7143 Near Term Cardiometabolic Outcomes in Transgender Boys and Men in the First Year of Gender-Affirming Testosterone Therapy

Abstract Disclosure: J. Dey: None. M. Widlansky: None. S. Cabrera: None. Background: Gender affirming testosterone (T) therapy is used to masculinize transgender adolescent men (TMs), resulting in elevated T and suppressed estradiol (E2). In cis-females, hypoestrogenism reduces vaso-protective E2-mediated estrogen receptor expression, decreasing nitric oxide vasodilation and increasing susceptibility to future vascular complications. Whether T promotes similar changes in TMs remains poorly understood. Methods: A longitudinal observational study is conducted in TMs aged 12-30yrs over the 1st yr of T, with visits at baseline (BL; pre-T), 6mo, and 1yr, compared to cis-males (CMs) with endogenous T. Primary outcome is change in brachial artery flow-mediated dilation (FMD%), an in vivo measure of vascular endothelial health, after 1yr of T. To detect a significant relative change in FMD%, 60 participants are needed (40 TMs, 20 CMs). Metabolic profile is assessed by fasting lipids, glucose, and insulin. Body composition is assessed by BMI and DEXA. Differences in mean values between and within a cohort were analyzed using the unpaired two-tailed T-test assuming unequal and equal variances, respectively. Results: To date, 51 participants are enrolled; the 21 participants who fully completed the study are included here (13 TMs, 8 CMs). At BL, TMs were post-menarchal with a mean age of 15.6yrs, ht 162.6cm, and BMI z-score 0.47. At BL, 46% were on progestin-only menstrual suppression. CMs had a mean age of 18.4yrs, ht 170.7cm, and BMI z-score 0.13. Cohorts were similar for age, height, and BMI.At BL, FMD% was higher in TMs than CMs (8.2 vs 4.6, p=0.01) but not at 1yr (6.9 vs 6.2, p=0.6). FMD% did not change in TMs receiving T over 1yr (8.2 vs 6.9, p=0.3). At BL, the brachial artery resting diameter (mm) was lower in TMs than CMs (2.6 vs 3.5, p<0.01) and remained such at 1-yr. Resting diameter increased in TMs over 1yr of T (2.6 vs 3.1, p<0.01) but not in CMs. There were no differences in resting or hyperemic flow velocity, or FMD (mm) between or within groups. At BL, % lean body mass (%LBM) was lower in TMs than CMs (60 vs 72, p<0.01) and estimated percent visceral adiposity tissue (%VAT) was higher (26 vs 14, p<0.01). In TMs, %LBM increased (60 vs 66, p <0.01) and %VAT decreased (26 vs 21, p<0.01) over 1yr of T, such that TMs and CMs were similar at 1yr. At BL, TMs had lower T but similar E2 (46 vs 27 pg/mL, p=0.2) to CMs. At 1-yr, TMs and CMs had similar T (556 vs 574 ng/dL, p=0.9) and E2 (52 vs 29, p=0.1). In TMs, T did not change E2. Lipid and glycemic indices did not change over 1yr in TMs. Conclusion: Initial analyses suggest that T does not affect FMD; however, FMD% interpretation is confounded by the small number of participants, progestins at BL in TMs, and the lower resting brachial artery diameter in TMs. The stable E2 in TMs on T may explain the stable FMD%. Overall, our findings suggest T results in relative stability of vascular and metabolic function and a beneficial shift in body composition in TMs. Presentation: 6/2/2024