Consensus Parameter: Research Methodologies to Evaluate Neurodevelopmental Effects of Pubertal Suppression in Transgender Youth

Abstract

Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment. Methods: A Delphi consensus procedure engaged 24 international experts in neurodevelopment, gender development, puberty/adolescence, neuroendocrinology, and statistics/psychometrics to identify priority research methodologies to address the empirical question: is pubertal suppression treatment associated with real-world neurocognitive sequelae? Recommended study approaches reaching 80% consensus were included in the consensus parameter. Results: The Delphi procedure identified 160 initial expert recommendations, 44 of which ultimately achieved consensus. Consensus study design elements include the following: a minimum of three measurement time points, pubertal staging at baseline, statistical modeling of sex in analyses, use of analytic approaches that account for heterogeneity, and use of multiple comparison groups to minimize the limitations of any one group. Consensus study comparison groups include untreated transgender youth matched on pubertal stage, cisgender (i.e., gender congruent) youth matched on pubertal stage, and an independent sample from a large-scale youth development database. The consensus domains for assessment includes: mental health, executive function/cognitive control, and social awareness/functioning. Conclusion: An international interdisciplinary team of experts achieved consensus around primary methods and domains for assessing neurodevelopmental effects (i.e., benefits and/or difficulties) of pubertal suppression treatment in transgender youth.

Assessing Medical Decision-Making Competence in Transgender Youth

“…6 However, there are worries about the impact of PS on physical, cognitive, and psychosocial development and the capability of making decisions about this treatment with profound implications (eg, regarding fertility) at this young age. [9][10][11] Minors' MDC for interventions is a major issue in pediatric ethics. Therefore, according to the international guidelines, one of the criteria for transgender adolescents to start PS is having sufficient mental capacity to give IC.…”

Bell v Tavistock and Portman NHS Foundation Trust [2020] EWHC 3274: Weighing current knowledge and uncertainties in decisions about gender-related treatment for transgender adolescents

“…In contrast, the High Court in London judged the evidence base for gender-related medical treatment for children and adolescents to be "highly uncertain." Both within and outside of the field of transgender health, the relative paucity of scientific evidence is acknowledged (e.g., Byng et al, 2018;Pang et al, 2019) and all involved agree there is a need for further research (Chen et al, 2020a;Olson-Kennedy et al, 2016). An explanation for the lack of studies may be that finding financial resources to conduct long term longitudinal clinical follow up studies is challenging.…”

The role of steroid hormones in the sexual differentiation of the human brain

“…Clearly, larger-scale, longitudinal studies are required to understand possible neurodevelopmental impacts of pubertal suppression over time in transgender youth. 113 Interestingly, the same adolescent MRI sample 100 was used to analyze GM volumes. 114 At the whole-brain level, sex-typical volumes were observed in transgender youth.…”