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

Abstract

Background Oestradiol with or without an anti-androgen (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. Objective We aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals. Design Retrospective cross-sectional study. Methods We analysed 114 transfeminine individuals who had been on oestradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; oestradiol alone (n = 21), oestradiol plus cyproterone acetate (n = 21) and oestradiol plus spironolactone (n = 38). Secondary outcomes included serum oestradiol concentration, oestradiol valerate dose, blood pressure, serum potassium, urea and creatinine. Results 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 (0.8 nmol/L (0.6–1.20)) compared with the spironolactone group (2.0 nmol/L (0.9–9.4), P = 0.037) and oestradiol alone group (10.5 nmol/L (4.9–17.2), P < 0.001), which remained significant (P = 0.005) after adjustments for oestradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily oestradiol dose, blood pressure, serum oestradiol, potassium or creatinine. Conclusions 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.

Transgender adults, gender-affirming hormone therapy and blood pressure: a systematic review

“…No records were identified through other resources. Following the screening of these records' titles and abstracts, 84 full text articles were assessed for eligibility; however, 70 articles were excluded due to not being original investigations, not assessing relevant outcomes, not obtaining pre-GHT outcome measurements [14] or including adolescent populations [15][16][17][18].…”

Relationships between body mass index with oral estradiol dose and serum estradiol concentration in transgender adults undergoing feminising hormone therapy

“…No studies have examined the optimal estradiol concentrations in transfeminine individuals. Based on cross-sectional data, 12 Australian consensus guidelines recommend targeting trough estradiol concentrations of 250-600 pmol/l, 5 whereas the Endocrine Society Clinical Practice Guidelines recommend a target range of 367-734 pmol/l based on the physiological range of pre-menopausal women. 1 The estradiol assay used and timing of blood testing in relation to the estradiol dose are other important considerations when interpreting the estradiol concentration.…”

Principles of management of women with hirsutism – a dermatologist’s perspective

“…Another antiandrogen used in the treatment of hirsutism is cyproterone acetate, which is most commonly prescribed in Poland as one of the components of a combined oral contraceptive pill. Cyproterone acetate is a progestin with antiandrogenic activity resulting from the reduction of 5α-reductase activity and androgen receptor inhibition [47]. In the literature, a combined contraceptive pill consisting of 2 mg of cyproterone acetate and 35 μg of ethyl estradiol is described as effective in the treatment of light and moderate hirsutism.…”

“…Kolejnym antyandrogenem stosowanym w leczeniu hirsutyzmu jest octan cyproteronu, który w Polsce jest najczęściej przepisywany jako jeden ze składników doustnej dwuskładnikowej tabletki antykoncepcyjnej. Octan cyproteronu jest progestyną o działaniu antyandrogennym wynikającym ze zmniejszenia aktywności 5α-reduktazy i hamowania receptorów androgenowych [47]. Doniesienia literaturowe wskazują na skuteczność dwuskładnikowych doustnych środków antykoncepcyjnych zawierających 2 mg octanu cyproteronu i 35 μg etyloestradiolu w leczeniu lekkiego i umiarkowanego hirsutyzmu.…”