Sex differences in cardiometabolic diseases such as diabetes, non-alcoholic fatty liver disease (NAFLD), coronary artery disease (CAD) and heart failure have been amply described in mice, humans, and other species, with premenopausal females generally exhibiting more beneficial metabolic profiles. For example, NAFLD is more prevalent in males than females before menopause, with males exhibiting severe NAFLD symptoms. Similarly, men develop CAD at an earlier age than women and there is a substantial increase in CAD following menopause. Also, the frequency of heart failure with preserved ejection fraction is about twice as high in women as men. These differences are yet not understood.
While originally those differences were attributed to the effect of sex hormones, recent studies suggest that both hormones and sex chromosome complement play a role. The effects of sex hormones can be either reversible or irreversible (‘organizational’). Sex differences may be dependent upon the genetic background, environmental factors, and the gut microbiome. Mitochondrial traits including mitochondrial gene expression, oxidative phosphorylation, and UCP1-mediated adaptive thermogenesis have also been implicated in sex differences. Clearly, an understanding of the genetic, environmental, hormonal, mitochondrial and chromosomal factors involved in sex differences could reveal novel targets for treatment and would be helpful for sex-specific diagnosis and prevention strategies enabling the development of personalized medicine.
Sex differences in cardiometabolic diseases such as diabetes, non-alcoholic fatty liver disease (NAFLD), coronary artery disease (CAD) and heart failure have been amply described in mice, humans, and other species, with premenopausal females generally exhibiting more beneficial metabolic profiles. For example, NAFLD is more prevalent in males than females before menopause, with males exhibiting severe NAFLD symptoms. Similarly, men develop CAD at an earlier age than women and there is a substantial increase in CAD following menopause. Also, the frequency of heart failure with preserved ejection fraction is about twice as high in women as men. These differences are yet not understood.
While originally those differences were attributed to the effect of sex hormones, recent studies suggest that both hormones and sex chromosome complement play a role. The effects of sex hormones can be either reversible or irreversible (‘organizational’). Sex differences may be dependent upon the genetic background, environmental factors, and the gut microbiome. Mitochondrial traits including mitochondrial gene expression, oxidative phosphorylation, and UCP1-mediated adaptive thermogenesis have also been implicated in sex differences. Clearly, an understanding of the genetic, environmental, hormonal, mitochondrial and chromosomal factors involved in sex differences could reveal novel targets for treatment and would be helpful for sex-specific diagnosis and prevention strategies enabling the development of personalized medicine.