GnRH analogs as a monotherapy in transgender and gender-diverse adolescents: clinical insights from a single-center study.

Background: Gonadotropin-releasing hormone agonists (GnRHas) are widely used in the treatment of transgender and gender-diverse adolescents to prevent the development of undesired physical changes. However, the safety of GnRHa use remains a subject of debate and objective literature on this topic is limited. In particular, there is a lack of studies comparing the effects of GnRHas at different Tanner stages, as the effectiveness of GnRHa treatment in adolescents who are close to completing puberty remains uncertain. Aim: The aim of this study was to evaluate the effects of GnRHa monotherapy in transgender adolescents with gender dysphoria (GD) at early versus late Tanner stages. Methods: This retrospective study analyzed the electronic medical records of adolescents with GD who were treated with GnRHa monotherapy at the Radboudumc Expert Center for Sex & Gender. Treatment duration ranged from 0.5 to 2 years, with follow-up every three months. The outcomes assessed included biometrics, biochemistry, and self-reported side effects. Results: The study included data from 67 assigned females at birth (AFAB) and 33 assigned males at birth (AMAB). A total of 51 adolescents were classified as Tanner stage 2 or 3, and 49 were classified as Tanner stage 4 or 5. 33% of the participants had psychiatric coexisting conditions, most commonly attention deficit hyperactivity disorder (19%) and ASD (18%). In addition, 36% of the adolescents were either overweight or obese. During follow-up, gonadotropin levels were not fully suppressed, particularly in the Tanner 4/5 group, while sex hormone levels were suppressed in nearly all adolescents. Side effects, especially hot flushes, abdominal discomfort, and emotional disturbances, were significantly more common in the Tanner 4/5 group, with 76% of this group reporting hot flushes. The impact of GnRHa treatment on pubertal development was minimal. Overweight and psychiatric comorbidities were prevalent among the adolescents. Conclusion: GnRHas effectively suppressed sex hormone levels in adolescents with GD, although gonadotropin suppression was not complete, particularly in the Tanner 4/5 group, where gonadotropin levels remained elevated. Side effects were frequently reported, particularly in the Tanner 4/5 group, while the impact on pubertal development was limited. Therefore, the benefits and drawbacks of GnRHa treatment should be carefully considered, particularly in adolescents at Tanner stages 4 and 5.