Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving estradiol therapy.

Abstract

Estradiol with or without an antiandrogen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy, however there is no evidence to guide optimal treatment choice. We aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals. Retrospective cross-sectional study. We analysed 114 transfeminine individuals who had been on estradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; estradiol alone (n=21), estradiol plus cyproterone acetate (n=21) and estradiol plus spironolactone (n=38). Secondary outcomes included serum estradiol concentration, estradiol valerate dose, blood pressure, serum potassium, urea and creatinine. Median age was 27.0 years (22.5, 45.1) and median duration of hormone therapy was 1.5 years (0.9, 2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8nmol/L (0.6, 1.20)) compared with the spironolactone group (2.0nmol/L (0.9, 9.4), p=0.037) and estradiol alone group (10.5nmol/L (4.9, 17.2), p<0.001), which remained significant (p=0.005) after adjustments for estradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily estradiol dose, blood pressure, serum estradiol, potassium or creatinine. The cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.