Sex/gender medicine. The biological basis for personalized care in cardiovascular medicine

Abstract

Sex differences in morbidity and mortality associated with cardiovascular disease have been recognized by the medical community for decades. Investigation into the underlying biological basis of these differences was largely neglected by the scientific community until a report released by the Institute of Medicine in the United States in 2001 "Exploring the Biological Contributions to Human Health: Does Sex Matter?" Recommendations from this report included the need for more accurate use of the terms "sex" and "gender", better tools and resources to study the biological basis of sex differences, integration of findings from different levels of biological organization and continued synergy between basic and clinical researchers. Ten years after the Institute's report, this review evaluates some of the sex differences in cardiovascular disease, reviews new approaches to study sex differences and emphasizes areas where further research is required. In the era of personalized medicine, the study of the biological basis of sex differences promises to optimize preventive, diagnostic and therapeutic strategies for cardiovascular disease in men and women, but will require diligence by the scientific and medical communities to remember that sex does matter.

Figure 1

Schematic of autonomic reflexes influencing cardiovascular control. Every cell has a sex defined by the presence of XX or XY chromosomes. Transcription of genes on these chromosomes will affect the function of each component of the autonomic arch, including sensitivity of receptors, and neuronal transmission in the brain, spinal cord and effector organs. In addition, sex hormones (estrogen and testosterone) will regulate the expression of receptors for neurotransmitters, neuronal conductivity and functions of effector organs themselves, such as the content and release of vasoactive factors from the vascular endothelium, contractile elements and their calcium sensitivity in vascular and cardiac muscle, production of adrenergic transmitter and components of the renin–angiotensin system. The effect of genetic polymorphisms in adrenergic receptors on cardiovascular risk differentially segregate with genetic sex. α2, adrenergic receptor subtype; β1,2, adrenergic receptor subtypes; DOPA, dihydroxyphenylalanine; NE, norepinephrine; Y_Sry, gene locus on the Y chromosome.