Sex differences in stroke: Challenges and opportunities

Abstract

Biologic sex influences many variables that are important to brain health in general, and to stroke or cerebral ischemia in particular, such as general health status, cerebrovascular anatomy and function, unique risk factors such as pregnancy and preeclampsia, symptomatology, and therapeutic response. A more complete understanding of the scale and depth of sexual dimorphism in the brain and the role of more general sex-based factors is crucial to reducing the burden of stroke in women and men. This focused review highlights recent findings in stroke, including sex differences in epidemiology, risk factor reduction, comparative use of stroke therapeutics in both sexes, the importance of frailty in women, and the biologic basis for sex differences in stroke. Such findings show tremendous promise for the future of personalized medicine in stroke prevention and treatment.

Keywords: Sex; sex differences; stroke; women.

Figure 1.

The four-core-genotype (FCG) mouse model to determine the role of sex chromosomes in ischemic sensitivity and outcome. (a) Schematic of the generation of FCG mice in which the Sry gene (the testis-determining gene; sex-determining region, Y chromosome) is removed from the Y chromosome and inserted on an autosome (Chromosome 3). This produces XX and XY mice with testes, and XX and XY mice with ovaries, allowing for the independent assessment of the effects of sex chromosome complement. (b) PCR showing the presence of the Sry in XYM and XXM (gonadal males) and the absence of Sry in XXF and XYF (gonadal females). Ymt identifies the Y chromosome and Myo is used as a positive control.