Sex and Gender Shape Health—Time for Science to Establish Clarity
Published in Protocols & Methods, Research Data, and Biomedical Research
Our research team from the University of Toronto and the KITE Toronto Rehabilitation Institute, Canada, synthesized evidence from 19 observational studies involving more than 643,000 adults. Unlike previous reviews that focused on binary sex or gender categories, we examined measurable attributes of sex - such as hormone levels and polygenic scores - as well as gender identity, roles, and adherence to masculine or feminine norms, across 34 health outcomes. Our goal was to identify which aspects of sex and gender matter for clinical decision-making.
The evidence revealed clear sex-specific health effects. Testosterone, for instance, was linked to sexual and reproductive health, mental well-being, and certain cancers. However, differences between total and bioavailable testosterone highlight the urgent need for greater precision in measuring hormonal effects on health.
Our results also highlighted the critical role of gender norms. Adherence to masculine norms and stress from role discrepancies were linked to depression, anxiety, and cardiovascular risk in men. Research on feminine gender norms remains limited, reflecting a persistent androcentric bias in the evidence base. Addressing this gap is essential for advancing precision medicine and equitable health care.
Our results reinforce the importance of measuring attributes of sex and gender together. Health is shaped not only by physical and physiological traits but also by peoples' roles, norms, and social relationship. To make precision medicine effective for all, future scientific research must study sex and gender jointly, rather than treating them as separate or binary categories, recognizing the diversity of both biological traits and gender expression, and that health reflects the deeply interconnected effects of sex and gender.
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Biology of Sex Differences
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