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Competing Interests: Declaration of Competing Interest Dr. Sequeira has received compensation for Pivotal Ventures for participation in an advisory board. Dr. McNamara has received expert witness payments from Human Rights Campaign and GLBTQ Defenders. The other authors have no relevant disclosures. No sources of funding.

Objective: To assess the odds of a psychiatric or neurodevelopmental diagnosis among youth with a diagnosis of gender dysphoria compared with matched controls in a large electronic health record dataset from 6 pediatric health systems, PEDSnet. We hypothesized that youth with gender dysphoria would have higher odds of having psychiatric and neurodevelopmental diagnoses than controls., Study Design: All youth with a diagnosis of gender dysphoria (n = 4173 age at last visit 16.2 ± 3.4) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables to controls without gender dysphoria (n = 16 648, age at last visit 16.2 ± 4.8) using multivariable logistic regression. The odds of having psychiatric and neurodevelopmental diagnoses were examined using generalized estimating equations., Results: Youth with gender dysphoria had higher odds of psychiatric (OR 4.0 [95% CI 3.8, 4.3] P < .0001) and neurodevelopmental diagnoses (1.9 [1.7, 2.0], P < .0001). Youth with gender dysphoria were more likely to have a diagnosis across all psychiatric disorder subcategories, with particularly high odds of mood disorder (7.3 [6.8, 7.9], P < .0001) and anxiety (5.5 [5.1, 5.9], P < .0001). Youth with gender dysphoria had a greater odds of autism spectrum disorder (2.6, [2.2, 3.0], P < .0001)., Conclusions: Youth with gender dysphoria at large pediatric health systems have greater odds of psychiatric and several neurodevelopmental diagnoses compared with youth without gender dysphoria. Further studies are needed to evaluate changes in mental health over time with access to gender affirming care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The number of gender diverse and transgender youth presenting for treatment are increasing. This is a vulnerable population with unique medical needs; it is essential that all pediatricians attain an adequate level of knowledge and comfort caring for these youth so that their health outcomes may be improved. There are several organizations which provide clinical practice guidelines for the treatment of transgender youth including the WPATH and the Endocrine Society and they recommend that certain eligibility criteria should be met prior to initiation of gender affirming hormones. Medical intervention for transgender youth can be broken down into stages based on pubertal development: pre-pubertal, pubertal and post-pubertal. Pre-pubertally no medical intervention is recommended. Once puberty has commenced, youth are eligible for puberty blockers; and post-pubertally, youth are eligible for feminizing and masculinizing hormone regimens. Treatment with gonadotropin releasing hormone agonists are used to block puberty. Their function is many-fold: to pause puberty so that the youth may explore their gender identity, to delay the development of (irreversible) secondary sex characteristics, and to obviate the need for future gender affirmation surgeries. Masculinizing hormone regimens consists of testosterone and feminizing hormone regimens consist of both estradiol as well as spironolactone. In short term studies gender affirming hormone treatment with both estradiol and testosterone has been found to be safe and improve mental health and quality of life outcomes; additional long term studies are needed to further elucidate the implications of gender affirming hormones on physical and mental health in transgender patients. There are a variety of surgeries that transgender individuals may desire in order to affirm their gender identity; it is important for providers to understand that desire for medical interventions is variable among persons and that a discussion about individual desires for surgical options is recommended., (Copyright © 2019 Elsevier Inc. All rights reserved.)