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

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.

To evaluate prospective changes in CMD risk markers during GAHT.

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.

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.

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.