Objective: Transgender women commonly use cyproterone or spironolactone as anti-androgens with estradiol to assist with feminisation. However, the optimal anti-androgen is unclear. We aimed to assess the effect of these anti-androgens on breast development and hypothesised that cyproterone would result in greater breast development than spironolactone due to greater androgen receptor antagonism and suppression of serum total testosterone.
Design: Double-blind, randomised controlled trial
Methods: Transgender women newly commencing estradiol were randomised to spironolactone 100mg daily or cyproterone 12.5mg daily for six months. The primary outcome was measurement of breast development via breast chest distance with secondary outcomes of estimated breast volume using the BreastIdea Volume Estimator application and serum total testosterone.
Results: Fifty-five participants were included in per protocol analysis (cyproterone group n=28, spironolactone group n=27). Baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable. At six months, the mean (standard deviation) breast chest distance was 9.2cm (3.0) in the cyproterone group versus 8.3cm (2.7) in the spironolactone group (p=0.27). The mean (SD) estimated breast volume was 190.25 mL (158.60) in the cyproterone group and 157.84mL (112.03) in the spironolactone group (p=0.39) with significant inter-individual variation (range 20.27 – 787.77 mL). The mean (SD) serum total testosterone was 1.48 nmol/L (3.45) in the cyproterone group and 4.29 nmol/L (5.44) in the spironolactone group (p=0.04). Serum estradiol levels were comparable. Use of cyproterone was associated with mild hyperprolactinaemia and spironolactone with an increase in serum urea and creatinine.
Conclusions: Choice of anti-androgen should be individualised based on clinician and patient preference, with consideration of associated side effects. Further research is needed to optimise breast development in transgender women.