The Importance of Considering Sex Differences in Translational Stroke Research

Abstract

Stroke is the second leading cause of death worldwide, and differences between men and women have been documented in incidence, prevalence, and outcome. Here, we reviewed the literature on sex differences in stroke severity, mortality, functional outcome, and response to therapies after ischemic stroke. Many of the sex differences in stroke severity and mortality are explained by differences in baseline demographics such as older age in women. However, women account for more stroke deaths, consistently suffer from worse stroke outcomes, and are more often institutionalized and permanently disabled than men. These sex differences in functional outcome are equalized after treatment with tissue plasminogen activator (tPA) and women may benefit more from treatment than men. However, this may depend on race, as African-American women have less of a response to tPA than other groups. Regarding endovascular treatments, the few existing studies that have investigated sex differences in stroke outcome point to equal benefit in both sexes; however, many clinical trials are relatively underpowered to detect sex differences. Further, we considered sex-specific effects in animal models of stroke and present recommendations for the performance of stroke studies in female animals. The male-biased use of research animals is distinguished from the clinical situation where there is a disproportionate and growing female stroke population. Stroke in women is greatly understudied, and including both sexes is especially important in both preclinical and clinical studies that evaluate potential stroke therapies.

Keywords: Estrogen; Sex differences; Stroke; Tissue plasminogen activator; Translational.