Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones

Sebastian E. E. Schagen, Femke M. Wouters, Peggy T. Cohen-Kettenis, Louis J. Gooren, Sabine E. Hannema

Research output: Contribution to journalArticleAcademicpeer-review


CONTEXT: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. OBJECTIVE: To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. DESIGN: Observational prospective study. SUBJECTS: 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. MAIN OUTCOME MEASURES: Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. RESULTS: At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. CONCLUSIONS: BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.
Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number12
Publication statusPublished - 1 Dec 2020

Cite this