Abstract
Purpose: 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.
Highlights
Standards of care established by the World Professional Association for Transgender Health[1] and the Endocrine Society[2] recommend pubertal suppression for gender dysphoric transgender youth during early puberty (i.e., Tanner stages 2–3).[3,4] Pubertal suppression is achieved through administration of gonadotropinreleasing hormone agonists (GnRHa)
A fourth cross-sectional study compared adolescents diagnosed with gender dysphoria (GD), who were treated with GnRHa and close to starting GAH treatment (n = 178), adolescents newly referred for GD evaluation (n = 272), and cisgender adolescents recruited from the general population (n = 651) on selfreported internalizing/externalizing problems, self-harm/ suicidality, and peer relationships.[10]
We identify priority research methodologies that can be used to address the empirical question of how pubertal suppression in transgender youth may affect neurodevelopment and real-world functioning
Summary
Standards of care established by the World Professional Association for Transgender Health[1] and the Endocrine Society[2] recommend pubertal suppression for gender dysphoric transgender youth during early puberty (i.e., Tanner stages 2–3).[3,4] Pubertal suppression is achieved through administration of gonadotropinreleasing hormone agonists (GnRHa). When administered in early puberty, GnRHa suppress endogenous sex hormone production and prevent the development of undesired and irreversible secondary sex characteristics, thereby minimizing distress associated with pubertal development incongruent with gender identity.[5] For youth who later decide to initiate estrogen/testosterone (gender-affirming hormones [GAH]) treatment to induce development of the desired secondary sex characteristics, pubertal suppression may minimize the need for more invasive, surgical interventions (e.g., facial and chest surgery). Three longitudinal studies have examined psychosocial outcomes in GnRHa-treated transgender youth; two (conducted by the same research group) followed a single cohort over time, immediately before initiating GAH (N = 70)[7] and later in early adulthood after surgery for gender affirmation (N = 55).[8] The third study compared groups of GnRHa-treated (n = 35) and untreated (n = 36) youth longitudinally.[9] Findings across these studies include significant reductions in depressive symptoms and improvement in overall psychosocial functioning in GnRHa-treated transgender youth. GnRHa-treated transgender adolescents had fewer emotional and behavioral problems than clinicreferred, untreated adolescents and had comparable or better psychosocial functioning than same-age
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