Menopause Live - IMS Updates

Date of release: 17 March, 2014

Primary prevention of stroke in women

Stroke is a major disease in women, having a huge impact on morbidity, mortality and health-care expenditure. Undoubtedly, it is related to aging and occurs mainly in old people, but does it have any gender-specific characteristics? A new guideline from the American Heart Association/American Stroke Association focuses 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 [1]. The document provides current evidence, research gaps, and recommendations on risk of stroke related to pre-eclampsia, oral contraceptives, menopause, and hormone replacement, as well as those risk factors more common in women. The conclusion of the guideline points at the need to more accurately reflect the risk of stroke in women across the lifespan, and perhaps even create a female-specific stroke risk score.


Perhaps our member gynecologists would wish to read the guideline sections which discuss pregnancy, pre-eclampsia and contraceptives in regard to the risk for stroke and the long-term need to carefully monitor subsets of women when appropriate [1]. However, the following commentary focuses on the relevance of menopause, hormone replacement therapy and metabolic risk parameters. The main problem is, of course, that the basal incidence of stroke in the peri- and early postmenopausal period is very small, and thus any attempt to get good quality information lies in the ability to collect data from a very large cohort. In fact, there have been only few such sources of information, which explains why it is impossible to reach clear-cut conclusions and produce relevant recommendations for prevention of stroke in mid-life women. Nevertheless, results of existing studies on the association between age at menopause or premature or early menopause, whether natural or surgical, and stroke risk appear to suggest increased risk of stroke with earlier onset of menopause, although the evidence is not entirely consistent [2]. Few data on the association of other surrogate markers for endogenous hormone exposures, such as lifetime estrogen exposure, duration of ovarian activity, or time since menopause, and stroke risk exist. Henderson and Lobo, who summarized the data recently [3], concluded that 'Stroke risk is not modified by age of hormone initiation or use, or by temporal proximity to menopause, and is similar for estrogen plus progestogen and for unopposed estrogen. Limited evidence implies that lower doses of transdermal estradiol (≤ 50 μg/day) may not alter stroke risk. For women less than 60 years of age, the absolute risk of stroke from standard-dose hormone therapy is rare, about two additional strokes per 10,000 person-years of use; the absolute risk is considerably greater for older women.'
What are the other gender-specific risk factors for stroke? It is well known that women with a migraine history, especially migraine with aura, have a higher risk for stroke in later life (including the hemorrhagic type). According to the Women’s Health Study data, the absolute risk of migraine-associated stroke is relatively low. Migraine with aura accounted for four additional ischemic stroke cases per 10,000 women per year [4]. Could we prevent stroke by effective treatment of migraine? It appears that there are not sufficient data to recommend specific approaches to treat migraine with the intention of lowering risk of stroke [1]. Another potential measure to prevent strokes would be a better control of the well-known cardiovascular risk factors. Such strategies seem to work well for the prevention of coronary artery disease. Is this true also in regard to stroke prevention in women? Obesity affects stroke risk in both men and women to the same extent, even after adjustment for factors such as age, physical activity, smoking, alcohol consumption, and co-morbid conditions such as hypertension and diabetes mellitus [5]. Needless to say that aiming at lowering blood pressure to the ideal values set by clinical guidelines is mandatory in hypertensive women, since high blood pressure is a major risk factor for stroke. Furthermore, it is logical to assume that a tight control of any cardiovascular metabolic risk factor and addressing key lifestyle parameters, such as a healthy diet, physical activity and weight, would lower the risk for stroke. As for primary prevention by medications, aspirin significantly lowers the risk for ischemic stroke in women (unlike in men), and therefore should be prescribed in women with a high stroke risk score, i.e. > 10% risk for cerebrovascular events during the next 10 years [6].
While health-care providers and the public are well aware of the preventive strategies to reduce the incidence of coronary artery disease, the guidance on prevention of stroke is somewhat lacking. The reason for that is probably the bundling of coronary artery disease with cerebrovascular disease, namely applying the same measures to both cardiovascular diseases. While this is basically right, the review and guideline that was published recently on behalf of several major US societies [1] highlights some important gender differences that should be considered while focusing on primary prevention of stroke in women.

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014 Feb 6. Epub ahead of print

  2. Rocca WA, Grossardt BR, Miller VM, Shuster LT, Brown RD Jr. Premature menopause or early menopause and risk of ischemic stroke. Menopause 2012;19:272-7

  3. Henderson VW, Lobo RA. Hormone therapy and the risk of stroke: perspectives 10 years after the Womens Health Initiative trials. Climacteric 2012;15:22934

  4. Kurth T, Diener HC. Migraine and stroke: perspectives for stroke physicians. Stroke 2012;43:34216

  5. Kurth T, Gaziano JM, Rexrode KM. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation 2005;111:19928

  6. Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006;295:30613