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Abstract
Gender- and Sex-Conscious Medicine (GSCM) represents a critical and emerging paradigm in clinical practice and biomedical research. Biological sex is defined by chromosomal complement, gonadal structure, reproductive anatomy and circulating sex steroid profiles— In contrast, gender identity—the subjective experience of gender may encompass masculine, feminine, nonbinary, or other identities and is primarily self – defined and a sociocultural
construct with considerable variability.
Both sex (biological attributes) and gender (psychosocial context) exert profound effects on the physiology and pathophysiology of organ systems, influencing disease susceptibility, clinical presentation, progression, and outcomes. These factors also modulate pharmacokinetics and pharmacodynamics, such that individuals of different sexes and genders may respond differently to the same diagnostic and therapeutic interventions. Despite this, the majority of preclinical studies and clinical trials historically enrolled predominantly male subjects, resulting in an evidence base that is inadequately sex- and gender-disaggregated.
Consequently, sex- and gender-related disparities in diagnosis, treatment response, adverse events, and health outcomes persist—an inequity that is both an ethical concern and a substantial socioeconomic burden. Estimates suggest that removing this “health gap” could add at least US$1 trillion annually to global GDP by 2040.
In this review, we present physiological, pathophysiological, and clinical examples that illustrate the necessity of integrating sex- and gender-conscious approaches into research, teaching, guideline development, and clinical care. Although we acknowledge the continuum of gender identities, for analytic clarity this review uses binary male and female classifications. The clinical care and health concerns of sexual and gender minorities (LGBTQ +) constitute a distinct field—sexual and gender minority health. A comprehensive treatment of that topic is beyond the scope of the present review and would require a separate focused review.