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Published on: January 10, 2025
Effect of anti-androgens on body composition in transgender people: Secondary analysis of a randomized clinical trial
Lachlan M Angus1,2, Shalem Y Leemaqz3, James C G Doery4,5
1Department of Medicine, The University of Melbourne, Victoria, Australia.
Background:
Transgender people desiring feminization commonly use cyproterone acetate or spironolactone, but the optimal anti-androgen to achieve feminization of body composition is unclear.
Aims:
To assess the effect of anti-androgens on body composition. We hypothesized cyproterone acetate would result in a greater increase in body fat than spironolactone due to greater suppression of serum testosterone concentration and more potent androgen receptor antagonism.
Methods:
Secondary analysis of a randomized clinical trial of transgender people aged 18+ years newly commencing estradiol and randomized to spironolactone 100 mg daily or cyproterone acetate 12.5 mg daily for six months. Pre-specified secondary outcomes including waist circumference, hip circumference, waist/hip ratio and whole body dual x-ray absorptiometry (DXA).
Results:
Sixty-three people were included in intention-to-treat analysis (cyproterone acetate n = 32, spironolactone n = 31). Overall, hip circumference increased but there was no change in waist circumference or waist/hip ratio. On whole body DXA, total body fat, percentage body fat, gynoid fat and android fat increased and trunk/limb fat ratio, android/gynoid fat ratio, total lean mass and appendicular lean mass decreased. No changes in visceral adipose tissue. Cyproterone acetate was associated with a greater increase in percentage total body fat (+1.98%, 0.34 to 3.63, p = 0.02), gynoid fat (+2.51%, 0.69 to 4.34, p = <0.01) and android fat (+2.63%, 0.40 to 4.85, p = 0.02) than spironolactone. Serum estradiol concentration was higher in the cyproterone acetate group (mean difference +228.38 pmol/L, 62.54 to 394.31, p < 0.01) but adjusted modeling remained statistically significant.
Discussion:
Feminization of body composition was evident following six months of hormone therapy. Cyproterone acetate caused a greater increase in percentage total body fat, gynoid fat and android fat compared to spironolactone. Given the change in the android/gynoid fat ratio was similar, and that the waist/hip ratio did not change over time, it is unclear whether cyproterone acetate offers an advantage to spironolactone.
