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Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones
Sebastian E E Schagen1, Femke M Wouters2, Peggy T Cohen-Kettenis3
1Department of Pediatric Endocrinology, VU University Medical Center, 1081 HV Amsterdam, & Leiden University Medical Center, ZA Leiden, the Netherlands.
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.
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