Metabolic Features of Assigned Female at Birth Transgender People on Gender-Affirming Hormone Therapy: A Meta-analysis

Purpose: There is a paucity of data on the safety and efficacy of long-term testosterone (T)-based gender-affirming hormone therapy (GAHT) on anthropometric parameters, body composition, and glycolipid metabolism in assigned female at birth (AFAB) persons. The purpose of this study was to provide an updated meta-analysis on this topic.

Methods: We searched PubMed, Scopus, and Cochrane Library for relevant studies. Pre-/post-therapy changes in body mass index (BMI), waist-to-hip ratio (WHR), body composition, lipid glycemic/insulinemic profiles were combined as mean differences (MD) with 95% confidence interval (CI), using random-effect models.

Results: Thirty-nine studies (N=1949) were analyzed. At pooled estimates, GAHT was associated with significant decrease in fat mass (MD: -1.29 kg; 95% CI: -2.52 to -0.05; p=0.04) and increase in lean mass (4.12 kg; 95% CI: 3.07-5.16; p<0.00001), BMI (0.78 kg/m²; 95% CI: 0.50-1.07; p<0.00001), and WHR (0.02; 95%CI: 0.01-0.03; p=0.003) in the absence of heterogeneity (I ²=0%). T therapy was also accompanied by unfavorable effects on lipid profile, including increases in total cholesterol (4.95 mg/dL; 95% CI: 1.53-8.37; p=0.005), LDL (11.15 mg/dL; 95% CI: 7.57-14.74; p<0.00001), and triglycerides (9.49 mg/dL; 95% CI: 4.39-14.58; p=0.0003) and decrease in HDL concentration (-7.52 mg/dL; 95% CI: -9.38 to -5.67; p<0.00001). Finally, T therapy resulted in a significant decrease in blood glucose concentration (-2.06 mg/dL; 95% CI: -3.37 to -0.74; p=0.002), with no significant effects on homeostatic model assessment index of insulin resistance.

Conclusion: T-based GAHT in AFAB people is associated with androgenic changes in body composition and body fat distribution, accompanied by the acquisition of a more unfavorable cardiovascular lipid profile.