Age At Menopause: A Female Risk Factor of Stroke?

HomeStrokeVol. 52, No. 8Age At Menopause: A Female Risk Factor of Stroke? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBAge At Menopause: A Female Risk Factor of Stroke? Hanne Christensen, MD, DMSci Charlotte CordonnierMD, PhD Hanne ChristensenHanne Christensen Correspondence to: Hanne Christensen, MD, DMSci, Department of Neurology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Copenhagen NV 2400, Denmark. Email E-mail Address: [email protected] https://orcid.org/0000-0002-7472-3194 Department of Neurology, Bispebjerg Hospital and University. Copenhagen, Denmark (H.C.). and Charlotte CordonnierCharlotte Cordonnier https://orcid.org/0000-0002-5697-6892 Université de Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, F-59000, France (C.C.). Originally published3 Jun 2021https://doi.org/10.1161/STROKEAHA.121.034828Stroke. 2021;52:2592–2593This article is a commentary on the followingAge at Menopause and Risk of Ischemic and Hemorrhagic StrokeSee related article, p 2583Stroke is not only a leading cause of disability but is also a leading cause of death worldwide—particularly in women. The anticipated increase in the average age of the female population worldwide will lead to an increase in the prevalence of stroke in women and will challenge our healthcare systems. Women differ from men in a multitude of ways, including anatomy, vascular biology, coagulation, lifestyle, and societal roles. Among those differences, hormonal profiles probably constitute more prominent differences. Women are not men like others. Although risk of stroke differs throughout the life course, 3 stages of women's lives have specificities in terms of stroke risk: child-bearing age, postmenopause, and over 80 years of age.1 In the era of personalized and precision medicine, our knowledge of women's specificities is still incomplete.In this issue of Stroke, Welten et al2 followed up 16 244 postmenopausal Dutch women during a mean of 15 years. They showed that the age of menopause matters in the risk of future ischemic stroke: there is a 2% risk reduction of stroke for each year the menopause occurs later. The impact of a later menopause was observed in ischemic stroke but failed to reach statistical significance in hemorrhagic stroke, likely due to low numbers of hemorrhagic events. The authors evaluated both natural and surgical menopause. Interestingly, the association appeared stronger in natural than in surgical menopause.On this topic, data are controversial, and Welten et al2 raise important methodological issues that could explain the heterogeneity of data. For example, the methodological notion of immortal time bias is an important one.After menopause, the burden of vascular risk factors increase,3 and 1 in 5 women versus 1 in 6 men at the age of 55 years will suffer a stroke event during their remaining lifetime.4Overall, the epidemiological association of age at menopause is confirmed by Welten et al,2 but the basis of this association remains unclear. Several potential explanations are present and especially the role of estrogen has been explored: estrogen has vasoactive properties assumed to support vascular health, but hormone replacement therapy was shown to increase risk of stroke in several trials,5 although it has been hypothesized that this effect related to initiation of hormone replacement therapy years after menopause. It is also possible that menopause is at least partly an epiphenomenon to other risk factors which covariates with both risk of stroke and age of menopause including socioeconomic status6,7 or smoking.Many questions remain unanswered. First, is early menopause associated with specific vascular risk profiles, such as hypertension, hyperlipidemia, or does it trigger some risk factors such as atrial fibrillation? Furthermore, is there a pattern in stroke types (large vessel disease/small vessel disease/cardioembolic stroke) in women with stroke and early menopause? A translational approach will be of interest here. Although epidemiological data will bring large, observational data, refined animal models could also contribute to understanding a hypothetical causal relation.Exploring this topic would be of potential clinical value as age at menopause could be an element contributing to a personalized risk assessment for primary stroke. While existing data does not support therapeutic decisions on drug therapy influenced by age at menopause, nonpharmacological interventions (targeting smoking, alcohol consumption, diet, or physical activity) could be promoted in consultations related to menopause.Sources of FundingNone.Disclosures Dr Christensen reports Consulting Editor (Stroke). Dr Cordonnier reports personal fees from Boehringer-Ingelheim, personal fees from Bristol Myers Squibb (BMS), personal fees from Biogen, personal fees from AstraZeneca, and grants from French ministry of health outside the submitted work; and Associate editor (Stroke).FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 2593.Correspondence to: Hanne Christensen, MD, DMSci, Department of Neurology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg Bakke 23, Copenhagen NV 2400, Denmark. Email hanne.krarup.[email protected]dkReferences1. Cordonnier C, Sprigg N, Sandset EC, Pavlovic A, Sunnerhagen KS, Caso V, Christensen H; Women Initiative for Stroke in Europe (WISE) Group. Stroke in women — from evidence to inequalities.Nature Reviews Neurol. 2017; 13:221–532. doi: 10.1038/nrneurol.2017.95Google Scholar2. Welten SJGC, Onland-Moret NC, Boer JMA, Verschuren WMM, van der Schouw YT. Age at menopause and risk of ischemic and hemorrhagic stroke.Stroke. 2021; 52:2583–2591.doi: 10.1161/STROKEAHA.120.030558LinkGoogle Scholar3. George J, Rapsomaniki E, Pujades-Rodriguez M, Shah AD, Denaxas S, Herrett E, Smeeth L, Timmis A, Hemingway H. How does cardiovascular disease first present in women and men? incidence of 12 cardiovascular diseases in a contemporary cohort of 1,937,360 people.Circulation. 2015; 132:1320–1328. doi: 10.1161/CIRCULATIONAHA.114.013797LinkGoogle Scholar4. Petrea RE, Beiser AS, Seshadri S, Kelly-Hayes M, Kase CS, Wolf PA. Gender differences in stroke incidence and poststroke disability in the Framingham heart study.Stroke. 2009; 40:1032–1037. doi: 10.1161/STROKEAHA.108.542894LinkGoogle Scholar5. Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women.Cochrane Database Syst Rev. 2017; 1:CD004143. doi: 10.1002/14651858.CD004143.pub5MedlineGoogle Scholar6. Lawlor DA, Ebrahim S, Smith GD. The association of socio-economic position across the life course and age at menopause: the British Women's Heart and Health Study.BJOG. 2003; 110:1078–1087.Google Scholar7. Marshall IJ, Wang Y, Crichton S, McKevitt C, Rudd AG, Wolfe CD. The effects of socioeconomic status on stroke risk and outcomes.Lancet Neurol. 2015; 14:1206–1218. doi: 10.1016/S1474-4422(15)00200-8CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesAge at Menopause and Risk of Ischemic and Hemorrhagic StrokeSabrina J.G.C. Welten, et al. Stroke. 2021;52:2583-2591 August 2021Vol 52, Issue 8Article InformationMetrics Download: 735 © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.034828PMID: 34078105 Originally publishedJune 3, 2021 Keywordswomenischemic strokemenopauserisk factorEditorialsPDF download SubjectsCerebrovascular Disease/Stroke