Changes in depression symptom profile with gender-affirming hormone use in transgender persons 73 This study aimed to address symptom profiles of depression in transgender persons and the influence of GAHT. The first aim was to examine depression symptom profile just before the start of GAHT and to compare the profiles between TM and TF persons. The second aim was to study the effect of GAHT, by studying the changes in symptom profiles after 3 and 12 months of GAHT, and assessing whether these significantly differ between TM and TF participants. Based on population differences in cisgender populations, we hypothesize that before GAHT, the TM group will report more symptoms of atypical depression (e.g. increase in appetite and weight, higher interpersonal sensitivity, and hypersomnia) and that the TF group will report more severe anhedonia and low mood. After starting GAHT, we hypothesize that the severity of depressive symptoms will decrease in both groups due to psychosocial effects of GAHT, but that, the TM group will show a stronger decrease in overall depressive symptoms and a stronger decrease in atypical symptoms than the TF group due to biological effects of GAHT. 2. Methods 2.1. Study setting We used data from two studies: the European Network for the Investigation of Gender Incongruence (ENIGI) study and the Relationship between Emotions and Sleep in Transgender persons: Endocrinology and Depression (RESTED) study. The ENIGI-endocrinology study is a multi-center cohort study that examines the effects of GAHT (Dekker et al., 2016), conducted at five treatment centers (Ghent, Florence, Tel Aviv, Oslo, and Amsterdam). Because of logistical reasons, the ENIGI data for this study was only collected in Amsterdam at the Amsterdam University Medical Center (Amsterdam UMC, location VU medical center) from January 2020 to July 2022. The RESTED study aims to study changes in sleep architecture, insomnia, and depression after GAHT. It is a multi-center study involving Amsterdam UMC and University Medical Center Groningen (UMCG). The RESTED data for this study were collected between January 2020 and August 2022. Both studies received a declaration from the Medical Ethics Review Committee of the VU medical center stating that Medical Research Involving Human Subjects Act (WMO) did not apply to the studies (ENIGI: study id. 2019.469 and RESTED:
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