Changes in depression symptom profile with gender-affirming hormone use in transgender persons 71 1. Introduction There is a known sex difference in depression: cisgender women are twice as likely to experience depression in their lifetime compared to cisgender men (Kuehner, 2003). There are indications that biological factors underlie this increased risk of depression in women. Recent advances in the field of reproductive psychiatry point to a possible role of sex hormones in the risk of mood disorders (Schweizer-Schubert et al., 2021), as illustrated in the female lifespan, in which the risk of depression increases in life phases when female sex hormones fluctuate, such as pregnancy and perimenopause (Soares & Zitek, 2008). Furthermore, cisgender females also show mood changes after exogenous hormone interventions (Eisenlohr-Moul et al., 2023; Frokjaer, 2020). The clinical symptomatology of depression also seems to differ between cisgender men and women. Cisgender women show higher prevalence and severity of symptoms of “atypical depression” (e.g. more weight gain, increased appetite, hypersomnia, and interpersonal sensitivity) while cisgender men report more symptoms of melancholic depression, such as severe anhedonia and low mood (Khan et al., 2006), and more psychomotor agitation (Marcus et al., 2005; Schuch et al., 2014). Data-driven analyses have provided insight into symptom profiles of depression: using analyses such as Exploratory Factor Analysis (EFA), researchers have identified underlying dimensions of depressive symptoms. These symptom dimensions, also called clusters, can also be used as questionnaire subscales. Previous studies showed population differences between symptom clusters: EFA in a clinically depressed population showed four symptom clusters for mood-, anxiety-, somatic- and sleep-related symptoms (Wardenaar et al., 2010), whereas, for instance, EFA in an elderly cohort has shown three symptom clusters for mood, motivation, and somatic symptoms (Hegeman et al., 2012). A subpopulation for whom the effect of sex hormones on depression is especially relevant is the transgender population. Transgender persons’ gender identity is not in line with their sex assigned at birth, which can result in gender dysphoria. Gender-affirming hormone therapy (GAHT) can reduce this incongruence between gender identity and physical features:
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