Project Summary The proposed project examines the effects of pubertal suppression treatment on the mental health of transgender adolescents over time. The physical changes brought on by puberty often amplify gender dysphoria in transgender youth. Administering gonadotropin releasing hormone agonists (GnRHa) is an effective means of suppressing puberty to provide transgender youth, their families, and health care teams more time to consider whether partially and/or fully irreversible treatments are indicated. Pubertal suppression is endorsed by the World Professional Association for Transgender Health and the Endocrine Society as standard of care. Preliminary reports suggest that treatment with GnRHa may confer mental health benefits for transgender youth. However, GnRHa may also disrupt puberty-signaled neural maturation in ways that can undermine mental health gains over time and impact quality of life in other ways. The overall impacts of GnRHa treatment have not been systematically studied. In order to probe these effects, this project focuses on the assessment of dimensional mental health and three neural systems that map onto the NIMH RDoC matrix: cognitive/emotional control, social cognition, and reward responsiveness. Existing literature documents marked maturation in these systems during normative adolescent development, and gonadal hormones are thought to contribute to this maturation. We will take a multimodal approach, in which self- and parent-report, standardized neuropsychological assessments, and neuroimaging methods are used to assess the effects of GnRHa treatment over a two-year study period. We will enroll 132 transgender adolescents across three sites: Nationwide Children’s Hospital; Children’s National Hospital; and Lurie Children’s Hospital. Half will be undergoing pubertal suppression with GnRHa and the other half will be transgender youth not undergoing treatment. Evaluating the impact of GnRHa treatment on mental health functioning as well as puberty-linked RDoC system maturation will clarify its potential protective and risk effects to support optimization and personalization of treatment protocols.

Project Narrative This project aims to define the impact of pubertal suppression treatment in transgender youth on mental health trajectories and underlying neural systems. By comparing transgender youth who receive pubertal suppression treatment to those who do not, with repeated assessments over time, we seek to identify patterns of improvement and/or worsening in each group. The information gained from this project will inform the optimization of standard of care pubertal suppression treatment.