Elsevier

The Lancet Neurology

Volume 7, Issue 10, October 2008, Pages 915-926
The Lancet Neurology

Review
Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes

https://doi.org/10.1016/S1474-4422(08)70193-5Get rights and content

Summary

Stroke has a greater effect on women than men because women have more events and are less likely to recover. Age-specific stroke rates are higher in men, but, because of their longer life expectancy and much higher incidence at older ages, women have more stroke events than men. With the exception of subarachnoid haemorrhage, there is little evidence of sex differences in stroke subtype or severity. Although several reports found that women are less likely to receive some in-hospital interventions, most differences disappear after age and comorbidities are accounted for. However, sex disparities persist in the use of thrombolytic treatment (with alteplase) and lipid testing. Functional outcomes and quality of life after stroke are consistently poorer in women, despite adjustment for baseline differences in age, prestroke function, and comorbidities. Here, we comprehensively review the epidemiology, clinical presentation, medical care, and outcomes of stroke in women.

Introduction

There is growing recognition of the clinical and public health importance of stroke in women.1 Although age-specific stroke incidence and mortality rates are higher in men than in women, stroke affects a greater number of women because of their increased longevity and the fact that stroke event rates increase substantially in the oldest age groups. Moreover, stroke-related outcomes, including disability and quality of life (QOL), are consistently poorer in women than in men, yet the reasons for this are not well understood. The societal impact of poor stroke outcomes in women is compounded by the fact that elderly women are much more likely to live alone and to be socially isolated.

The importance of the differential effect of stroke on women will continue to grow over subsequent decades as an increasingly older population results in an ever greater number of stroke events in women. Because of this oncoming epidemic, the stroke community needs to address the underlying biological, epidemiological, and clinical causes and manifestations of stroke in women. Our aim is to provide a comprehensive review of the published literature on sex differences in stroke, with specific emphasis on the epidemiology, clinical presentation, medical care, and outcomes. In turn, we hope to raise awareness of the important sex differences in stroke, and to identify priority areas for further research.

Section snippets

Mortality

Between 1999 and 2004, the US age-adjusted (year 2000 standard) stroke mortality rate was about 3% lower in white women aged over 25 years (82·4 per 100 000) than in white men (84·8 per 100 000), and 13% lower in black women (111·1 per 100 000) than in black men (128·3 per 100 000; data from the Centers for Disease Control and Prevention WONDER database). However, these sex differences are strongly modified by age (figure 1). Below the age of 45 years, stroke mortality for women and men is

Biological origins for sex differences in stroke

The most common biological explanation for sex differences in stroke is related to sex steroid hormones, particularly oestrogen. This hypothesis is supported by robust sex differences in animal models of ischaemic stroke. For example, after middle cerebral artery occlusion in rodents, females have smaller stroke volumes than have males. However, ovariectomised females have similar stroke volumes to males, whereas volumes in ovariectomised females given oestrogen replacement are similar to

Clinical characteristics at stroke onset

At least two studies have shown that women have worse prestroke disability than men.11, 35 Women are also more likely to be living alone or to be in an assisted living arrangement or a nursing home before their stroke event.7, 11, 35 Men and women with stroke differ with respect to the prevalence of stroke risk factors. Women with stroke are older at onset (by an average of about 4 years), and are more likely to have atrial fibrillation and hypertension, whereas men with stroke are more likely

Prehospital and in-hospital delays

Many studies have been undertaken in several countries to identify factors that are associated with the time from stroke onset to arrival in the emergency department (ie, prehospital delay). Nearly all of these studies have found no evidence of clinically important differences in prehospital delay between women and men.10, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 Among the few studies that did find evidence of sex differences in prehospital delay, five found that women

In-hospital diagnostic and treatment procedures

Relatively few studies have examined whether sex differences exist in the care of patients with acute stroke. Although some studies have found evidence of differences in the use of specific diagnostic and treatment-related procedures,11, 60, 92, 93, 94, 95 overall the number and magnitude of these differences has been relatively small, indicating that there are not major sex differences in the quality of in-hospital care. However, a European study found that women were less likely to receive

Sex differences in stroke preventive care

There are several sex differences relevant to antiplatelet treatment that are of potential clinical importance. Sex hormones have a differential effect on platelet function, with testosterone promoting platelet activity and oestrogen inhibiting it.109, 110 Sex differences in the pharmacology of aspirin, including absorption, bio-availability, and anti-inflammatory and antiplatelet effects,111, 112 suggest the possibility of sex-specific effects of aspirin in the prevention of stroke. However,

Functional outcomes and quality of life

Surprisingly few studies have been done with the primary objective of examining sex differences in functional outcomes after stroke. Published studies (table) include those from Europe7, 9, 11, 12, 128 and North America.10, 35, 106, 129 A consistent feature of these studies is that women have less favourable outcomes after stroke than do men. Women have more physical impairments and limitations in activities of daily living (ADL), as measured by the Barthel index.10, 11, 35, 106, 129 A European

Rehabilitation and post-stroke recovery

In the USA and elsewhere, women are less likely to be discharged home and are more likely to be discharged to nursing homes and long-term care after a stroke.7, 8, 10, 11, 12, 129, 135 In Canada, Europe, and the USA, there seem to be no differences in access to physical therapy, speech therapy, or occupational therapy for men and women.8, 10, 135 Although women have equal access to rehabilitation services, they do not experience the same levels of recovery.8, 10, 11, 135 In the only study that

Conclusions and future research

The sex differences in stroke can be summarised as follows: women have more stroke events due to their longer life expectancy and older age at the time of stroke onset. Women with stroke have a higher prevalence of hypertension, atrial fibrillation, and prestroke disability, but have a lower prevalence of heart disease, peripheral vascular disease, and smoking and alcohol use. Women with stroke are less likely to receive intravenous alteplase treatment and lipid testing while in hospital, and

Search strategy and selection criteria

After searching their own files, each section author did their own MEDLINE search to identify relevant papers with a set of core MeSH terms (“cerebrovascular accident”, “stroke”, “sex”, “sex factors”, “sex ratio”, and “sex distribution”), and with terms relevant to each particular topic. For example, the search string “treatment delay*[tiab] OR triage OR time factors” was used to find time-related or treatment-delay-related papers. The full list of search terms is available from the

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