Prospective Short‐ and Long‐Term Changes in Cardiometabolic Risk Markers Following Gender‐Affirming Hormone Therapy

INTRODUCTION: Gender-affirming hormone therapy (GAHT) may be associated with increased cardiometabolic disease (CMD) risk. Prospective CMD risk screening is recommended, but long-term data are needed regarding changes in CMD markers. OBJECTIVES: To evaluate prospective changes in CMD risk markers during GAHT. METHODS: Transgender persons initiating (GAHT naïve) or on current GAHT (GAHT ongoing) were included in a 36-month prospective study at a Danish gender identity clinic. Participants were categorized as transmasculine (TransM, N = 245: GAHT naïve, N = 129, ongoing, N = 116) and transfeminine (TransF, N = 250: GAHT naïve, N = 157, ongoing, N = 93) persons. BMI, waist-hip-ratio, lipids, blood pressure (BP), and HbA1c were measured annually. RESULTS: In TransM, the baseline median age (interquartile range) was 23 (20-28) years in GAHT naïve and 25 (21-29) years in GAHT ongoing with median GAHT duration of 3.1 years. Masculinizing GAHT up to 36 months in GAHT naïve and ongoing TransM (N = 84) was associated with increased LDL and triglycerides, whereas GAHT naïve TransM (N = 53) in addition developed significantly increased waist, and HbA1c and decreased HDL. In TransF, the median age at baseline was 25 (22-30) years in GAHT naïve and 27 (23-36) years in GAHT ongoing with GAHT duration of median 2.2 years. In GAHT naïve, 36 months of feminizing GAHT (N = 38) was associated with increased weight, BMI, waist and hip and decreased total cholesterol and triglycerides, whereas CMD risk markers were unchanged in TransF GAHT ongoing. CONCLUSION: Masculinizing GAHT was predominantly associated with long-term adverse changes in lipid status, whereas initializing feminizing GAHT was associated with metabolically unfavorable changes in body composition.