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

J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4252-e4263. 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.

Keywords: GnRH analogue; adolescents; bone; bone mineral density; gender dysphoria; sex steroids; transgender.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adolescent Development / drug effects
  • Adolescent Development / physiology
  • Bone Density / drug effects
  • Bone Development / drug effects*
  • Bone Development / physiology
  • Child
  • Female
  • Gender Dysphoria / drug therapy*
  • Gender Dysphoria / physiopathology
  • Gender-Affirming Procedures
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / pharmacology
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Hormone Replacement Therapy* / methods
  • Humans
  • Male
  • Netherlands
  • Prospective Studies
  • Sexual Maturation / drug effects
  • Testosterone / pharmacology
  • Testosterone / therapeutic use
  • Transsexualism / drug therapy*
  • Transsexualism / physiopathology
  • Triptorelin Pamoate / pharmacology
  • Triptorelin Pamoate / therapeutic use

Substances

  • Triptorelin Pamoate
  • Gonadotropin-Releasing Hormone
  • Testosterone

Associated data

  • ISRCTN/ISRCTN81574253