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Reproductive Endocrinology

ORF46-02 - Impact of Gender-Affirming Hormone Therapy on Lipid Parameters in AMAB Transgender Patients: The Pivotal Role of Antiandrogen Treatment

Monday, June 15, 2026
2:00 PM - 2:15 PM CT
Location: Room W179

Feminizing gender-affirming hormone therapy (GAHT) in AMAB (Assigned Male at Birth) individuals consists of estrogen therapy, optionally combined with antiandrogen agents, to promote the development of feminizing physical characteristics and reduce those typical of the sex assigned at birth. Current evidence regarding its impact on the lipid profile remains limited and inconclusive.
In this retrospective cross-sectional observational study, we evaluated the potential impact of GAHT on lipid parameters in 109 AMAB patients (156 measurements). Variables considered included estrogen formulation, serum estradiol levels, type of antiandrogen used, and serum testosterone levels, with age and BMI included as potential confounders.
Overall, lipid parameters were generally within the normal range, with lower rates of dyslipidemia compared with age-matched reference AMAB and AFAB populations.
In mixed-effects models adjusted for individual variability and confounders, estrogen formulation, as well as circulating estradiol and testosterone levels, did not appear to significantly affect the lipid profile. Use of cyproterone acetate (CPA) in combination with estrogens was associated with reductions in total cholesterol (-53.3%, P < 0.001), LDL cholesterol (-20 mg/dL, P = 0.043), and triglycerides (-53.3%, P < 0.001) compared with spironolactone, and with reductions in total cholesterol (-41.4%, P = 0.007), triglycerides (-41.5%, P = 0.007), and HDL cholesterol (-7.65 mg/dL, P = 0.031) compared with estrogen monotherapy. Analyses incorporating CPA dose suggested a dose-dependent reduction in all lipid parameters.
Overall, GAHT appears to be relatively safe for lipid metabolism. The choice of antiandrogen may be the component of GAHT with the most pronounced impact on the lipid profile, independently of its effect on testosterone levels. While acknowledging the complex effects on lipid metabolism and the potential reduction in HDL cholesterol, CPA may be associated with an overall more favorable lipid profile. Further longitudinal studies will be required to confirm these findings and to assess their association with long-term vascular outcomes.