Abstract

Background and Objectives Medical interventions for youth with gender dysphoria can include the use of gonadotropin releasing hormone analogs (GnRHas) for suppression of endogenous puberty. This analysis aimed to understand the impact of medical intervention initiated with GnRHas on psychological well-being among youth with gender dysphoria over 24 months.

Methods Participants were enrolled as part of the Trans Youth Care United States Study. Eligibility criteria for youth included a diagnosis of Gender Dysphoria and pubertal initiation. Youth with precocious puberty or pre-existing osteoporosis were ineligible. Youth reported on depressive symptoms, emotional health and suicidality at baseline, 6, 12, 18 and 24 months after initiation of GnRHas. Parent/caretaker completed the Child Behavior Checklist at baseline, 12 and 24 months after initiation of GnRHas. Latent Growth-Curve Models analyzed trajectories of change over the 24-month period.

Results Ninety-four youth aged 8-16 years (mean=11.2 y) were predominately Non-Hispanic White (56%), early pubertal (86%) and assigned male at birth (52%). Depression symptoms, emotional health and CBCL constructs did not change significantly over 24 months. At no time points were the means of depression, emotional health or CBCL constructs in a clinically concerning range.

Conclusion Participants initiating medical interventions for gender dysphoria with GnRHas have self- and parent-reported psychological and emotional health comparable with the population of adolescents at large, which remains relatively stable over 24 months. Given that the mental health of youth with gender dysphoria who are older is often poor, it is likely that puberty blockers prevent the deterioration of mental health.

What’s known on this subject Puberty blockers are effective in halting endogenous puberty and prior research suggests improved mental health in youth with gender dysphoria. Few studies originate from the United States and most include older youth in later stages of puberty at initiation of blockers.

What this study adds This is the largest longitudinal cohort of youth with gender dysphoria initiating medical intervention beginning with puberty blockers in early puberty to be followed in the United States. Youth demonstrated both stability and improvement in emotional and mental health over 24 months.

Contributors Statement Page Dr. Olson-Kennedy conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript.

Dr. Durazo-Arvizu carried out follow-up analyses and critically reviewed the manuscript.

Drs. Garofalo, Rosenthal, Chan, Chen, Ehrensaft, and Hidalgo conceptualized and designed the study, and critically reviewed and revised the manuscript.

Drs. Wang and Wong carried out the initial analyses and critically reviewed and revised the manuscript.

Dr. Radix critically reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Protocols

https://www.researchprotocols.org/2019/7/e14434/

Funding Statement

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD082554). Study sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the article for publication.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board at Childrens Hospital Los Angeles gave ethical approval for this work The Institutional Review Board at Lurie Childrens Hospital of Chicago gave ethical approval for this work The Institutional Review Board at UCSF Benioff Childrens Hospital gave ethical approval for this work The Institutional Review Board at Boston Childrens Hospital gave ethical approval for this work

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Footnotes

Conflict of Interest Disclosure: The authors have no conflicts of interest relevant to this article to disclose.

Funding/Support: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD082554). Study sponsors had no role in study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the article for publication.

Clinical Trial Registration (if any): none

Data Availability

All data produced in the present study are available upon reasonable request to the authors

Abbreviations:BDI-YBeck Depression Inventory – YouthCBCLChild Behavior ChecklistDSABdesignated sex at birthGAHTgender affirming hormone therapyGnRHagonadotropin releasing hormone agonistNIHTB-EBThe NIH Toolbox Emotion BatteryTYCUSTrans Youth Care United States StudyTNBTransgender and non-binaryWPATHWorld Professional Association of Transgender Health