Abstract
ContextHormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual.ObjectiveTo describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones.DesignObservational prospective study.Subjects51 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 MeasuresBone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers.ResultsAt 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.ConclusionsBMAD 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.
Highlights
Context: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual
We set out to describe the course of bone mineral density (BMD) during 2 years of gonadotropin-releasing hormone analogues (GnRHa) therapy and during 3 years of subsequent gender-affirming hormone treatment in a large group of adolescents diagnosed with gender dysphoria, with measurements at yearly intervals
From 45 subjects, some data were included in previous studies by Vlot et al (8) and Klink et al (10), but those studies only reported results at 3 time points: at the start of GnRHa, at the start of gender-affirming hormones, and after 2 years of genderaffirming hormones (8) or age 22 years (10), and they did not describe a detailed course of BMD and bone markers over several years of GnRHa or gender-affirming hormone treatment
Summary
Context: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. Three studies in adolescents diagnosed with gender dysphoria receiving GnRHa and gender-affirming hormone treatment reported decreases in areal BMD (aBMD) and bone mineral apparent density (BMAD) z-scores during GnRHa treatment, not all significant (8-10). One study investigated bone markers and showed a decrease of carboxyterminal cross-linked telopeptide of type I collagen (1CTP) and N-terminal propeptide of type-1 collagen (P1NP) during GnRHa and during subsequent gender-affirming hormone treatment which was interpreted as evidence of decreased bone turnover (8). All these studies compared data at the start of GnRHa treatment, at the start of gender-affirming hormones and one endpoint, either 12–24 months after the start of gender-affirming hormone therapy or age 22 years. We report data from a small subgroup with more prolonged GnRHa treatment
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