Bridging the gap: Time to integrate sex and gender differences into research and clinical practice for improved health outcomes

The integration of sex and gender in medical research and clinical practice is increasingly recognized as a cornerstone for achieving equitable health outcomes. Biological sex and gender influence the manifestation, progression, and treatment response in numerous diseases. Biological sex influences health and disease outcomes through genetic, hormonal, and physiological factors, while gender impacts them via identity, societal roles and behaviors. Historically, medical research has focused predominantly on the male body, leading to diagnostic and therapeutic gaps for women and gender-diverse populations. In particular, women remain underrepresented in clinical trials, leading to suboptimal treatment strategies and outcomes. In addition, in many conditions, such as cardiovascular, metabolic and neurological diseases, sex-specific variations in risk factors and disease presentation are prominent. The present review discusses the critical importance of distinguishing between sex and gender in preclinical and clinical research, and the necessity of incorporating these variables across all stages of research, from study design to analysis and reporting of preclinical studies and clinical trials. By incorporating sex and gender as distinct but interacting variables, we propose a framework to advance health equity and foster personalized, inclusive healthcare. This approach will promote the development of gender-sensitive clinical guidelines, enhance the accuracy of diagnostic tools, and ultimately contribute to improved health outcomes for all individuals, regardless of their sex or gender identity.