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Cardiometabolic benefits and risks for transgender youth with the initiation of gender-affirming hormone therapy: a case series

Stachenfeld NS, Leone CA, Weinzimer SA

Journal of applied physiology (Bethesda, Md. : 1985), 2026

Abstract

Interventions for transgender (TG) youth include puberty suppression and gender-affirming hormone therapy (GAHT). Studies have begun to show changes in cardiometabolic outcomes in adolescent transgender males (TGM) and females (TGF). We hypothesized that in TGM and TGF youth, GAHT would increase total cholesterol, low-density lipoprotein cholesterol, insulin resistance (IR), and adiposity while decreasing high-density lipoprotein cholesterol (HDL-C) and endothelium-dependent vasodilation. We measured IR (oral glucose tolerance test), lipid profile, and endothelial function (flow-mediated vasodilation) before and following 6 mo of GAHT in TGM (n = 3) and TGF (n = 2). This case series shows attenuated endothelium-mediated vasodilation in TGM, but improved endothelium-mediated vasodilation in TGF. Our data also support earlier findings showing reduced HDL-C with GAHT in TGM. Two of three TGMs showed increased IR, whereas one TGF showed decreased IR following GAHT. These data indicate rapid, but divergent, changes in lipids and endothelial function in TG youth with GAHT.NEW & NOTEWORTHY Although these data are preliminary, they show changes in FMD in transgender youth and suggest divergent responses, indicating attenuated FMD and lower HDL-C in males, whereas some improvement in endothelial function and little impact on lipids in females.

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Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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