Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

• Published in: The journal of clinical endocrinology and metabolism 2024-05, Vol.109 (6), p.1565-1579
• Main Authors: Fisher, Alessandra D, Ristori, Jiska, Romani, Alessia, Cassioli, Emanuele, Mazzoli, Francesca, Cocchetti, Carlotta, Pierdominici, Marina, Marconi, Matteo, Ricca, Valdo, Maggi, Mario, Vignozzi, Linda, Castellini, Giovanni
• Format: Article
• Language: English
• Subjects: Acne; Adolescent; Adolescents; Anxiety; Body image; Body mass index; Female; Gender; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropins; Humans; Male; Pituitary (anterior); Prospective Studies; Psychological assessment; Psychopathology; Puberty; Puberty - drug effects; Puberty - physiology; Puberty - psychology; Sex ratio; Sex Reassignment Procedures - methods; Suicides & suicide attempts; Teenagers; Transgender persons; Transgender Persons - psychology; Transsexualism - drug therapy; Transsexualism - psychology; Triptorelin Pamoate - administration & dosage; Triptorelin Pamoate - therapeutic use; Well being
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgad729

Abstract Context The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. Objective The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). 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 after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. Results The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid 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. Conclusion Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a 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 TGDAs whose puberty has already progressed.