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 in 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 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 two years of GnRHa treatment BMAD stabilized or showed a small decrease, whereas Z-scores decreased in all groups. During three years of combined administration of GnRHa and gender affirming hormones, a significant increase of BMAD was found. Z-scores normalised 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 three years of estrogen treatment. If this results in adverse outcomes such as increased fracture risk in transgirls as they grow older is currently unclear.
Introduction In the literature, verbal fluency (VF) is generally described as a female-favoring task. Although it is conceivable that this sex difference only evolves during adolescence or adulthood under influence of sex steroids, this has never been investigated in young adolescents. Aim First, to assess sex differences in VF performance and regional brain activation in adolescents. Second, to determine if untreated transsexual adolescents differ from their sex of birth with regard to VF performance and regional brain activation. Method Twenty-five boys, 26 girls, 8 Male-to-Female transsexual adolescents (MtFs), and 14 Female-to-Male transsexual adolescents (FtMs) were tested in a cross-sectional study, while performing a phonetic and semantic VF task within an MRI scanner. Main Outcome Measures Functional MRI response during VF task. Results Boys and girls produced similar amounts of words, but the group MtFs produced significantly more words in the phonetic condition compared to control boys, girls, and FtMs. During the semantic condition, no differences were found. With regard to brain activity, control boys showed more activation in the right Rolandic operculum, a small area adjacent to Broca's area, compared to girls. No significant differences in brain activity were found comparing transsexual adolescents, although sub-threshold activation was found in the right Rolandic operculum indicating a trendwise increase in activation from control girls to FtMs to MtFs to control boys. Conclusions The better performance of MtFs is consistent with our expectation that MtFs perform better on female-favoring tasks. Moreover, they produced more words than girls and FtMs. Even though a trendwise linear increase in brain activity between the four groups only approached significance, it may indicate differences in individuals with gender identity disorder compared to their birth sex. Although our findings should thus be interpreted with caution, they suggest a biological basis for both transgender groups performing in-between the two sexes.
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