SAT421 Near Term Cardiometabolic Outcomes of Testosterone Therapy In Transgender Boys And Men

Abstract

Abstract Disclosure: J. Dey: None. C. O’neill: None. C. Bingham-Tyson: None. M.E. Widlansky: None. S. Cabrera: None. Background: Medical therapy for transgender males may include GnRH agonists and gender affirming testosterone (T) hormone therapy (GAHT). Given the clear sexual dimorphism in cardiometabolic disease risk, it is reasonable to assume GAHT affects the cardiometabolic health of transmales. In cisgender women, hypoestrogenism reduces vasculo-protective E2-mediated estrogen receptor alpha (ERα) expression and increases susceptibility to future vascular complications. Whether similar changes occur in transmales on GAHT remains poorly studied. To our knowledge, no study has addressed possible mechanisms by which GAHT affects vascular physiology in transmales. Here, we present study procedures and preliminary results of an ongoing 2-site trial that aims to examine the impact of GAHT on cardiometabolic health in transmales. The primary outcome is the change in brachial artery flow-mediated dilation (FMD%), an in vivo measure of human vascular endothelial health, after 1-yr of GAHT. We hypothesize that, in transmales with completed E2-driven puberty, GAHT will induce a regression of vascular endothelial function towards that of cismales by suppressing circulating E2 and vascular ERα and that lesser regression will be seen in transmales initiating GAHT before completion of full E2-mediated pubertal progression. Methods: This is a longitudinal observational study of transmales aged 12-30 yrs over the first year of GAHT, with visits at baseline (BL), 6-mo, and 1-yr, matched by age and puberty to healthy cisfemales and cismales with endogenous sex hormone production. To detect a significant relative change in FMD% at 1-yr from BL, 80 participants are needed to enroll (40 transmales, 20 cisfemales, 20 cismales) and 64 to complete all visits. Vascular function is assessed by FMD% and circulating markers of endothelial activation. Metabolism/inflammation is assessed by fasting lipids, glucose, insulin, leptin, and serum cytokines. Body composition is assessed by DXA. Results: To date, 34 participants (20 transmales, 5 cisfemales, and 9 cismales) have had BL visits and 13 have completed 6-mo visits. At BL, trans and cis participants are matched for age and puberty and have similar vascular function, body composition, and metabolism. While the small number of participants with BL and 6-mo data precludes statistical analyses, initial findings have not identified significant changes in vascular function, metabolism, or body composition in transmales on GAHT. The study is ongoing. Conclusion:This study will be completed in 2024 and should inform novel mechanisms by which GAHT affects vascular function and cardiometabolic health relative to cisgender controls. Completion of the cohort will allow for proper analyses, powered to detect a change in FMD% after 1-yr of GAHT. On-going work includes retention of a well-matched, but pubertal stage diverse, cohort. Presentation: Saturday, June 17, 2023