PMON280 Effect of Gender Affirming Hormone Therapy (GAHT) on Adipose Tissue Morphology and Metabolism in Transgender Individuals

BACKGROUND: Circulating sex hormones exert unique effects on metabolism, leading to sexual dimorphism in white adipose tissue distribution and function. The gender affirming hormone therapy (GAHT) or cross-sex hormone therapy (CSHT) for transgender patients lower the endogenous sex hormones while raising the opposite sex hormones. Sex hormones are known to have a significant impact on white adipose tissue and metabolism. However, long-term metabolic changes with GAHT in transgender individuals have not been studied, nor are the underlying mechanisms properly elucidated. HYPOTHESIS: We test the hypothesis that GAHT will result in sexual dimorphic changes in morphology and function of white adipose tissue according to the type of sex hormones used and the native sex of the patients. AIM 1: To study the effect of cross-sex hormones on clinical parameters such as blood pressure, weight, waist-hip circumference ratio, serum lipids, insulin sensitivity AIM 2: To study the changes in human subcutaneous white adipose tissue (SWAT) distribution and expansion with GAHT AIM 3: To study changes in circulating metabolites and adipokines, and pro-inflammatory and pro-fibrotic gene expression in SWAT with GAHT. METHODOLOGY: 31 hormone-naive patients (19 Male-to-Female; MtF and 12 Female-to-Male; FtM) were enrolled in the longitudinal study and followed up for 3 years. Clinical parameters and blood samples were gathered at baseline and at 6 month intervals. DXA scans and fat biopsies (peri-umbilical SWAT) were performed at baseline and at 1 year intervals. RESULTS: The results presented here compare baseline and at 1 year of GAHT. There was an increase in total cholesterol in the MtF group. HOMA-IR, total fat mass and visceral fat mass increased in MtF group, while they decreased in the FtM group. In MtF group, lean mass and bone mineral content (BMC) decreased at 1 year, but no change was observed in the FtM group. On histological assessment, fat cell size increased in MtF group, while it decreased in the FtM group. CONCLUSION: In MtF transgender patients, androgen deprivation and estrogen treatment resulted in reduced insulin sensitivity together with a rise in total cholesterol possibly via a decrease in lean mass and adipose tissue expansion through significant adipocyte hypertrophy. In FtM transgender patients, testosterone treatment caused improved insulin sensitivity possibly via a decrease in total and visceral fat mass. The greatest strengths of our project include its longitudinal nature over 3 years to capture long-term effects in the same patients as well as deeper mechanistic insights into the underlying metabolite, adipokine and gene expression changes. The limitations of our study include the small sample size with heterogeneity of study population in terms of demographics and lifestyles. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.