Medical Side Effects of GnRH Agonists

Standards of care endorse the use of gonadotropin-releasing hormone (GnRH) agonists for early pubertal gender dysphoric youth. While currently available mental health outcomes data support these recommendations, there are potential adverse effects of such treatment, including impaired bone mineralization, compromised fertility, and unclear effects on brain development, body mass index (BMI), and body composition. Published studies indicate that an expected slowing of bone mineral acquisition during pubertal suppression may not fully recover to baseline after cross-sex hormone therapy within the confines of those treatment models, particularly in transgender females. With respect to brain development, a cross-sectional study showed no adverse effects of GnRH agonists on executive functioning in gender dysphoric adolescents, while a single case report described a small drop in operational memory associated with GnRH agonist treatment. Although GnRH agonist treatment alone does not affect fertility, its use in early pubertal children, followed by cross-sex hormones, will compromise fertility due to arrested gonadal maturation. Finally, GnRH agonists may increase BMI and fat percentages in some gender dysphoric individuals. Further prospective studies focused on long-term safety and efficacy are necessary to optimize GnRH agonist treatment of early pubertal gender dysphoric youth.