Gender-affirming hormone therapy produces rapid but divergent cardiometabolic changes in transgender youth, with attenuated endothelium-mediated vasodilation and reduced HDL-C in transgender males, whereas transgender females showed improved endothelial function and little impact on lipids.
Key Findings
Results
Transgender male youth showed attenuated endothelium-mediated vasodilation following 6 months of gender-affirming hormone therapy.
Flow-mediated vasodilation (FMD) was used to measure endothelial function before and after GAHT
Sample consisted of 3 transgender males (TGM)
Measurements were taken at baseline and following 6 months of GAHT
The finding aligns with the authors' hypothesis that GAHT would decrease endothelium-dependent vasodilation in TGM
Results
Transgender female youth showed improved endothelium-mediated vasodilation following 6 months of gender-affirming hormone therapy.
Sample consisted of 2 transgender females (TGF)
This finding was divergent from the response seen in transgender males
Authors described this as an improvement in endothelial function
The result was contrary to the authors' initial hypothesis that GAHT would decrease endothelium-dependent vasodilation across TG youth
Results
Transgender male youth showed reduced HDL-C (high-density lipoprotein cholesterol) following gender-affirming hormone therapy.
Lipid profiles were measured before and after 6 months of GAHT
Reduced HDL-C in TGM is described as supporting 'earlier findings' in the literature
Transgender females showed 'little impact on lipids' following GAHT
Full lipid profiles including total cholesterol and LDL-C were measured as part of the study protocol
Results
Two of three transgender male youth showed increased insulin resistance following 6 months of gender-affirming hormone therapy.
Insulin resistance (IR) was measured using an oral glucose tolerance test (OGTT)
2 out of 3 TGMs demonstrated increased IR after GAHT
One transgender female showed decreased IR following GAHT
The remaining participants' IR outcomes were not described as notable changes in the abstract
Results
The cardiometabolic changes observed with gender-affirming hormone therapy in transgender youth were characterized as rapid and divergent between transgender males and females.
Changes were observed within 6 months of initiating GAHT
Authors describe responses as 'divergent,' with opposing directions of effect for endothelial function between TGM and TGF
Authors note these data are 'preliminary' given the small case series design (n=5 total: 3 TGM, 2 TGF)
Outcomes measured included insulin resistance, lipid profile, and flow-mediated vasodilation
What This Means
This research suggests that hormone therapy used in gender-affirming care for transgender youth causes measurable changes in heart and metabolic health within just six months of starting treatment, but those changes differ depending on whether a young person is a transgender male or transgender female. In transgender males (those assigned female at birth who are treated with testosterone), the study found that blood vessels became less able to expand normally—a measure of vascular health called flow-mediated vasodilation—and that 'good' cholesterol (HDL-C) levels dropped. Two of the three transgender males also showed signs of increased insulin resistance, which is a risk factor for type 2 diabetes. In contrast, the two transgender females studied (those assigned male at birth who are treated with estrogen) showed improved blood vessel function and minimal changes in cholesterol or insulin resistance.
This was a small case series of only five participants, so the findings should be interpreted with caution and are described by the authors themselves as preliminary. The study adds to a growing but limited body of research examining how gender-affirming hormone therapy affects physical health in adolescents. The divergent findings between transgender males and females suggest that the type of hormone therapy matters when thinking about potential cardiovascular and metabolic effects.
This research suggests that healthcare providers working with transgender youth may want to monitor cardiometabolic markers such as cholesterol levels, blood vessel function, and insulin sensitivity after initiating hormone therapy, particularly in transgender males. Larger studies will be needed to confirm these findings and better understand the long-term implications for cardiovascular and metabolic health in this population.
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Stachenfeld N, Leone C, Weinzimer S. (2026). Cardiometabolic benefits and risks for transgender youth with the initiation of gender-affirming hormone therapy: a case series.. Journal of applied physiology (Bethesda, Md. : 1985). https://doi.org/10.1152/japplphysiol.00519.2026