Trajectories of Adolescents Treated with Gonadotropin-Releasing Hormone Analogues for Gender Dysphoria

Gonadotropin-releasing hormone analogues (GnRHa) are recommended as initial treatment for adolescents diagnosed with gender dysphoria, providing time to follow gender identity development and consider further treatment wishes without distress caused by unwanted pubertal changes. This has been described as an extended diagnostic phase. However, there are also concerns about the physical, neurocognitive, and psychosocial effects of this treatment. In this retrospective study, we document trajectories after the initiation of GnRHa and explore reasons for extended use and discontinuation of GnRHa. Treatment was considered appropriate in 143 (67%) of the 214 adolescents eligible for GnRHa treatment by virtue of their age/pubertal status, and all started GnRHa (38 transgirls, 105 transboys; median age, 15.0 years [range, 11.1-18.6] and 16.1 years [range, 10.1-17.9]). After a median duration of 0.8 years (0.3-3.8) on GnRHa, 125 (87%) started gender-affirming hormones (GAH). Nine (6%) discontinued GnRHa, five of whom no longer wished gender-affirming treatment. Thirteen had used GnRHa for longer than required by protocol for reasons other than logistics and regularly met with a mental health professional during this time, supporting the use of GnRHa treatment as an extended diagnostic phase. In conclusion, the vast majority who started GnRHa proceeded to GAH, possibly due to eligibility criteria that select those highly likely to pursue further gender-affirming treatment. Due to the observational character of the study, it is not possible to say if GnRHa treatment itself influenced the outcome. Few individuals discontinued GnRHa, and only 3.5% no longer wished gender-affirming treatment.