Sex differences in incidence, pathophysiology, and outcome of primary intracerebral hemorrhage.

P rimary intracerebral hemorrhage (ICH) is a common, yet devastating, stroke subtype. Although ethnicity and age can predispose individuals to ICH and affect outcome, little investigation has been made into investigating sex differences in incidence, pathophysiology, or outcome after ICH. In order to understand fundamental mechanisms, improve preclinical research models, and develop effective treatment options for patients with ICH, assessing the effects of sex in ICH is imperative. Thus, the purpose of this review is to gather available information on incidence, pathophysiology, outcome, and pre-clinical study to provide basis for further investigations. Comprehensive literature search of Medline and National Library of Medicine (PubMed) publications was performed (last accessed December 1, 2013) using ICH, gender, sex, gender difference, sex difference, race, stroke, mortality, preclini-cal model, animal model, and neuroprotection as keywords. Articles in English were fully reviewed and included if clear definition of primary ICH and available sex data were reported. Primary ICH was defined as intraparenchymal hemorrhage not because of trauma or underlying structural lesion, for example, aneurysm, tumor, and so on. A total of 73 articles were included: (1) epidemiological studies assessing incidence and outcome (47 articles); (2) hospital-based studies assessing hematoma characteristics, treatment response, ICH-related complications or goals of care (14 articles); and (3) preclinical studies assessing gonadal hormones effects on ICH outcomes (12 articles). Published data are reported in chronological and geographical manner. Significant P values, relative risk (RR), odds ratios (OR), and confidence intervals (CI) are noted when available. Notably, epidemiological stroke studies generally treat ICH as a stroke subtype. Further, African and Indian population studies were absent from the literature. Over the last few decades, incidence of primary ICH in developed countries is unchanged or, perhaps, decreasing. 4–8 Decreasing incidence may be attributable to greater public awareness of preventive measures, such as healthy lifestyle and control of hypertension. In meta-analysis of 17 epidemiological studies, higher overall ICH incidence was noted in men (RR=1.60, 95% CI=1.47–1.74). 9 However, sex differences are not straightforward because interaction of sex, ethnicity, and age may influence incidence (Table 1). 21 and Turkey 22 have not demonstrated sex differences in overall ICH incidence. Two exceptions with male predisposition are from Greece 23 and Norway. 24 Notably, all but 4 of these studies were conducted on populations before 2000, all but 2 studies treated ICH as a stroke subtype of a total stroke population, and only 3 studies included a cohort of …