51).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [49]
The Results (Findings from individual studies; page unavailable) report that women who underwent bilateral oophorectomy before age 45 and received hormone therapy through age 45 did not have an increased risk of cardiovascular disease, including stroke. The paper also suggests that premature estrogen deficiency may explain increased cardiovascular mortality. The claim omits that population restriction and does not specify cardiovascular mortality; the paper does not establish a reduction in mortality generally. (LLM, conf=0.83)
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Management of menopause: a view towards prevention
Lobo, R. A., & Gompel, A. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00269-2 · Cited by 180 · see citing works
Sex-Specific Physiology and Cardiovascular Disease
SHUFELT, C. L., Pacheco, C., Tweet, M. S., & Miller, V. M. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77932-4_27 · Cited by 172 · see citing works
Self-citationPrediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer
Chow, E. J., Chen, Y., Hudson, M. M., Feijen, E. A. M., Kremer, L. C. M., Border, W. L., Green, D. M., Meacham, L. R., Mulrooney, D. A., Ness, K. K., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.8673 · Cited by 154 · see citing works
“9) Median current age, years (range) 32 (6-59) 28 (18-63) 31 (5-56) Median time since diagnosis, years (range) 24 (5-39) 19 (10-48) 23 (5-45) Cancer diagnosis Acute lymphoblastic leukemia 3,987 (30.”
Effect of primary ovarian insufficiency and early natural menopause on mortality: a meta-analysis
Tao, X.-Y., Zuo, A.-Z., Wang, J.-Q., & Tao, F.-B. (2016) · Climacteric · doi:10.3109/13697137.2015.1094784 · Cited by 147 · see citing works
Current Concepts in Premature Ovarian Insufficiency
Maclaran, K., & Panay, N. (2015) · Women s Health · doi:10.2217/whe.14.82 · Cited by 134 · see citing works
Clinical Effects of Early or Surgical Menopause
Kingsberg, S. A., Larkin, L. C., & LIU, J. H. (2020) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000003729 · Cited by 153 · see citing works
Sex differences in stroke: The contribution of coagulation
Roy-O’Reilly, M. A., & McCullough, L. D. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.02.011 · Cited by 129 · see citing works
“(2014), http:// menopause (Roger et al., 2012; Rocca et al., 2012).”
Premature Ovarian Insufficiency and Long-Term Health Consequences
Tsiligiannis, S., Panay, N., & Stevenson, J. C. (2019) · Current Vascular Pharmacology · doi:10.2174/1570161117666190122101611 · Cited by 113 · see citing works
Prescribing menopausal hormone therapy: an evidence-based approach
Sood, R., Faubion, S. S., Kuhle, C. L., Thielen, J. M., & Shuster, L. T. (2014) · International Journal of Women s Health · doi:10.2147/ijwh.s38342 · Cited by 105 · see citing works
“For women with early estrogen deficiency due to premature onset of menopause, there is accumulating data on protection against stroke with the administration of estrogen following oophorectomy.(33) Early estrogen deprivation appears to increase a woman’s risk of stroke, and estrogen therapy may reduce this risk.”
Self-citationThe Importance of Considering Sex Differences in Translational Stroke Research
Ahnstedt, H. W., McCullough, L. D., & Cipolla, M. J. (2016) · Translational Stroke Research · doi:10.1007/s12975-016-0450-1 · Cited by 107 · see citing works
“The differential effect of estrogen in experimental and clinical studies might originate from the timing of hormone therapy, the age of the women, and the number of years since menopause [92].”
Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses
Holmegard, H. N., Nordestgaard, B. G., Jensen, G. B., Tybjærg‐Hansen, A., & Benn, M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2687 · Cited by 102 · see citing works
“Physically inactive 194 (38) 1288 (35) 140 (36) 26 (24) 193 (24) 29 (29) 145 (35) 981 (34) 106 (33)”
BackgroundLifestyle and dietary factors determine age at natural menopause
Sapre, S. A., & Thakur, R. (2014) · Journal of Mid-life Health · doi:10.4103/0976-7800.127779 · Cited by 100 · see citing works
Henderson, V. W., & Lobo, R. A. (2012) · Climacteric · doi:10.3109/13697137.2012.656254 · Cited by 94 · see citing works
Chiang, C., Lewis, L. R., Borkowski, G., & Flaws, J. A. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.114952 · Cited by 93 · see citing works
Reproductive and Developmental Toxicology
Carlson, L. M., Chiang, C., Hotchkiss, A. K., Lizarraga, L. E., Luben, T., Makris, S. L., Radke, E. G., Weitekamp, C. A., & Yost, E. E. (2023) · Wiley eBooks · doi:10.1002/0471125474.tox123 · Cited by 92 · see citing works
Premature ovarian insufficiency: Pathogenesis and management
Fenton, A. J. (2015) · Journal of Mid-life Health · doi:10.4103/0976-7800.172292 · Cited by 91 · see citing works
“However, this is not a universal finding in all studies.[18-26] Hormone therapy appears to reduce the risk of cardiovascular disease in young women with POI.”
BackgroundFinch, A., Evans, D. G., & Narod, S. A. (2012) · Women s Health · doi:10.2217/whe.12.41 · Cited by 90 · see citing works
“reviewed observational studies of menopause, estrogen use and ischemic stroke [16].”
BackgroundHRT optimization, using transdermal estradiol plus micronized progesterone, a safer HRT
L’Hermite, M. (2013) · Climacteric · doi:10.3109/13697137.2013.808563 · Cited by 79 · see citing works
Zhu, D., Chung, H., Pandeya, N., Dobson, A. J., Hardy, R., Kuh, D. J., Brunner, E. J., Bruinsma, F., Giles, G. G., Demakakos, P., et al. (2019) · European Journal of Epidemiology · doi:10.1007/s10654-019-00490-w · Cited by 77 · see citing works
Remote Ischemic Perconditioning is Effective After Embolic Stroke in Ovariectomized Female Mice
Hoda, M. N., Bhatia, K., Hafez, S. S., Johnson, M. H., Siddiqui, S., Ergul, A., Zaidi, S. K., Fagan, S. C., & Hess, D. C. (2014) · Translational Stroke Research · doi:10.1007/s12975-013-0318-6 · Cited by 74 · see citing works
“Since gain in the body weight after ovariectomy is a very common ovariectomy-associated problem in women [26–28], we assume that 2-months post-OVX mice better models ‘surgical menopause’ than earlier time points.”
BackgroundMenopausal Hormone Therapy and Cardiovascular Risk: Where are we Now?
Anagnostis, P. G., Paschou, S. Α., Katsiki, N., Krikidis, D., Lambrinoudaki, I. V., & Goulis, D. G. (2018) · Current Vascular Pharmacology · doi:10.2174/1570161116666180709095348 · Cited by 75 · see citing works
Relationship between age at natural menopause and risk of heart failure
Rahman, I., Åkesson, A., & Wolk, A. (2014) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000261 · Cited by 74 · see citing works
Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease
Scott, E. L., & Brann, D. W. (2012) · Brain Research · doi:10.1016/j.brainres.2012.12.015 · Cited by 73 · see citing works
“…of age) have increased risks for ischemic stroke, dementia, and mortality from neurological disorders, which can be ameliorated with timely replacement of E2 until the age of natural menopause (Rivera et al., 2009; Rocca et al., 2007; Rocca et al., 2011; Rocca et al., 2012; Shuster et al., 2010).”
BackgroundElevated ischemic stroke risk among women living with HIV infection
Chow, F. C., Regan, S., Zanni, M. V., Looby, S. E. D., Bushnell, C., Meigs, J. B., Grinspoon, S. K., Feske, S. K., & Triant, V. A. (2017) · AIDS · doi:10.1097/qad.0000000000001650 · Cited by 73 · see citing works
Estrogen receptors and ischemic neuroprotection: Who, what, where, and when?
Schreihofer, D. A., & Ma, Y. (2013) · Brain Research · doi:10.1016/j.brainres.2013.02.051 · Cited by 68 · see citing works
Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors
Phillips, N. S., Stratton, K. L., Williams, A. M., Ahles, T. A., Ness, K. K., Cohen, H. J., Edelstein, K., Yasui, Y., Oeffinger, K. C., Chow, E. J., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.16077 · Cited by 68 · see citing works
Prókai, L., Nguyen, V., Szarka, S., Garg, P., Sabnis, G. J., Bimonte‐Nelson, H. A., McLaughlin, K. J., Talboom, J. S., Conrad, C. D., Shughrue, P. J., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aab1290 · Cited by 68 · see citing works
“Symptoms of premature menopause and also of menopause resulting from reproductive senescence include, among others, hot flushes, depression, cognitive impairment, and an increased risk of ischemic stroke (5, 6, 34).”
BackgroundYang, L., Lin, L., Kartsonaki, C., Yu, C., Chen, Y., Bian, Z., Xie, K., Jin, D., Li, L., Lv, J., et al. (2017) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.117.004235 · Cited by 63 · see citing works
“In terms of subtypes of stroke, the association tended to be restricted to ischemic stroke.(29) A”
BackgroundPredictors of early menopause in HIV-infected women: a prospective cohort study
Calvet, G. A., Grinsztejn, B. G. J., Quintana, M. D. S. B., Derrico, M., Jalil, E. M., Cytryn, A., de Andrade, A. C. V., Moreira, R. I., Alves, M. R., Veloso, V. G., et al. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2014.12.040 · Cited by 66 · see citing works
PPARγ activation rescues mitochondrial function from inhibition of complex I and loss of PINK1
Corona, J. C., de Souza, S. C., & Duchen, M. R. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2013.12.012 · Cited by 62 · see citing works
Sex hormone replacement therapy in Turner syndrome—impact on morbidity and mortality
Viuff, M. H., Berglund, A., Juul, S., Andersen, N. H., Stochholm, K., & Gravholt, C. H. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz039 · Cited by 62 · see citing works
Challenging and Complex Decisions in the Management of the BRCA Mutation Carrier
Stan, D. L., Shuster, L. T., Wick, M. J., Swanson, C. L., Pruthi, S., & Bakkum-Gamez, J. N. (2013) · Journal of Women s Health · doi:10.1089/jwh.2013.4407 · Cited by 58 · see citing works
“Extensive evidence, including that from large, wellcharacterized cohorts of women including the Nurses’ Health Study (NHS) and the Olmsted County Study of Oophorectomy and Aging (OCSOA), as well as the National Health and Nutrition Examination Survey, links early menopause and BO to an increased risk of mortality,(95,…”
Self-citationSex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause
Miller, V. M., Garovic, V. D., Kantarci, K., Barnes, J. N., Jayachandran, M., Mielke, M. M., Joyner, M. J., Shuster, L. T., & Rocca, W. A. (2013) · Biology of Sex Differences · doi:10.1186/2042-6410-4-6 · Cited by 56 · see citing works
“The risk of developing hypertension, ischemic heart disease, myocardial infarction and stroke increases in women after the onset of menopause, whether natural or surgically induced [2,73].”
BackgroundSelf-citationSex hormones and stroke: Beyond estrogens
Sohrabji, F., Okoreeh, A. K., & Panta, A. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.10.010 · Cited by 59 · see citing works
Laronda, M. M., Burdette, J. E., Kim, J. J., & Woodruff, T. K. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt374 · Cited by 53 · see citing works
“Additionally, studies in postmenopausal women and women who have undergone premature ovarian failure demonstrate that hormone replacement regimens could improve the patients overall health, quality of life and is recommended by the American Association of Clinical Endocrinologists [37-40].”
BackgroundEffects of the Menstrual Cycle on Neurological Disorders
Roeder, H. J., & Leira, E. C. C. (2021) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-021-01115-0 · Cited by 53 · see citing works
Hanson, H., Kulkarni, A. A., Loong, L., Kavanaugh, G., Torr, B., Allen, S., Ahmed, M., Antoniou, A. C., Cleaver, R., Dabir, T. A., et al. (2022) · Journal of Medical Genetics · doi:10.1136/jmg-2022-108898 · Cited by 53 · see citing works
BRCA mutation genetic testing implications in the United States
Bayraktar, S., & Arun, B. (2016) · The Breast · doi:10.1016/j.breast.2016.11.021 · Cited by 51 · see citing works
Bacon, E. R., & Brinton, R. D. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.040 · Cited by 51 · see citing works
Acosta-Martínez, M. (2020) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.264598 · Cited by 51 · see citing works
“For instance, menopause increases the risk of stroke in women, and early menopause is associated with a two-fold increase in risk for ischemic stroke (Rocca et al., 2012).”
BackgroundChiang, C., Lewis, L. R., Borkowski, G., & Flaws, J. A. (2020) · Reproductive Toxicology · doi:10.1016/j.reprotox.2019.12.006 · Cited by 48 · see citing works
Sex Differences in Ischemia/Reperfusion Injury: The Role of Mitochondrial Permeability Transition
Fels, J. A., & Manfredi, G. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02769-6 · Cited by 45 · see citing works
Cui, J., & Wang, Y. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-023-01330-y · Cited by 45 · see citing works
“Cardiovascular disease and stroke stand out as the leading causes of reduced life expectancy among untreated POI patients compared to age-matched controls (Archer 2009; [86, 87].”
BackgroundKemper, M. F., Zhao, Y., Duckles, S. P., & Krause, D. N. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.159 · Cited by 38 · see citing works
Spanish consensus on premature menopause
Mendoza, N., Juliá, M. D., Galliano, D., Coronado, P., Díaz, B. N., Fontes, J., Gallo, J. L. R., García, A. G., Gasull, M. G., Munnamy, M., et al. (2014) · Maturitas · doi:10.1016/j.maturitas.2014.11.007 · Cited by 38 · see citing works
Pilar Vigil, P., Ana, C. L. D., Flores, B., Rioseco, H., & Serrano, F. G. (2017) · The Linacre Quarterly · doi:10.1080/00243639.2017.1394053 · Cited by 38 · see citing works
“gen and/or androgen replacement in these women will improve mood, and mitigate the risk of cardiovascular disease (Rocca et al. 2012), osteoporosis (Svejme et al.”
BackgroundSex and stroke risk factors: A review of differences and impact
Hanna, M., Wabnitz, A., & Grewal, P. (2024) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2024.107624 · Cited by 41 · see citing works
Premature menopause and risk of neurological disease: Basic mechanisms and clinical implications
Scott, E. L., Zhang, Q.-G., Vadlamudi, R. K., & Brann, D. W. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.01.013 · Cited by 36 · 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).”
BackgroundThe role of lifestyle medicine in menopausal health: a review of non-pharmacologic interventions
Anekwe, C. V., Cano, A., Mulligan, J., Ang, S. B., Johnson, C. N., Panay, N., Schaedel, Z., Akam, E. Y., Porterfield, F., Wang, E., et al. (2025) · Climacteric · doi:10.1080/13697137.2025.2548806 · Cited by 38 · see citing works
“In a large review of observational studies, women who underwent natural or surgical menopause before the age of 40 years had a significantly increased risk of cardiovascular diseases [232].”
Schaufelberger, S., Rosselli, M., Barchiesi, F., Gillespie, D. G., Jackson, E. K., & Dubey, R. K. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00418.2015 · Cited by 34 · see citing works
Menopausal Age and Chronic Diseases in Elderly Women: A Cross-Sectional Study in Northeast China
Fu, Y., Yu, Y., Wang, S., Kanu, J. S., You, Y., Liu, Y., Zhang, Y., Liu, Y., Li, B., Tao, Y., et al. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13100936 · Cited by 34 · see citing works
“Early menopause has been reported to be associated with all-cause mortality [2,3] and has numerous adverse effects on cardiovascular disease [4], neurological diseases, and osteoporosis [5].”
BackgroundAnalysis of second-harmonic-generation microscopy in a mouse model of ovarian carcinoma
Watson, J. M., Rice, P. F. S., Utzinger, U., Barton, J. K., Marion, S. L., Hoyer, P. B., BREWER, M. A., Davis, J. R., & Rodrı́guez, J. J. (2012) · Journal of Biomedical Optics · doi:10.1117/1.jbo.17.7.076002 · Cited by 33 · see citing works
Yang, H. J., Suh, P. S., Kim, S. J., & Lee, S. Y. (2015) · Journal of Preventive Medicine and Public Health · doi:10.3961/jpmph.15.021 · Cited by 30 · see citing works
“Menopause is also associated with dyslipidemia [3], hypertension [4], and ischemic stroke [5].”
BackgroundTime Trends in Unilateral and Bilateral Oophorectomy in a Geographically Defined American Population
Erickson, Z., Rocca, W. A., Smith, C. Y., Rocca, L. G., Stewart, E. A., Laughlin-Tommaso, S. K., & Mielke, M. M. (2022) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000004728 · Cited by 26 · see citing works
Self-citationAortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women
Barnes, J. N., Harvey, R. E., Zuk, S. M., Lundt, E. S., Lesnick, T. G., Gunter, J. L., Senjem, M. L., Shuster, L. T., Miller, V. M., Jack, C. R., et al. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8476-1 · Cited by 27 · see citing works
“During the transition to and after menopause, the risk of developing hypertension, ischemic heart disease, and stroke increases in women [21].”
BackgroundSelf-citationRofaeil, R. R., Sharata, E. E., Attya, M. E., Abo‐Youssef, A. M., Hemeida, R. A. M., & Khalaf, M. M. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115406 · Cited by 24 · see citing works
Sehl, M. E., & Ganz, P. A. (2018) · JNCI Cancer Spectrum · doi:10.1093/jncics/pky035 · Cited by 24 · see citing works
“In addition, the Mayo Clinic Study of Oophorectomy and Aging revealed higher rates of stroke (126) and multimorbidity in women undergoing oophorectomy for a noncancer indication (4), with an increased risk of depression,”
BackgroundAge at natural menopause impacts cerebrovascular reactivity and brain structure
Moir, M. E., Corkery, A. T., Senese, K. A., Miller, K. B., Pearson, A. G., Loggie, N. A., Howery, A. J., Gaynor‐Metzinger, S. H. A., Cody, K. A., Eisenmenger, L. B., et al. (2023) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00228.2022 · Cited by 22 · see citing works
Menstrual Factors and Stroke Incidence in Japanese Postmenopausal Women: The Ohasama Study
Murakami, K., Metoki, H., Satoh, M., Asayama, K., Hosaka, M., Matsuda, A., Inoue, R., Tsubota‐Utsugi, M., Murakami, T., Nomura, K., et al. (2016) · Neuroepidemiology · doi:10.1159/000452220 · Cited by 22 · see citing works
Podfigurna, A., & Męczekalski, B. (2018) · Menopause Review/Przegląd Menopauzalny · doi:10.5114/pm.2018.78551 · Cited by 22 · see citing works
“However, at this time, evidence is insufficient to recommend hormone replacement therapy for the sole purpose of preventing cardiovascular disease or stroke [16].”
BackgroundMenopausal syndrome limited to hot flushes and sweating a representative survey study
Weidner, K., Croy, I., Siepmann, T., Brähler, E., Beutel, M. E., & Bittner, A. (2017) · Journal of Psychosomatic Obstetrics & Gynecology · doi:10.1080/0167482x.2017.1291624 · Cited by 21 · see citing works
Cordova, R., Kiekens, K. C., Burrell, S. L., Drake, W. K., Kmeid, Z., Rice, P. F. S., Rocha, A. D., Diaz, S., Yamada, S., Yozwiak, M. L., et al. (2021) · Journal of Biomedical Optics · doi:10.1117/1.jbo.26.7.076001 · Cited by 20 · see citing works
Pulsed administration for physiological estrogen replacement in mice
Corciulo, C., Scheffler, J. M., Gustafsson, K. L., Drevinge, C., Humeniuk, P., Pons, A., POUTANEN, M. H., Ohlsson, C., Lagerquist, M. K., & Islander, U. (2021) · F1000Research · doi:10.12688/f1000research.54501.1 · Cited by 20 · see citing works
Craniopharyngioma—An update on metabolic and cognitive complications and new therapy
Erfurth, E. M. (2023) · Journal of Internal Medicine · doi:10.1111/joim.13684 · Cited by 21 · see citing works
The Relationship of Fertility, Lifestyle, and Longevity Among Women
Lockhart, P., Martin, P., Johnson, M. A., Shirtcliff, E. A., & Poon, L. W. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw158 · Cited by 20 · see citing works
“In a study out of Japan, there was a 21% increased risk of stroke in women who had begun menopause under the age of 44 years, regardless of whether it was natural or induced (30).”
BackgroundLi, Y., Zhao, D. H., Wang, M., Sun, J., Liu, J., Qi, Y., Hao, Y., Deng, Q., Liu, J., Liu, J., et al. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-01919-5 · Cited by 20 · see citing works
“A previous review of observational studies reported that premature or early menopause was associated with an increased risk of ischemic stroke and that hormonal therapy before age 50 years may partly offset the increased risk; the authors suggested that estrogen may be a protective factor for ischemic stroke before ag…”
BackgroundTerra, L., Hooning, M. J., Heemskerk‐Gerritsen, B. A. M., van Beurden, M., van Lennep, J. E. R., van Doorn, H. C., de Hullu, J. A., Mom, C. H., van Dorst, E. B. L., Mourits, M. J. E., et al. (2020) · JMIR Research Protocols · doi:10.2196/24414 · Cited by 20 · see citing works
Genetic Polymorphisms in the ESR1 Gene and Cerebral Infarction Risk: A Meta-Analysis
Gao, H., Gao, L., & Wen, J. (2014) · DNA and Cell Biology · doi:10.1089/dna.2013.2270 · Cited by 18 · see citing works
“Indeed, estrogen is protective for cerebral infarction in women younger than 50 years, where women did not experience premature or early menopause or considering no prophylactic bilateral oophorectomy before the onset of natural menopause (Lisabeth et al. , 2009; Rocca et al. , 2012).”
Kim, J., Choe, J.-P., Park, J.-H., Yoo, E., & Lee, J. M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18147256 · Cited by 18 · see citing works
“In particular, early menopause has been announced to be related to all-cause mortality [11,12] and has a lot of negative effects on cardiovascular disease [13], neurological diseases, and osteoporosis [14].”
BackgroundPrimary Prevention of Cardiovascular Disease with HRT
Maclaran, K., & Stevenson, J. C. (2011) · Women s Health · doi:10.2217/whe.11.87 · Cited by 18 · see citing works
“Furthermore, menopause is associated with a number of adverse changes to classical cardiovascular risk factors, and women experiencing premature loss of ovarian function have an increased risk of ischemic heart disease [3,4] and possibly stroke [5].”
BackgroundFrom head to toe: Sex and gender differences in the treatment of ischemic cerebral disease
Falsetti, L., Viticchi, G., Buratti, L., Balucani, C., Marra, A. M., & Silvestrini, M. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.05.006 · Cited by 17 · see citing works
“An early menopause has also been associated to an increased rate of cardiovascular events and vascular death[9,10] and the risk increases further in the presence of hormone therapy [11].”
BackgroundDamiati, S. (2018) · Journal of Medical Biochemistry · doi:10.2478/jomb-2018-0025 · Cited by 16 · see citing works
“By assuming that 50 years of age is approximately the age of onset of menopause in women (30, 31), it has been shown that ADMA levels increased with the onset of menopause, which may be attributed to changes in sex hormones concentrations as an important factor in the menstrual cycle (32).”
BackgroundRuberti, O. M., & Rodrigues, B. L. (2019) · Current Cardiology Reviews · doi:10.2174/1573403x15666190729153026 · Cited by 16 · see citing works
“For example, the Mayo Clinic Cohort Study of Aging Oophorectomy revealed that early surgical induction of menopause increased the risk of ischemic stroke, Parkinson's disease, doubled the risk of dementia, increased risk of depression and anxiety as well as the risk of mortality due to neurological disorders increased…”
BackgroundRYMER, J. M., Brian, K., & Regan, L. (2019) · BMJ · doi:10.1136/bmj.l5928 · Cited by 15 · see citing works
Miller, V. M., & Manson, J. E. (2013) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-013-0305-1 · Cited by 14 · see citing works
“Indeed, the “window of opportunity” for stroke prevention may not be comparable to that for cardiac events [19].”
Self-citationMossa, F., Latham, K. E., Ireland, J. J., & Veiga‐Lopez, A. (2019) · Molecular Reproduction and Development · doi:10.1002/mrd.23239 · Cited by 13 · see citing works
“Consistent with these associations, CVD is linked to a diminished ovarian reserve (Verit et al., 2014), the single greatest contributor to infertility in women (SART, 2013), and to menopause (Kannel, Hjortland, McNamara, & Gordon, 1976; Rocca et al., 2012).”
BackgroundReproductive hormones in relation to white matter hyperintensity volumes among midlife women
Thurston, R. C., Chang, Y.-F., Wu, M., Harrison, E. M., Aizenstein, H. J., Derby, C. A., Barinas‐Mitchell, E., & Maki, P. M. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14093 · Cited by 12 · see citing works
“7,8 Research links an earlier natural menopause or younger/premenopausal oophorectomy with elevated stroke risk 9–11 and a longer reproductive lifespan with lowerstrokerisk.”
BackgroundCardiovascular Disease After Hysterectomy in the Nurses' Health Study and Nurses' Health Study II
Thao, V., Borah, B. J., Stewart, E. A., Farland, L. V., Laughlin-Tommaso, S. K., Khan, Z., Coutinho, T., & Rassier, S. L. C. (2025) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000005902 · Cited by 12 · see citing works
Hsieh, Y., Jeng, J., Lin, H., Hu, C., Yu, C.-C., Lien, L., Peng, G., Chen, C.-I., Tang, S., Chi, N., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047773 · Cited by 12 · see citing works
“Previous population-based epidemiological studies reported stroke incidence rate to be lower in women during midlife than that in either older aged women or men [1,2].”
BackgroundResultSexuality and Intimacy Among Older Women Living with HIV: a Systematic Review
Stanton, A. M., Goodman, G. R., Looby, S. E. D., Robbins, G. K., & Psaros, C. (2019) · Current Sexual Health Reports · doi:10.1007/s11930-019-00227-6 · Cited by 12 · see citing works
The association between chronic diseases and the age at natural menopause: a systematic review
Tehrani, F. R., & Amiri, M. (2021) · Women & Health · doi:10.1080/03630242.2021.1992067 · Cited by 12 · see citing works
“Earlier studies have documented that early age at natural menopause (ANM) can be related to numerous health outcomes, such as increased risks of cardiovascular disease, neurological disorders, psycho-emotional disturbances, and osteoporosis (Cancer 2012; Fu et al. 2016; Georgakis et al. 2016; McPherson et al. 1996; Ra…”
BackgroundFactors associated with early menopause among women in Nigeria
Agaba, P. A., Meloni, S., Sule, H. M., Ocheke, A. N., Agaba, E. I., Idoko, J. A., & Kanki, P. J. (2017) · Journal of Virus Eradication · doi:10.1016/s2055-6640(20)30333-2 · Cited by 14 · see citing works
Mittal, M., Savvas, M., Narvekar, N. N., Panay, N., & Hamoda, H. (2014) · Post Reproductive Health · doi:10.1177/2053369114540883 · Cited by 11 · see citing works
“A review of seven observational studies showed an increased risk of all stroke including ischaemic stroke in women who underwent an early menopause before the age of 50 years, with the risk reduced in women who received hormone therapy.(19) All routes of estrogen administration can effectively treat menopausal symptom…”
BackgroundBarboza, L. N., Prando, T. B. L., Dalsenter, P. R., Gasparotto, F. M., Gasparotto, F., Jacomassi, E., Araújo, V. D. O., Lourenço, E. L. B., & Gasparotto, A. (2014) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2014/958291 · Cited by 10 · see citing works
“Usually it occurs between 45 and 54 years of age and can present a number of comorbidities (mainly bone loss and cardiovascular disease) influenced by lifestyle, age, and genetic characteristics [1].”
BackgroundWyse, Â. T. D. S., Siebert, C., Bobermin, L. D., dos Santos, T. M., & Quincozes‐Santos, A. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00128-5 · Cited by 9 · see citing works
- 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.
- Venue
- Menopause
- Published
- 2012-03
- Volume
- 19
- Issue
- 3
- Pages
- 272-277
- ISSN
- 1072-3714 (ISSN-L)
- 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 › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Epidemiology › 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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