Early body composition changes in trans women on low-dose estradiol: Comparing oral vs sublingual administration using dual energy absorptiometry and bioelectrical impedance analysis

Background: Low-dose sublingual estradiol gender-Affirming hormone therapy (GAHT) in treatment-naive transgender women effectively suppresses testosterone and initiates breast development, comparable to oral estradiol with cyproterone acetate; however, its impact on body composition remains unstudied. Aim: To assess early body composition changes with low-dose estradiol, compare sublingual versus oral administration efficacy, and evaluate bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) agreement in transgender women undergoing GAHT. Methods: In this 6-month prospective study, 22 treatment-naïve transgender women received either 2 mg/day sublingual estradiol (SLE) or combined oral (CO)-2 mg/day oral estradiol plus 10 mg/day cyproterone acetate. Body composition was assessed using DXA and BIA at baseline and after 6 months. Outcomes: Changes in body composition, including lean body mass, fat mass, visceral fat area, waist-To-hip ratio, and android-To-gynoid fat ratio. Results: BIA and DXA measurements showed good agreement. Both groups experienced decreased lean body mass and increased fat mass. The SLE group showed less increase in total and segmental body fat, and visceral fat area compared to CO. Both treatments decreased waist-To-hip ratio and android-To-gynoid fat ratio, indicating early achievement of a more feminine body shape. Clinical Implications: These findings may help optimize GAHT protocols, improve patient satisfaction with treatment, and enable monitoring outcome assessment in transgender women. Strengths and Limitations: This study provides valuable insights into early body composition changes with low-dose estradiol administration via different administration routes and validates BIA as an alternative to DXA. However, the sample size was relatively small, the study arm allocation was not randomized, and the study duration was only 6 months. Conclusion: Low-dose estradiol induces significant feminizing body composition changes within 6 months of GAHT, with sublingual administration potentially limiting fat accumulation while achieving a feminine body shape. Study registration: ISRCTN15726488 Entire data set found at: https://doi.org/10.17605/OSF.IO/VNC54