World Stroke Organization The Paper of The Month – March
02 Mar 2023Title: The uniqueness of stroke risk factors in women
Title: The uniqueness of stroke risk factors in women
Author: Prof. Dr. Anita Arsovska – WSA Associate Commissioning Editor
This article is a commentary on the following: Bushnell CD, Kapral MK. Stroke in Women and Unique Risk Factors. 2023
Summary of the findings
This article provides a summary of the latest studies regarding stroke risk factors in women (1). The Nurses’ Health Study II provides new data on the association between laparoscopically proven endometriosis and future stroke, accounting for the mediation effects of hysterectomy and oophorectomy. In a cohort of women from China, the relationship between hysterectomy, oophorectomy, and stroke is further clarified, accounting for the age at which the procedure is performed. The UK Biobank study provides new information on the relationship between oral contraceptive and hormone replacement therapy and stroke, with analytical techniques that focus on the timing of events related to duration of exposure. Two new meta-analyses address the question of whether sex differences exist in the presentation of stroke symptoms.The findings suggest that while clinicians should be aware that women may be more likely than men to present with altered level of consciousness or headache and investigate accordingly, current stroke awareness campaigns focusing on traditional symptoms are likely appropriate for both women and men.
Commentary
Stroke is the third leading cause of death in women in the United States and is a leading cause of disability. In USA, each year 55 000 more women than men have a stroke, mostly because women live longer than men. The majority of stroke incidence can be attributed to traditional vascular risk factors that occur in both sexes, including hypertension, hyperlipidemia, diabetes mellitus, smoking, and atrial fibrillation, there are several stroke risk factors that are specific to women. Specifically, differences in sex hormones, exogenous estrogens, and pregnancy exposures are factors exclusively experienced by females (2).
Guidelines for stroke in women
In 2014, the American Heart Association/American Stroke Association published the first guidelines that summarized data on stroke risk factors that are unique to and more common in women than men and expanded on the data provided in prior stroke guidelines and cardiovascular prevention guidelines for women. This guideline focused on the risk factors unique to women, such as reproductive factors, and those that are more common in women, including migraine with aura, obesity, metabolic syndrome, and atrial fibrillation (3).The authors concluded that prevention efforts for women would be enhanced if future epidemiological studies provided more detail on stroke subtype, especially hemorrhagic stroke, in addition to accounting for age and sex. Also, it was emphasized that improvement of stroke awareness and support of more rigorous education to women at younger ages is very important, including childbearing ages, because of women’s increased risk of stroke with age; the risks of stroke associated with pregnancy, gestational hypertension, and hormonal contraception; and the onset of stroke risk factors such as obesity, hypertension, and diabetes mellitus, which occur at younger ages.
In 2022, the European Stroke Organization published guidelines on stroke in women: Management of menopause, pregnancy and postpartum (4). Based on available evidence, recommendations or expert concensus statements were provided. Low quality of evidence was found to suggest against the use of HRT to reduce the risk of stroke (ischaemic and haemorrhagic) in postmenopausal women. No data was available on the outcome of women with stroke when treated with HRT. No sufficient evidence was found to provide recommendations for treatment with intravenous thrombolysis and mechanical thrombectomy during pregnancy, postpartum and menstruation. The majority of members suggested that pregnant women can be treated with IVT after assessing the benefit/risk profile on an individual basis, all members suggested treatment with IVT during postpartum and menstruation. All members suggested treatment with MT during pregnancy. The guidelines highlighted the need to identify evidence for stroke prevention and acute treatment in women in more vulnerable periods of their lifetime to generate reliable data for future guidelines.
Transgender women
The prevalence of transgender adults in the United States is estimated to be ≈0.5% of the population (5). Some transgender individuals receive hormonal therapy or sex-affirming surgery to assume secondary sex characteristics consistent with their sex identity. The use of certain hormonal therapies has implications for the incidence of stroke in these individuals (2). The Dutch study from 1997 found that 5.5% of trandgender women who were treated with ethinyl estradiol and the antiandrogen cyproterone acetate developed deep vein thrombosis or pulmonary embolism, 0.6% experienced a transient ischemic attack, and none experienced ischemic stroke (6). The Belgian study from 2013 reported that 5.1% of the transgender women who received estrogen therapy developed deep vein thrombosis or pulmonary embolism and 2.3% were diagnosed with transient ischemic attack or cerebrovascular disease during treatment (7). Another Dutch study from 2011 found no difference in the incidence of fatal stroke in transwomen compared with the incidence in the general population (8). So, transgender woman who have had a stroke should not be prescribed hormone therapy.
Conclusion
Clinicians should be aware of stroke risk factors that are specific to women and optimize primary and secondary prevention. Specific considerations should include endogenous hormone levels, exogenous hormone therapy, pregnancy and the peripartum period. Special attention and further research are needed in transgender females.
References
- Bushnell CD, Kapral MK. Stroke in Women and Unique Risk Factors. 2023https://doi.org/10.1161/STROKEAHA.122.041734Stroke. 2023;54:587–590
- Demel SL, Kittner S, Ley SH et al. Stroke Risk Factors Unique to Women. 2018https://doi.org/10.1161/STROKEAHA.117.018415Stroke. 2018;49:518–523
- Bushnell C, McCullough LD, Awad IA et al. and on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Council for High Blood Pressure Research. Guidelines for the Prevention of Stroke in Women. A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. 2014https://doi.org/10.1161/01.str.0000442009.06663.48Stroke. 2014;45:1545–1588
- Kremer C, Gdovinova Z, Bejot Y, Heldner MR, Zuurbier S, Walter S, Lal A, Epple C, Lorenzano S, Mono ML, Karapanayiotides T, Krishnan K, Jovanovic D, Dawson J, Caso V. European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum. Eur Stroke J. 2022 Jun;7(2):I-XIX. doi: 10.1177/23969873221078696. Epub 2022 Mar 29. PMID: 35647308; PMCID: PMC9134774.
- Crissman HP, Berger MB, Graham LF, Dalton VK. Transgender demographics: a household probability sample of US adults, 2014.Am J Public Health. 2017; 107:213–215. doi: 10.2105/AJPH.2016.303571.
- van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones.Clin Endocrinol (Oxf). 1997; 47:337–342.CrossrefMedlineGoogle Scholar
- Wierckx K, Elaut E, Declercq E, Heylens G, De Cuypere G, Taes Y, et al. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study.Eur J Endocrinol. 2013; 169:471–478. doi: 10.1530/EJE-13-0493.CrossrefMedlineGoogle Scholar
- Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.Eur J Endocrinol. 2011; 164:635–642. doi: 10.1530/EJE-10-1038.CrossrefMedlineGoogle Scholar
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