The review concluded that the long-term effects of hormone therapy on psychosocial health could not be evaluated due to lack of studies with sufficient quality. Concerning bone health, GnRHa treatment delays bone maturation and bone mineral density gain that, however, seem to partially recover during cross-sex hormone therapy when studied at age 22 years.

“Our work is important not only because the incidence of young people with gender dysphoria has increased during a short period of time, but also because of the change in case-mix. We do not know what the natural trajectory is for these children. Studies should first elucidate to what extent gender dysphoria spontaneously remit in adolescents who have not presented gender incongruent behavior in childhood. If predictors for persistence can be found, the second step would be to conduct clinical trials focusing on potential persisters in order to evaluate the beneficial and adverse effects of hormonal treatments. Importantly, such studies need to follow patients for many years”, says corresponding author Professor Mikael Landén, at Karolinska Institutet and University of Gothenburg. “Against the background of almost non-existent longterm data, we conclude that GnRHa treatment in children with gender dysphoria should be considered experimental treatment rather than standard procedure. This is to say that treatment should only be administered in the context of a clinical trial under informed consent”, he adds.

“We found substantial limitations in earlier research on gender dysphoria, and the few longitudinal observational studies were hampered by small numbers, and high attrition rates”, adds Ludvigsson. “For that reason we created a checklist, the GENDHOR checklist, that we hope will facilitate and increase the quality of future research in this field.”

Note

The GENDHOR checklist can be found in the manuscript.

Funding

The Swedish agency for health technology assessment and assessment of social services

Conflicts of interest

Dr Ludvigsson has coordinated an unrelated study on behalf of the Swedish inflammatory bowel disease quality register (SWIBREG) that received funding from the Janssen Corporation. JFL has also received financial support from Merck Sharp & Dohme developing a paper reviewing national healthcare registers in China. JFL is currently discussing potential research collaboration with Takeda. ML has received lecture honoraria from Lundbeck pharmaceuticals.

For more information, please contact

Mikael Landén, professor, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University of Gothenburg

Email: mikael.landen@ki.se or Mikael.Landen@neuro.gu.se

Publication

A systematic review of hormone treatment for children with gender dysphoria and recommendations for research.

Ludvigsson JF, Adolfsson J, Höistad M, Rydelius PA, Kriström B, Landén M

Acta Paediatr 2023 Apr 18.