Body Mass Index Distributions and Obesity Prevalence in a Transgender Youth Cohort - A Retrospective Analysis.

PURPOSE: To evaluate differences in auxological parameters between transgender and cisgender adolescents. METHODS: Retrospective analysis of auxological data of 269 transgender and gender diverse patients (75% assigned female at birth or AFAB, 25% assigned male at birth or AMAB) at the outpatient clinic for Pediatric Endocrinology at the Vienna General Hospital. All were treatment naïve at initial measurement. Height and weight data were compared to current World Health Organization (WHO) standards, defining a standard deviation score (SDS) of ≥ 1 ≤ 2 as overweight and > 2 as obese. RESULTS: In our untreated transgender population (mean age 15.7 years), 20% were overweight and 17% obese. Mean BMI was 0.64 SDS above the WHO average (p < .001). This result was more pronounced in the AFAB subgroup (+0.73 SDS, p < .001) than in the AMAB group (+0.37 SDS, p = .07). The AMAB group showed markedly higher BMI variance compared to WHO standards (p < .001) and to the AFAB group (p = .03), due to a higher relative number of underweight observations. When correcting for psychiatric diagnosis, transgender patients were still significantly overweight (p < .001). In patients for whom data both pregender-affirming hormone therapy and during gender-affirming hormone therapy was available (n = 133), BMI SDS did not change significantly over time (p = .22). DISCUSSION: We observed significantly higher rates of overweight and obesity in our adolescent transgender cohort. The reasons are likely complex and multifactorial. This makes eating and exercise behaviors central in both transgender care and future research.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy.

Objective: The aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care. Methods: Patients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes. Results: Of 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker. Conclusion: This is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Lipidation and PEGylation Strategies to Prolong the in Vivo Half-Life of a Nanomolar EphA4 Receptor Antagonist.

The EphA4 receptor tyrosine kinase plays a role in neurodegenerative diseases, inhibition of nerve regeneration, cancer progression and other diseases. Therefore, EphA4 inhibition has potential therapeutic value. Selective EphA4 kinase inhibitors are not available, but we identified peptide antagonists that inhibit ephrin ligand binding to EphA4 with high specificity. One of these peptides is the cyclic APY-d3 (ßAPYCVYRßASWSC-NH2), which inhibits ephrin-A5 ligand binding to EphA4 with low nanomolar binding affinity and is highly protease resistant. Here we describe modifications of APY-d3 that yield two different key derivatives with greatly increased half-lives in the mouse circulation, the lipidated APY-d3-laur8 and the PEGylated APY-d3-PEG4. These two derivatives inhibit ligand induced EphA4 activation in cells with sub-micromolar potency. Since they retain high potency and specificity for EphA4, lipidated and PEGylated APY-d3 derivatives represent new tools for discriminating EphA4 activities in vivo and for preclinical testing of EphA4 inhibition in animal disease models.