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.

BackgroundPrior to the start of cross-sex hormone therapy (CSH), androgenic progestins are often used to induce amenorrhea in female to male (FtM) pubertal adolescents with gender dysphoria (GD). The aim of this single-center study is to report changes in anthropometry, side effects, safety parameters, and hormone levels in a relatively large cohort of FtM adolescents with a diagnosis of GD at Tanner stage B4 or further, who were treated with lynestrenol (Orgametril®) monotherapy and in combination with testosterone esters (Sustanon®).MethodsA retrospective analysis of clinical and biochemical data obtained during at least 6 months of hormonal treatment in FtM adolescents followed at our adolescent gender clinic since 2010 (n = 45) was conducted. McNemar’s test to analyze reported side effects over time was performed. A paired Student’s t test or a Wilcoxon signed-ranks test was performed, as appropriate, on anthropometric and biochemical data. For biochemical analyses, all statistical tests were done in comparison with baseline parameters. Patients who were using oral contraceptives (OC) at intake were excluded if a Mann-Whitney U test indicated influence of OC.ResultsMetrorrhagia and acne were most pronounced during the first months of monotherapy and combination therapy respectively and decreased thereafter. Headaches, hot flushes, and fatigue were the most reported side effects. Over the course of treatment, an increase in musculature, hemoglobin, hematocrit, creatinine, and liver enzymes was seen, progressively sliding into male reference ranges. Lipid metabolism shifted to an unfavorable high-density lipoprotein (HDL)/low-density lipoprotein (LDL) ratio; glucose metabolism was not affected. Sex hormone-binding globulin (SHBG), total testosterone, and estradiol levels decreased, and free testosterone slightly increased during monotherapy; total and free testosterone increased significantly during combination therapy. Gonadotropins were only fully suppressed during combination therapy. Anti-Müllerian hormone (AMH) remained stable throughout the treatment. Changes occurred in the first 6 months of treatment and remained mostly stable thereafter.ConclusionsTreatment of FtM gender dysphoric adolescents with lynestrenol monotherapy and in combination with testosterone esters is effective, safe, and inexpensive; however, suppression of gonadotropins is incomplete. Regular blood controls allow screening for unphysiological changes in safety parameters or hormonal levels and for medication abuse.

Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

Context Standardized description of external genitalia is needed in the assessment of children with atypical genitalia. Objectives To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs). Design, Setting A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018. Patients and Methods EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0–12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0–24 months) and 181 preterm babies, and 111 babies with atypical genitalia. Results The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6–11.5); in males 28–32 weeks 11.5 (9.2–12); in males 33–36 weeks 11.5 (10.5–12) and in full-term males 12 (10.5–12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia. Conclusions EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research.

Background: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. Aims: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. Methods: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). Results: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. Conclusion: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.