Cardiometabolic Risk in Transgender Individuals: Effects of Hormones and Chromosomes
Overview
This study evaluated cardiometabolic risk biomarkers and vascular function in transgender men and women undergoing gender-affirming hormone therapy. Findings indicate increased cardiometabolic risk in transgender men, including proatherogenic lipoprotein changes and elevated diabetes risk markers, while transgender women showed early beneficial changes. Sex chromosomes had fewer intrinsic effects, though XY individuals exhibited higher apparent diabetes risk.
Background
Transgender individuals represent a growing population seeking gender-affirming hormone therapy, yet the impact of sex hormones and chromosomes on cardiometabolic risk remains incompletely understood. Cardiometabolic disease is the leading cause of mortality worldwide and exhibits sex-specific traits, making it critical to understand these mechanisms in transgender populations. Prior studies have shown mixed results regarding cardiovascular and diabetes risk in transgender individuals, often limited by confounding factors and lack of validated risk prediction tools. This study aimed to clarify the effects of hormone therapy and chromosomal sex on a comprehensive panel of cardiometabolic biomarkers and vascular function.
Data Highlights
Parameter
Transgender Men
Transgender Women
Significance
Systolic Blood Pressure
Increased (P = .002)
No significant change
Lipoprotein Profile
Proatherogenic changes
Tended to improve with estrogen
Diabetes Risk Metabolites (e.g., plasma glucose)
Increased (P = .025)
Decreased (P = .002)
Cholesterol Efflux Capacity (CEC)
Unchanged
Decreased (P < .01)
Association of ApoA-1 with CEC
Lost at 11 months
Lost at 11 months
Diabetes Risk by Chromosome
Higher in XY vs XX at 4 weeks (P = .002)
Key Findings
Transgender men developed a proatherogenic lipoprotein profile and increased systolic blood pressure after hormone therapy.
Transgender women showed early improvements in lipoprotein profiles with estrogen treatment but experienced decreased cholesterol efflux capacity.
Markers indicative of increased diabetes risk, including plasma glucose, rose in transgender men but decreased in transgender women.
At 4 weeks post-gonadal suppression, individuals with XY chromosomes had higher apparent diabetes risk compared to XX individuals.
The strong positive correlation between apolipoprotein A-1 and cholesterol efflux capacity observed at baseline was lost in both groups after 11 months of hormone therapy.
Clinical Implications
Clinicians should recognize that transgender men may experience increased cardiometabolic risk, including adverse lipid changes and elevated diabetes risk markers, necessitating careful monitoring during hormone therapy. Transgender women may benefit from early improvements in lipid profiles but require assessment of cholesterol efflux capacity and other cardiovascular parameters. Sex chromosome complement appears to have a lesser impact but may influence diabetes risk, underscoring the need for individualized risk evaluation in transgender care.
Conclusion
Gender-affirming hormone therapy induces distinct cardiometabolic changes in transgender men and women, with increased risk markers in transgender men and early beneficial effects in transgender women. Further research is essential to refine risk prediction and optimize cardiovascular care in transgender populations.
References
GETS Study Group 2024 -- Evaluating Cardiometabolic Risk in Transgender Populations
