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Cyproterone Acetate Or Spironolactone in Lowering Testosterone Concentrations for Transgender Individuals Receiving Oestradiol Therapy

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Cyproterone Acetate Or Spironolactone in Lowering Testosterone Concentrations for Transgender Individuals Receiving Oestradiol Therapy ID: 19-0272 8 7 L Angus et al. Anti-androgens in 8:7 935–940 transfeminine individuals RESEARCH Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy Lachlan Angus1, Shalem Leemaqz2, Olivia Ooi1, Pauline Cundill3, Nicholas Silberstein3, Peter Locke3, Jeffrey D Zajac1 and Ada S Cheung1 1Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia 2Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia 3Equinox Gender Diverse Clinic, Thorne Harbour Health, Fitzroy, Victoria, Australia Correspondence should be addressed to A S Cheung: [email protected] Abstract Background: Oestradiol with or without an anti-androgen (cyproterone acetate or Key Words spironolactone) is commonly prescribed in transfeminine individuals who have not had f transgender persons orchidectomy; however, there is no evidence to guide optimal treatment choice. f transsexualism Objective: We aimed to compare add-on cyproterone acetate versus spironolactone in f gender identity lowering endogenous testosterone concentrations in transfeminine individuals. f gender dysphoria Design: Retrospective cross-sectional study. f androgens 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. Endocrine Connections Further prospective studies are required. (2019) 8, 935–940 https://ec.bioscientifica.com © 2019 The authors This work is licensed under a Creative Commons https://doi.org/10.1530/EC-19-0272 Published by Bioscientifica Ltd Attribution-NonCommercial-NoDerivatives 4.0 InternationalDownloaded License. from Bioscientifica.com at 09/24/2021 02:30:42PM via free access -19-0272 PB–6 L Angus et al. Anti-androgens in 8:7 936 transfeminine individuals Introduction electrolyte imbalance and hypotension, which impact upon treatment choice. Rapid rises in demand for transgender health services In this retrospective audit of individuals on established have been observed worldwide (1, 2). Birth-assigned feminising hormone therapy, we aimed to compare the males who wish to transition to female (hereafter termed serum total testosterone concentrations of individuals on transfeminine individuals) are typically treated with established treatment with oestradiol alone, oestradiol oestradiol as feminising gender-affirming hormone with additional cyproterone acetate and oestradiol with therapy (3). Goals of therapy are generally to increase additional spironolactone. We hypothesised that in serum oestradiol concentrations and lower serum total transfeminine individuals on oestradiol therapy, a greater testosterone concentrations to achieve sex steroid proportion of individuals receiving additional cyproterone concentrations in the female reference range. Over acetate would have total testosterone concentrations 3–24 months, this leads to feminine physical characteristics <2 nmol/L (the female reference range in our laboratory) including softening of skin, a decrease in facial and body compared to those receiving additional spironolactone or hair growth, changes in body fat and muscle distribution, oestradiol alone. as well as breast development (4). Oestradiol improves psychological functioning in transfeminine individuals (5); however, oestradiol alone is usually insufficient to Methods lower serum total testosterone concentrations from a male to a female reference range. Oestradiol suppresses A retrospective audit of de-identified electronic medical gonadotropin-releasing hormone (GnRH) via negative records was performed of new consultations for gender feedback, in turn partially lowering testosterone. However, dysphoria across two gender clinics in Melbourne, as the majority of individuals (82% in our clinics (1)) do Australia: (a) Equinox Gender Diverse Clinic, an adult not undergo genital reassignment surgery to remove the primary care general practice clinic with a focus on testes, which are responsible for >95% of testosterone transgender health and (b) an adult endocrine specialist production, most individuals will require treatment with clinic. New consecutive consultations between 1 January an additional anti-androgen drug. Anti-androgens such 2011 and 31 December 2016 were analysed. As the as cyproterone acetate or spironolactone are commonly primary care clinic commenced on 22 February 2016, added to oestradiol, lowering or blocking the effects of data were analysed for the first 12 months of operation testosterone to aid development of feminising physical until 22 February 2017. The study was approved by characteristics. the Austin Health Human Research Ethics Committee In transfeminine individuals wishing to inhibit (LNR/17/Austin/102) and the nature of the study did not androgenic physical characteristics, choice of anti- necessitate informed consent. androgen agent is a common clinical scenario faced by Clinical characteristics of the audit have been patients and treating clinicians alike. Whilst both anti- previously published (1). This cross-sectional analysis androgen agents, cyproterone acetate and spironolactone, included transfeminine individuals newly presenting have been shown to lower serum testosterone to the clinics who had been on established feminising concentrations if added to oestradiol treatment, there hormone therapy with oestradiol for at least 6 months is little evidence to guide the superiority of one anti- and had fasting serum sex steroid results available androgen over another (6). Both cyproterone acetate and within 1 month of their initial consultation. We spironolactone have peripheral anti-androgen effects, excluded individuals who were expected to have castrate but cyproterone acetate additionally has progestogenic testosterone concentrations (previous orchidectomy or actions which may be more effective in suppressing GnRH concurrent GnRH agonist therapy) and individuals on and in turn, testosterone concentrations. ethinyl oestradiol treatment as this was not measurable As there are no data to support one drug over the on oestradiol immunoassay. other, prescription of anti-androgens is often a random The primary outcome of interest was serum fasting choice with over 90% of experienced prescribers of gender- total testosterone concentration by treatment group: (a) affirming hormone therapy using both agents with no oestradiol alone, (b) oestradiol plus additional cyproterone rationale for one or the other (7). Yet, cyproterone may acetate and (c) oestradiol plus additional spironolactone. be associated with adverse effects such as depression, and Other parameters of interest included serum oestradiol spironolactone may be associated with excess diuresis, concentration, potassium, urea and creatinine, https://ec.bioscientifica.com © 2019 The authors This work is licensed under a Creative Commons https://doi.org/10.1530/EC-19-0272 Published by Bioscientifica Ltd Attribution-NonCommercial-NoDerivatives 4.0 InternationalDownloaded License. from Bioscientifica.com at 09/24/2021 02:30:42PM via free access L Angus et al. Anti-androgens in 8:7 937 transfeminine individuals haemoglobin, liver function (alanine transaminase (ALT)), Pharmaceutical Benefits Scheme. The median doses used oestradiol valerate dose and blood pressure. were oestradiol valerate 6 mg (4, 6), cyproterone acetate As data were obtained retrospectively, sex steroid 50 mg (25, 50) and spironolactone 100 mg (87.5–200). concentrations, biochemistry and haemoglobin were The serum total testosterone concentrations for the performed using immunoassay available as standard three groups are shown in Fig. 1. The median serum care for clinical decision-making. Multiple National total testosterone concentrations were 10.5 nmol/L Association of Testing Authorities (NATA, the national (4.9–17.2) in the oestradiol alone group, 0.8 nmol/L accreditation body for Australia) accredited laboratories (0.6–1.2) in the cyproterone group and 2.0 nmol/L available locally were used. (0.9–9.4) in the spironolactone group. On univariate Statistical analyses were performed using R (v3.5.1; analysis, the cyproterone group had significantly R foundation
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