Background: Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to the effects of GAHT on body composition, fat distribution, and insulin resistance.
Aim: To evaluate the impact of GAHT on body fat distribution and insulin resistance in transgender individuals.
Methods: This cross-sectional study compared 84 transgender individuals (41 ‘male-to-female’ trans women and 43 ‘female-to-male’ trans men) on established GAHT (>12 months) with 85 age-matched cisgender controls (37 men and 48 women, respectively). Body composition was measured using dual-energy x-ray absorptiometry and insulin resistance was estimated from the updated Homeostasis Model of Insulin Resistance (HOMA2-IR). Multiple linear regressions were used to examine relationships between HOMA2IR and fat mass with gender, adjusting for age and total duration of GAHT. Mean difference (95% confidence intervals) is presented. Pearson correlation was used to analyse correlations of HOMA2-IR with fat mass.
Results: Mean age was 30.3 years in trans men and 40.8 years in trans women. Compared to control women, trans men had mean difference of +7.8kg (95%CI 4.0, 11.5) (p<0.001) in lean mass and higher android:gynoid fat ratio (0.2 (0.1, 0.3), p<0.001), but no difference in overall fat mass or insulin resistance. Compared to control men, trans women had mean difference in lean mass of -6.8kg (95%CI -10.6, -3.1) (p<0.001), fat mass of +9.2kg (95%CI 3.9, 14.5) (p=0.001), lower android:gynoid ratio -0.1 (-0.2,-0.0), p<0.05), and higher insulin resistance (+60% (33 – 92), p<0.001). Higher HOMA2-IR correlated with higher android (r2= 0.712, p<0.001) and gynoid (r2= 0.572, p<0.001) fat mass.
Conclusion: Feminising hormone therapy is associated with insulin resistance related to higher fat mass compared to cisgender male controls. This may predispose to increased cardiovascular risk in trans women. Despite fat redistribution, no adverse changes in insulin resistance were observed in trans men.