Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents

Abstract

Background: Cyproterone acetate (CA) is an antiandrogenic progestin commonly used in adult transwomen to suppress endogenous androgens, often in combination with estrogens to induce feminization.

Aim: To assess the (side) effects and biochemical changes of CA alone and in combination with estrogens in adolescent trans-girls.

Methods: This study was a retrospective analysis of clinical and biochemical data from 27 trans-girls who presented at Tanner stage G4 and were treated with CA monotherapy for at least 6 months (mean = 12 months) and then in combination with incremental doses of estrogens (CA + E; mean = 16 months). Statistical analysis of data included paired or unpaired Student t-test or Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate.

Outcomes: Anthropometrics, reported beneficial and side effects, safety parameters, and hormone levels.

Results: Physical changes included decrease of facial and non-facial hair growth. One third showed breast development under CA (Tanner stages B2-B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5% respectively, during CA + E. Reported side effects during CA and CA + E were breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes were observed. Main safety parameters showed the following changes. Hemoglobin and hematocrit decreased and liver enzymes transiently and modestly increased during CA. Triglycerides and cholesterol levels slightly decreased during CA but returned to baseline during CA + E; glucose metabolism was unaffected. Relevant hormonal changes included a decrease in gonadotropins during CA + E and in total and free testosterone levels throughout treatment. Prolactin levels increased during CA and were restored during CA + E.

Clinical implications: CA produced modest feminizing effects in trans-girls and therefore might be a valuable alternative in situations in which gonadotropin-releasing hormone analogues are not the treatment of choice and/or are not reimbursed.

Strengths and limitations: This is the first study to report on the effects of CA in the treatment of trans-girls and one of the few to report on the use of estrogens in this population. Limitations are the modest sample size and the retrospective nature of this study.

Conclusion: Treatment with CA in late-pubertal trans-girls overall was safe and well tolerated and induced mild clinical and biochemical feminizing changes. Rapid further feminization was observed with incremental doses of E. Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747-757.

Keywords: Anthropometry; Biochemical Changes; Cross-Sex Hormones; Cyproterone Acetate; Progestins; Transgender Youth.