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

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 12; pp. e4252 - e4263
• Main Authors: Schagen, Sebastian E E, Wouters, Femke M, Cohen-Kettenis, Peggy T, Gooren, Louis J, Hannema, Sabine E
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.12.2020; Copyright Oxford University Press
• Subjects: Adolescent; Adolescent Development - drug effects; Adolescent Development - physiology; Adolescents; Age; Bone Density - drug effects; Bone Development - drug effects; Bone Development - physiology; Bone mass; Bone mineral density; Bones; Child; Clinical s; Estrogens; Female; Gender; Gender dysphoria; Gender Dysphoria - drug therapy; Gender Dysphoria - physiopathology; Gonadotropin releasing hormone; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - pharmacology; Gonadotropin-Releasing Hormone - therapeutic use; Gonadotropins; Growth; Health aspects; Hormone Replacement Therapy - methods; Hormones; Hormones, Sex; Humans; Male; Minority teenagers; Minority youth; Netherlands; Pituitary (anterior); Prospective Studies; Sex Reassignment Procedures; Sexual Maturation - drug effects; Teenagers; Testosterone - pharmacology; Testosterone - therapeutic use; Transgender people; Transsexualism - drug therapy; Transsexualism - physiopathology; Triptorelin Pamoate - pharmacology; Triptorelin Pamoate - therapeutic use; Netherlands; bone mineral density; sex steroids; adolescents; gender dysphoria; bone; GnRH analogue; transgender
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa604

Abstract 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.