Body Composition and Markers of Cardiometabolic Health in Transgender Youth on Gonadotropin-Releasing Hormone Agonists

Purpose: Up to 1.8% of youth identify as transgender; many will be treated with a gonadotropin-releasing hormone agonist (GnRHa). The impact of GnRHa on insulin sensitivity and body composition in transgender youth is understudied. We aimed to evaluate differences in insulin sensitivity and body composition in transgender youth on GnRHa therapy compared with cisgender youth. Methods: Transgender participants were matched to cisgender participants on age, body mass index, and sex assigned at birth. Transgender males (n=9, ages 10.1-16.0 years) on GnRHa (mean +/- standard deviation duration of exposure: 20.9 +/- 19.8 months) were compared with cisgender females (n=14, ages 10.6-16.2). Transgender females (n=8, ages 12.6-16.1) on GnRHa (11.3 +/- 7 months) were compared with cisgender males (n=17, ages 12.5-15.5). Differences in insulin sensitivity (1/[fasting insulin], homeostatic model of insulin resistance [HOMA-IR]), glycemia (hemoglobin A1C [HbA1c], fasting glucose), and body composition (dual-energy X-ray absorptiometry) were evaluated using a mixed linear regression model. Results: Transgender males had lower 1/fasting insulin and higher HOMA-IR (p=0.031, p=0.01, respectively), fasting glucose (89 +/- 4 vs. 79 +/- 13 mg/dL, p=0.012), HbA1c (5.4 +/- 0.2 vs. 5.2 +/- 0.2%, p=0.039), and percent body fat (36 +/- 7 vs. 32 +/- 5%, p=0.042) than matched cisgender females. Transgender females had lower 1/fasting insulin and higher HOMA-IR (p=0.028, p=0.035), HbA1c (5.4 +/- 0.1% vs. 5.1 +/- 0.2%, p=0.007), percent body fat (31 +/- 9 vs. 24 +/- 10%, p=0.002), and lower percent lean mass (66 +/- 8 vs. 74 +/- 10%, p<0.001) than matched cisgender males. Conclusion: Transgender youth on a GnRHa have lower estimated insulin sensitivity and higher glycemic markers and body fat than cisgender controls with similar characteristics. Longitudinal studies are needed to understand the significance of these changes. Clinical Trial.gov ID: NCT02550431.