Gender dysphoria (GD) is diagnosed at increasingly young ages. In children who have GD, puberty
suppression with gonadotropin-releasing hormone agonists is a widely accepted intervention to
avoid development of unwanted sex characteristics. Around the age of 16, cross-sex hormones are
added. Although very often applied, studies on the long-term consequences of this treatment for
general health (growth, bone, body composition, metabolism), especially when given for many
years, are very rare. This project aims to address this gap. We hypothesize that the early phase of
puberty, in which sex differences in height, bone mass, body composition and lipid and glucose
metabolism mostly develop, is irreversibly disturbed due to the long-term suppression of pubertal
sex steroids, and that addition of cross-sex hormones in late puberty can only partially reverse the
phenotype. We will investigate our hypothesis in a number of prospective case-control studies in
transgender youth, and in a preclinical mouse model in which early pubertal steroid deficiency is
induced through ovariectomy, and in which testosterone is added in late puberty. Given the
increasing incidence of childhood GD, we believe that the current project is very timely and
important.