98 Chapter 5 Challenges when assessing medical decision-making competence to start puberty suppression Several aspects the participants mentioned illustrate ethical challenges surrounding assessing adolescents’ MDC to start PS. One of these aspects is the fact that certain consequences of PS and uncertainty about long-term effects cause doubts. Similar ethical challenges play a role in other fields. For example, in children with limited treatment options for serious conditions, ‘experimental’ interventions such as gene therapy may be seen as the best available option (Lyer et al., 2021). GnRHa are used as standard care for children with precocious puberty and an increasing number of other indications, and adverse psychological and physical effects have been rare (Krishna et al., 2019; Lee et al., 2014; Yu, Yang, & Hwang, 2019). Nevertheless, several adolescents, parents and clinicians in the current study share a feeling of unease regarding PS. They try to find a balance between the need to relieve the distress associated with the undesired endogenous pubertal development of the transgender adolescent, and the wish to avoid potential long-term negative effects of PS (Butler, Wren, & Carmichael, 2019). This is difficult since what the best care is, depends also on individual preferences. Even though more evidence-based outcomes of treatment is important, it remains impossible to predict the treatment’s effects and impact on a particular individual. One of the consequences mentioned by the participants was the possible loss of fertility. Interestingly, several adolescents, most of whom were continuers, parents, and all clinicians had a specific feeling of unease about this. One could therefore question to what extent or in what way potential loss of fertility should already be taken into account when assessing adolescents’ MDC to start PS. Although the effects of PS on the development of secondary sex characteristics and gonadal function are reversible when the treatment is discontinued, as far as is currently known, if adolescents subsequently undergo treatment with GAH and gonadectomy, this will result in loss of fertility (Hembree et al., 2017). If they start PS at a young age, they may never undergo their endogenous puberty and may therefore not be able to pursue fertility preservation (Brik et al., 2019; Hudson et al., 2018). However, not all adolescents pursue gonadectomy, and depending on birth-assigned sex and the type of treatment individuals choose to undergo, fertility outcomes may vary (Cheng, Pastuszak, Myers, Goodwin, & Hotaling, 2019). Research shows that very few (1.9-6%) adolescents discontinue PS (e.g. Brik et al., 2020; Khatchadourian, Amed, & Metzger, 2014; Wiepjes et al., 2018). A subset of these adolescents (3.5-3.7%) no longer wish gender-affirming medical treatment (GAMT) (Brik et al., 2020, Khatchadourian et al., 2014). That means that the vast majority of the adolescents who start PS subsequently proceed to GAH, with possible loss of fertility as a result. Providing adequate information about the impact of treatment on future fertility and about fertility preservation is therefore highly recommended (Armuand, Wettergren, Rodriguez-Wallberg, & Lampic, 2014; Stein et al., 2014).