IS THERE A DOSE OF CYPROTERONE ACETATE LOW ENOUGH TO AVOID HYPERTENSION DEVELOPMENT IN YOUNG TRANSGENDER WOMEN?

Abstract

Objective: Cyproterone acetate (CPA) is a progestagen receptor agonist and androgen receptor antagonist widely used in gender-affirming hormonal therapy (GAHT) for transgender women. It is devoid of the mineralocorticoid blocking effect of native progesterone, thus its combination with oestradiol may elicit hydrosaline retention and hypertension. In a retrospective analysis we have found that using CPA for 5 years in young transgender women increases very significantly their SBP and their incidence of hypertension. Due to risks such as meningioma and liver toxicity, the European Medicines Agency (EMA) recommends avoiding doses >10 mg/day if possible; however, present guidelines for GAHT recommend doses up to 100 mg/day. While lower doses may be effective and safer, the dose-dependence for hypertension development with CPA has not been studied. We undertook to study the association between the cumulative dose of CPA in young transgender women and their incidence of hypertension. Design and method: Retrospective review of the clinical records of female transgender people <30-years-old treated with oestradiol + CPA for 5 years. All subjects gave informed consent. They were stratified by quartiles of cumulative CPA intake. We were unable to use doses < 25 mg/day, as only 50 mg pills are available. Results: Data were obtained from 56 subjects. The global adjusted annualized incidence of hypertension 4.96% vs. 0.98% in the reference population (transgender women treated with oestradiol without antiandrogen). By quartiles the incidences were 2.52%/4.13%/5.76%/7.31%, p <0.001 (Figure 1A). Their global adjusted SBP increase was 14 vs. 3 mmHg; by quartiles 7/11/16/22 mmHg, p <0.001 (Figure 1B). Conclusions: We found a clear dose-dependence for the incidence of hypertension associated with CPA in young transgender women, but even the lowest doses we were able to manage did significantly increase the risk. We cannot however rule out that doses as low as 10 mg/day may be effective and safer. We believe that the present recommendations of high CPA doses for GAHT should be reconsidered.