Effects of gender-affirming hormone therapy on cardiovascular risk factors focusing on glucose metabolism in an Austrian transgender cohort.

Objective: We aimed to investigate the effect of gender-affirming hormone therapy (GAHT) on cardiovascular disease risk factors focusing on glucose tolerance. Patients and Methods: This primarily translational study enrolled 16 transgender persons assigned female at birth (AFAB), 22 assigned male at birth (AMAB), and 33 age- and BMI-matched cisgender controls at the Medical University of Vienna from 2013 to 2020. A 3-Tesla MRI scan to measure intramyocardial, pancreatic, hepatic fat content and subcutaneous-to-visceral adipose tissue ratio (SAT/VAT-ratio), an oral glucose tolerance test (oGTT), bloodwork including brain natriuretic peptide (pro-BNP), sex hormones and two glucose-metabolism related biomarkers (adiponectin, betatrophin) were performed. Results: Estrogen intake was associated with higher fasting insulin (p = 0.034) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p = 0.037), however, lower HbA1c levels (p = 0.031) in AMAB than cisgender males. Adiponectin (p = 0.001) and betatrophin (p = 0.034) levels were higher in AMAB than cisgender males, but similar to cisgender females. Compared to cisgender females, AFAB displayed no differences in glucose metabolism or SAT/VAT-ratio. AFAB had lower pro-BNP levels (p = 0.014), higher liver enzymes (AST: p = 0.011; ALT: p = 0.012) and lower HDL levels (p = 0.017) than cisgender females, but comparable levels to cisgender males. AMAB showed an increased heart rate (p < 0.001) and pro-BNP (p = 0.002) levels, but a more favorable SAT/VAT-ratio (p = 0.013) and lower creatine kinase (CK) (p = 0.001) than cisgender males. There were no relevant differences in organ fat content between transgender persons and their respective cisgender controls. Conclusion: In AMAB, most investigated parameters adapted to levels seen in cisgender females except for parameters related to fasted insulin resistance. AMAB should be monitored with respect to the development of insulin resistance.