Cardiometabolic Risk Assessment in Transgender Individuals-Differential Effect of Sex Hormones and Sex Chromosomes

While transgender individuals represent a substantial group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood.

The present study aimed to characterize the effect of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.

A total of 17 transgender men and 17 transgender women were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness and arterial stiffness, lipoproteins, and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and high-density lipoprotein-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the effect of sex hormones, comparisons of genetic XX and XY individuals at T1 the effect of sex chromosomes.

Vascular function was comparable at T12 and T0; systolic blood pressure increased in transgender men (P = .002). Transgender men developed a proatherogenic lipoprotein profile; estrogen treatment in transgender women tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transgender men (P = .025), with opposite changes in transgender women (P = .002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (P = .002). CEC decreased in transgender women (P < .01), while remaining unchanged in transgender men. However, in both groups the strong positive association of apolipoprotein A-1 with cholesterol efflux observed at T0 was lost at T12.

The results are consistent with increased cardiometabolic risk in transgender men, while transgender women show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have fewer intrinsic effects. XY individuals and transgender men display an increased apparent diabetes risk. Further research on cardiometabolic risk is needed for transgender individuals.