Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender healthcare, yet its metabolic and cardiovascular effects remain under active investigation. Current evidence indicates changes in lipid profiles, body composition, and insulin sensitivity, with distinct patterns between masculinizing and feminizing regimens.
Masculinizing GAHT with testosterone in individuals assigned female at birth (AFAB) is associated with an atherogenic lipid profile, including increased LDL cholesterol and triglycerides and decreased HDL cholesterol. Blood pressure effects appear minimal, while body composition demonstrates increased lean mass and reduced fat mass. Insulin sensitivity remains stable or slightly improved, with no documented rise in type 2 diabetes incidence.
Feminizing GAHT with estrogens and antiandrogens produces less consistent results. Evidence highlights fat redistribution, with increased subcutaneous adipose tissue and reduced muscle mass. Some studies suggest higher insulin resistance, although diabetes incidence remains comparable to the general population. Thromboembolic and cerebrovascular risks persist, particularly with oral estrogens, whereas transdermal formulations appear safer.
Overall, while metabolic alterations are documented, current evidence does not establish a definitive increase in major cardiovascular events. Further prospective studies with larger, more diverse cohorts and longer follow-up are needed to clarify long-term outcomes and optimize GAHT safety and efficacy.