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

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.

Figure 1.

Estimated marginal means and standard error of the mean of BMAD prior to and during 2 years of GnRHa administration in transgirls and transboys. Significant changes during the 2 years of GnRHa administration are indicated by an asterisk. Abbreviations: BMAD: bone mineral apparent density; FM, femoral neck; LS, lumbar spine.

Figure 2.

Estimated marginal means and negative standard error of the mean of osteocalcin, P1NP, P3NP, and 1CTP prior to and during 2 years of GnRHa administration in transgirls and transboys. Significant changes during the 2 years of GnRHa administration are indicated by asterisk.

Figure 3.

Estimated marginal means and standard error of the mean of BMAD prior to and during 3 years of GnRHa + gender-affirming treatment in transgirls and transboys. Significant changes during the 3 years of GnRHa + gender-affirming treatment are indicated by an asteriks.

Figure 4.

Estimated marginal means and standard error of the mean of osteocalcin, P1NP, P3NP, and 1CTP prior to and during 3 years of GnRHa + gender-affirming treatment in transgirls and transboys. Significant changes during the 3 years of GnRHa + gender-affirming treatment are indicated by an asteriks.