Visceral adipose tissue and liver fat on 17-beta estradiol-dominant gender-affirming hormone therapy: A US-based cohort

Abstract Context Data on the metabolic effects of contemporaneous gender-affirming hormone therapy (GAHT) are limited. Objective To characterize the metabolic effects of GAHT, i.e. estradiol with anti-androgen therapy. Design Prospective observational study with a 12-month follow-up period Setting Academic Medical Center in Greater Boston, MA, USA Participants Twenty-six transgender women and non-binary individuals with no history of cardiovascular disease or diabetes who were either planning to initiate or who had recently initiated GAHT consisting of 17 beta(β)-estradiol and anti-androgen therapy. Intervention(s) GAHT Main Outcome Measure(s) The pre-specified primary outcome was the change in visceral adipose tissue (VAT). Pre-specified secondary outcomes included change in bone density, insulin sensitivity, and intrahepatic triglyceride content (hTG). Results Median age of participants was 26 (20, 30) years. After 12 months, VAT mass and volume did not change. While lumbar, total hip and femoral bone density increased, insulin sensitivity did not change. hTG decreased over 12 months (median change: -0.2 -1.3, 0.1%, P=0.03). Total lean body mass and the appendicular lean body mass (ALM)/height2 decreased (mean change: -0.31 ± 0.38kg/m2, P=0.0003). Systemic triglycerides levels increased, whereas HDL-C and LDL-C, did not change over 12 months. Free testosterone levels at follow-up independently predicted the change in hTG, controlling for estradiol levels, body mass index, and waist-to-hip ratio at follow-up. Conclusions Key indices of metabolic health, such as VAT and insulin sensitivity, did not change after 12 months of GAHT. ALM/height2, a predictor of sarcopenia, unfavorably decreased, while hTG favorably decreased. Awareness of the metabolic effects of GAHT may lead to the implementation of strategies aimed at mitigating sarcopenia risk. NCT registration NCT04128488