Back to the Future: Is GnRHa treatment in transgender and gender diverse adolescents only an extended evaluation phase?

Purpose: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during GnRH analogs (GnRHa) treatment in Transgender and gender diverse adolescents (TGDA). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. Methods: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by Triptorelin prescription referring to the Florence Gender Clinic. This study consisted of three time points: first referral (T0), psychological assessment (T1); treatment with intramuscular injections of Triptorelin for three up to twelve months (T2). Psychometric questionnaires were administered at each time, clinical and biochemical evaluations were performed at T1 and T2. Results: The following results were found: (i) GnRHa showed efficacy in inhibiting puberty progression in TGDA; (ii) an increase in psychopathology was observed before starting GnRHa (T1) as compared to baseline levels; (iii) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression and anxiety levels were observed; (iv) hormone and physical changes (in terms of gonadotropin and sex steroids levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during Triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety and body image concerns. Conclusions: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by GnRHa. Therefore, the rationale for treatment with GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDA whose puberty has already progressed.