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
ReviewSex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes
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
References (136)
- et al.
Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study)
Lancet
(2005) - et al.
Estrogen and ischemic neuroprotection: an integrated view
Trends Endocrinol Metab
(2003) - et al.
Metabolic syndrome and risk of cardiovascular disease: a meta-analysis
Am J Med
(2006) - et al.
Impact of the individual components of the metabolic syndrome and their different combinations on the prevalence of atherosclerotic vascular disease in type 2 diabetes: the Diabetes in Germany (DIG) study
Cardiovasc Diabetol
(2007) Haemostatic changes in pregnancy
Thromb Res
(2004)- et al.
Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study
Lancet Neurol
(2007) - et al.
Sex differences in stroke severity, symptoms, and deficits after first-ever ischemic stroke
J Stroke Cerebrovasc Dis
(2007) - et al.
Acute stroke: delays to presentation and emergency department evaluation
Ann Emerg Med
(1999) - et al.
Out-of-hospital delays in patients with acute stroke
Ann Emerg Med
(2004) Hong Kong patients' knowledge of stroke does not influence time-to-hospital presentation
J Clin Neurosci
(2001)
Lack of t-PA use for acute ischemic stroke in a community hospital: high incidence of exclusion criteria
Am J Emerg Med
Sources and reasons for delays in the care of acute stroke patients
J Neurol Sci
Sex and acute stroke presentation
Ann Emerg Med
Advancing the study of stroke in women—summary and recommendations for future research from an NINDS-sponsored multidisciplinary working group
Stroke
Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years
JAMA
Stroke in a biracial population: the excess burden of stroke among blacks
Stroke
Evidence for age-dependent education-related differences in men and women with first-ever stroke
Neuroepidemiology
Sex differences in management and outcome after stroke: a Swedish national perspective
Stroke
Sex differences and similarities in the management and outcome of stroke patients
Stroke
Sex differences in first-ever acute stroke
Stroke
Sex differences in stroke care and outcomes: results from the Registry of the Canadian Stroke Network
Stroke
Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry
Stroke
Influence of gender on baseline features and clinical outcomes among 17,370 patients with confirmed ischaemic stroke in the international stroke trial
Neuroepidemiology
Stable stroke incidence rates but improved case-fatality 06 in Dijon, France, from 1985 to 2004
Stroke
Effect of measurement on sex difference in stroke mortality
Stroke
Stroke incidence, case-fatality, and mortality in the WHO MONICA Project
Stroke
Sex-related time-dependent variations in post-stroke survival: evidence of a female stroke survival advantage
Neuroepidemiology
Prevalence of stroke—United States, 2005 [reprinted from MMWR Morb Mortal Wkly Rep 2007; 56: 469–74]
JAMA
The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study: objectives and design
Neuroepidemiology
Gender-linked brain injury in experimental stroke
Stroke
Postischemic estrogen reduces hypoperfusion and secondary ischemia after experimental stroke
Stroke
Influence of sex steroid hormones on cerebrovascular function
J Appl Physiol
Age and sex differences in cerebral hemodynamics: a transcranial Doppler study
Stroke
Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women
JAMA
A clinical trial of estrogen-replacement therapy after ischemic stroke
N Engl J Med
Effect of estrogen plus progestin on stroke in postmenopausal women—The Women's Health Initiative: a randomized trial
JAMA
Effects of conjugated equine estrogen on stroke in the Women's Health Initiative
Circulation
Hormone therapy to prevent disease and prolong life in postmenopausal women
Ann Intern Med
Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause [published erratum in JAMA 2008; 299: 1426]
JAMA
Cerebral microvessel responses to focal ischemia
J Cereb Blood Flow Metab
Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials
Stroke
Arterial occlusive lesions recanalize more frequently in women than in men after intravenous tissue plasminogen activator administration for acute stroke
Stroke
Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke
Neurology
Recanalization and outcome after intra-arterial thrombolysis in middle cerebral artery and internal carotid artery occlusion: does sex matter?
Stroke
Sex differences in stroke recovery
Prev Chronic Dis
Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council
Circulation
Diabetes and cardiovascular disease. The Framingham study
JAMA
The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up
Arch Intern Med
Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey
JAMA
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