ESPE Yearbook of Paediatric Endocrinology

Brief summary: A four centre prospective longitudinal study of 315 transgender and non-binary adolescents in the USA showed improvement in gender congruence and appearance and some reduction of depression and anxiety (but not in birth-registered males) after 2 years of gender affirming hormone (GAH) treatment.

The race is on to provide clear evidence to support hormonal intervention for transgender adolescents. This longitudinal study employed a number of standard measures (Transgender Congruence Scale, the Beck Depression Inventory–II, the Revised Children’s Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery. Although there was an overall increase in functional measures, this was not universal with an unexplained greater effect in those registered female at birth (60.3%). 24 subjects were in early puberty when GAH were commenced, and they showed a greater increase in life satisfaction.

In a similar but smaller study, Lavender et al. reported retrospectively on 38 transgender adolescents referred to endocrinology younger than 15 years who received GnRHa followed by GAH treatment (1). Measures included the Youth Self Report, the Body Image Scale, and the Utrecht Gender Dysphoria Scale, and caregivers completed the Child Behaviour Checklist and the Social Responsiveness Scale-2. Similar to the US study, dissatisfaction with primary sexual characteristics, gender dysphoria, and social motivation improved significantly over time. Self-harm and suicidality decreased. Caregivers reported a significant reduction in internalizing behaviours after GnRHa.

In another study, Morningstar et al. attempted to explore how GAH influence neurocognitive development by using functional MRI scanning to assess responses to verbal cues in 44 transgender boys with a mean age of 15.8 years, and encountered a direct effect of testosterone sensitising emotional responses to caregivers and a causing a quicker rise to anger to their peer challenges, these effects not being found in the control cohort (2).

Concerns are also raised on the negative potential effects of hormonal intervention on academic performance. Arnoldussen et al. performed IQ tests on 72 trans adolescents at mean of 12.8 years and compared this with their educational achievement at 20.4 years, all having received GnRHa and GAH (3). They found a positive association between IQ and education status with no discernible negative effect of treatment on academic performance.

All these papers, amongst others, are attempting to study the neuropsychological effects of hormonal intervention in transgender adolescents, but it is clear there is no one single assessment that can give answers to all the questions in this area.

References: 1. Lavender R, Shaw S, Maninger JK, Butler G, Carruthers P, Carmichael P, Masic U. Impact of Hormone Treatment on Psychosocial Functioning in Gender-Diverse Young People. LGBT Health. 2023 Mar 28. doi: 10.1089/lgbt.2022.0201. Epub ahead of print. PMID: 36989498. 2. Morningstar M, Thomas P, Anderson AM, Mattson WI, Nahata L, Leibowitz SF, Chen D, Strang JF, Nelson EE. Exogenous testosterone administration is associated with differential neural response to unfamiliar peer’s and own caregiver’s voice in transgender adolescents. Dev Cogn Neurosci. 2023 Feb;59:101194. doi: 10.1016/j.dcn.2022.101194. Epub 2022 Dec 31. PMID: 36634500; PMCID: PMC9841356. 3. Arnoldussen M, Hooijman EC, Kreukels BP, de Vries AL. Association between pre-treatment IQ and educational achievement after gender-affirming treatment including puberty suppression in transgender adolescents. Clin Child Psychol Psychiatry. 2022 Oct;27(4):1069–1076. doi: 10.1177/13591045221091652. Epub 2022 May 31. PMID: 35638479; PMCID: PMC9574895.