Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Effect of spironolactone and cyproterone acetate on body composition in transgender people: secondary analysis of a randomised clinical trial (#90)

Lachlan M Angus 1 2 , Shalem Y Leemaqz 3 , James CG Doery 4 5 , Ada S Cheung 1 2
  1. Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia
  2. Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia
  3. College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
  4. Chemical Pathology, Monash Health, Clayton, VIC, Australia
  5. Department of Medicine, Monash University, Clayton, VIC, Australia

Aims: Feminising hormone therapy in transgender people causes gynoid body fat redistribution.  Cyproterone acetate and spironolactone are commonly used with estradiol, but the optimal anti-androgen is unknown. 

Methods: In a randomised clinical trial, transgender people commencing estradiol were randomised to spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six month.  As a pre-specified secondary outcome, body composition was measured including waist circumference, hip circumference and waist hip ratio at 0, 3 and 6 months, and whole body dual x-ray absorptiometry (DXA) at 0 and 6 months.

Results: Sixty-three people were included in intention-to-treat analysis (cyproterone acetate n=32, spironolactone n=31).  At six months, there was no difference in waist circumference (mean difference -1.21cm, 95% CI -7.84 to 5.24, p=0.7), hip circumference (1.36cm, -0.69 to 3.42, p=0.2) or waist hip ratio (-0.03, -0.10 to 0.04, p=0.4).  Whole body DXA showed greater total percentage body fat (+1.98%, 0.34 to 3.63, p=0.02), percentage gynoid fat (+2.51%, 0.69 to 4.34, p=0.008) and lower percentage android fat (-2.63%, 0.40 to 4.85, p=0.02) in the cyproterone acetate group.  There was no difference in estimated visceral adipose tissue mass (6.28g, -11.87 to 24.42, p=0.5). Serum estradiol concentration was unexpectedly higher in the cyproterone acetate group over six months (+228.38 pmol/L, 62.45 to 394.31, p=0.007) but further modelling adjusting for serum estradiol concentration showed that these comparisons remained statistically significant.  There was no between-group difference in serum total testosterone concentration (-3.33 nmol/L, -6.99 to 0.32, p=0.07).

Conclusion: Cyproterone acetate resulted in a greater increase in total percentage body fat and gynoid fat and lower android fat compared to spironolactone over six months.  There was no difference in estimated visceral adipose tissue mass, waist circumference, hip circumference or waist hip ratio.  Further research is needed to optimise feminisation in transgender people.