General discussion 269 2016; Paunio et al., 2015; Pillai et al., 2011). Studies also show that sleep is dysregulated in those with a current depressive disorder, finding increased insomnia symptoms, poor sleep, dysregulation of SWS and REM sleep and later chronotypes (Antypa et al., 2016; Palagini et al., 2013; Pillai et al., 2011; Riemann et al., 2001). In Chapter 1, we hypothesized that adverse changes in sleep after sex hormone interventions, including OCs and GAHT, would be associated with increased risk of depression and more severe depressive symptoms, but as described in this thesis, we could not confirm our hypothesis. Group-level estimations in Chapter 2 show that participants on OCs report slightly higher insomnia severity than non-users, without concurrent increases in depressive symptoms and no association with lifetime history of depression. In participants starting masculinizing GAHT, we find shorter SWS, earlier REM and prolonged REM sleep and a later chronotype, but no increases in depressive symptoms. One could still hypothesize that the effect of adverse changes in sleep, including changes in sleep architecture and chronotype, might have long-term effects on depressive symptoms, implying that the changes in sleep after 3 months of masculinizing GAHT would take longer to affect depression. However, we also find no significant increases in depression after 12 months of masculinizing GAHT in Chapter 3. There could be a number of explanations for these findings. Firstly, it could be that the adverse changes in sleep are more likely to be detected in persons with relatively severe depressive symptoms. As shown in Chapter 3, most study participants in our cohorts reported no or mild depressive symptoms, and in the first 12 months of GAHT, we find no significant changes in prevalence of moderate or severe depression. This low prevalence of severe depression, combined with small cohorts in our studies on sleep architecture and chronotype, could have reduced the likelihood of finding specific depression-associated changes in sleep. A second explanation for the found lack of associations between sleep and depression might stem from psychosocial factors in our studies, and especially in the work on GAHT. Transgender people are likely to suffer from high rates of minority stress (Collet et al., 2023), and it is more common for them to experience social rejection and discrimination (Verbeek et al., 2020). Therefore, we could hypothesize that the participants in the studies on GAHT could report more severe depressive symptoms due to the high
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