J Stroke.  2023 Jan;25(1):16-25. 10.5853/jos.2022.04077.

Sex and Gender Differences in Stroke and Their Practical Implications in Acute Care

• Ospel J
• Singh N
• Ganesh A
• Goyal M

• KMID: 2539055
• DOI: http://doi.org/10.5853/jos.2022.04077

Abstract

There are several controversies regarding the role of sex and gender in the pathophysiology and management of acute stroke. Assessing the role of sex, i.e., biological/pathophysiological factors, and gender, i.e., sociocultural factors, in isolation is often not possible since they are closely intertwined with each other. To complicate matters even more, the functional baseline status of women and men at the time of their first stroke is substantially different, whereby women have, on average, a poorer reported/ascertained baseline function compared to men. These differences in baseline variables account for a large part of the differences in post-stroke outcomes between women and men. Adjusting for these baseline differences is difficult, and in many cases, residual confounding cannot be excluded. Despite these obstacles, a better understanding of how patient sex and gender differences influence acute stroke and stroke care pathways is crucial to avoid biases and allow us to provide the best possible care for all acute stroke patients. Disregarding patient sex and gender on one hand and ignoring potential confounding factors in sex- and gender-stratified analyses on the other hand, may cause researchers to come to erroneous conclusions and physicians to provide suboptimal care. This review outlines sex- and gender-related factors in key aspects of acute stroke, including acute stroke epidemiology, diagnosis, access to care, treatment outcomes, and post-acute care. We also attempt to outline knowledge gaps, which deserve to be studied in further detail, and practical implications for physicians treating acute stroke patients in their daily practice.

Keyword

Stroke; Sex; Gender; Thromectomy; Thrombolysis; Outcomes

Figure

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  Figure 1. Illustration of key sex- and gender-related differences in stroke patients’ baseline status.

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  Figure 2. Sex- and gender-related factors in endovascular stroke treatment and intravenous thrombolysis. The yellow box illustrates societal (gender-related) factors that influence the treatment decision. The blue box illustrates biological (sex-related) factors that influence the treatment decision. Note that the inter-relationship between these variables is complex, whereby various societal factors influence each other, and the same is true for biological factors. There are also inter-relationships between societal and biological factors, as indicated by the dashed arrows. Also, note that this illustration merely points out exemplary inter-relationships between these factors and is not providing a comprehensive summary of all possible interactions and inter-relationships. To come to a treatment decision, there are access barriers (can the patient make contact with the healthcare system?), diagnostic challenges (are the acute ischemic stroke [AIS] symptoms recognized as such, and the correct diagnosis is made?) and decision challenges (should treatment be initiated, given the patient’s baseline status?) need to be overcome before treatment with endovascular treatment (EVT) or intravenous thrombolysis (IVT) is initiated. Based on all available evidence, neither EVT nor IVT treatment effect is modified based on sex. If treatment is initiated, current evidence suggests that women will sustain overall more post-stroke disability. However, they also benefit from a greater gain in disability-free life years compared to men.

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  Figure 3. Exclusion criteria in clinical trials and their effect on the representativeness of the female and male stroke patient population. The blue circle shows the entity of male stroke patients and the red circle shows the entity of female stroke patients on a population level. The x-axis indicates patient age at stroke onset, while the y-axis indicates pre-stroke disability at stroke onset. Since female stroke patients are on average older and suffer from more severe pre-stroke disability compared to males, applying an upper age limit and pre-stroke disability cap as part of clinical trial enrolment criteria disproportionately excludes females from the study. Even if an equal number of males and females of similar ages are included in the study, the female patients in the study will not be sufficiently representative of the general female stroke population. mRS, modified Rankin Scale.

Reference

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