Effect of anti-androgens on body composition in transgender people: secondary analysis of a randomized clinical trial
Date
2025
Authors
Angus, L.M.
Leemaqz, S.Y.
Doery, J.C.G.
Cheung, A.S.
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Journal article
Citation
International Journal of Transgender Health, 2025; 1-12
Statement of Responsibility
Lachlan M. Angus, Shalem Y. Leemaqz, James C.G. Doery, Ada S. Cheung
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Abstract
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.
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OnlinePubl.
Available online 12 July 2025.
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© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.