Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes

Abstract

Despite a growing body of evidence, the distinct contributions of biological sex and the sociocultural dimension of gender to the manifestations and outcomes of ischaemic heart disease and heart failure remain unknown. The intertwining of sex-based differences in genetic and hormonal mechanisms with the complex dimension of gender and its different components and determinants that result in different disease phenotypes in women and men needs to be elucidated. The relative contribution of purely biological factors, such as genes and hormones, to cardiovascular phenotypes and outcomes is not yet fully understood. Increasing awareness of the effects of gender has led to efforts to measure gender in retrospective and prospective clinical studies and the development of gender scores. However, the synergistic or opposing effects of sex and gender on cardiovascular traits and on ischaemic heart disease and heart failure mechanisms have not yet been systematically described. Furthermore, specific considerations of sex-related and gender-related factors in gender dysphoria or in heart-brain interactions and their association with cardiovascular disease are still lacking. In this Review, we summarize contemporary evidence on the distinct effects of sex and gender as well as of their interactions on cardiovascular disease and how they favourably or unfavourably influence the pathogenesis, clinical manifestations and treatment responses in patients with ischaemic heart disease or heart failure.

Fig. 1. Concepts of sex and gender in medicine.

Health and disease are influenced by biological sex factors (genes and sex hormones) and sociocultural gender factors that interact with and modify each other.

Fig. 2. Interactions between sex and gender in health and disease throughout the life cycle.

Sex chromosomes and sex hormones are active throughout the entire life cycle, starting in germ cells and continuing in the embryo, fetus, child, adult, and aged and diseased individual. Biological factors interact with the sociocultural dimension of gender (including psychological attributes, the physical and social environment, and lifestyle) at all stages of the life course. Adapted with permission from ref..

Fig. 3. Gender score distribution in females and males in an aged German population.

The graph shows the distribution of a retrospective gender score, which included gender-related factors, such as education, income, household activity and stress, according to biological sex in a population of German individuals with a mean age of 75.6 years. A score of 0 represents individuals who have only masculine characteristics, whereas 100 represents an individual with only feminine characteristics. The data show that male individuals have a lower gender score (have more masculine characteristics) whereas female individuals have higher scores (have more feminine characteristics) yet both have masculine and feminine traits. Adapted with permission from ref..

Fig. 4. Sex-related and gender-related disparities in CVD risk and outcomes.

a, Factors contributing to sex-related and gender-related modulation of cardiovascular disease (CVD) risk and outcomes in women and men. b, Factors associated with positive or negative CVD outcomes in women and men. CAD, coronary artery disease; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HRQoL, health-related quality of life; ICU, intensive care unit.