The safety and efficacy of the Dutch Protocol is highly debated. Among the concerns regarding long-term safety of puberty suppression is a potential harmful effect on BMD accrual. Furthermore, the recent, unexplained, rise in predominantly AFAB referrals poses the question whether this particular group is different to former individuals. This could apply to personal traits, such as age and co-occurrence of psychological conditions, as well as characteristics of gender dysphoria, such as age at onset. The objective of this thesis was to shed light on outcomes in children and adolescents referred to the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Amsterdam, the clinic where the Dutch Protocol originated. This thesis aims to: 1. Investigate treatment trajectories of the population of children and adolescents referred to our gender identity clinic, including possible discontinuation of treatment. 2. Investigate the long-term effect of the combined treatment with puberty suppression and GAH on bone health, by studying the development of BMD in transgender adolescents with and without medical intervention, and changes in bone geometry. Outline In Part 1 of this thesis a general description of the children and adolescents who were referred for evaluation of gender dysphoria and/or treated according to the Dutch Protocol is given. Chapter 2 provides a broad overview of trajectories in these referred individuals. Besides trends in demographics of referred people, it describes the proportions of adolescents starting and stopping puberty suppression, and reasons for refraining from puberty suppression. In Chapter 3 the rate of discontinuation of GAH in people treated according to the Dutch Protocol is assessed. Part 2 addresses bone development in people diagnosed with gender dysphoria in puberty. In Chapter 4 BMD development is analyzed in individuals during puberty suppression and gender-affirming treatment, and after long-term use of GAH. Chapter 5 studies whether the effect of estrogen on BMD is dose-dependent in trans girls. The natural course (i.e. prior to any medical treatment) of BMD development in adolescents diagnosed with gender dysphoria is studied in Chapter 6. Chapter 7 investigates the changes in bone geometry during treatment. The main findings of all studies are discussed in Chapter 8.
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