Chapter 3 72 transmasculine (TM) persons, who were assigned female at birth but want to masculinize their bodies, can use testosterone, and transfeminine (TF) persons, who were assigned male at birth but want to feminize their bodies, can use estradiol and anti-androgens. Although studies generally find a positive effect of GAHT on depression prevalence, the effects of GAHT on the symptom profile of depression are yet unknown. Based on the findings in cisgender persons, it is important to assess whether sex hormones can also change the symptom profiles of depression (i.e. which symptoms or clusters of symptoms change after GAHT) in transgender persons. Prevalence rates for depression in transgender persons, before accessing gender-affirming care, range from 42% to 48% (Aldridge et al., 2021; Colizzi et al., 2014), compared to 8.5% in the cisgender population (Ten Have et al., 2023). One explanation for this improvement is the effects of GAHT on psychosocial well-being, which include improved body image (van de Grift et al., 2017), improved self-esteem (Gorin-Lazard et al., 2012), reduced social distress (Gómez-Gil et al., 2012) and improved quality of life (van Leerdam et al., 2021; White Hughto & Reisner, 2016). However, the prevalence of severe depressive symptoms in the first years of GAHT is still relatively high: respectively, 23% and 26% of transgender persons experience significant symptoms of depression after 12 and 18 months of GAHT (Aldridge et al., 2021; Colizzi et al., 2014). Other studies find that masculinizing and feminizing hormones have different impacts on mood: Masculinizing GAHT could flatten positive and negative mood, whereas findings are mixed for effects of feminizing GAHT on mood (Matthys et al., 2021; Slabbekoorn et al., 2001; Wierckx et al., 2012). It is also possible that feminizing and masculinizing hormones have different effects on neurobiology. Use of masculinizing GAHT was associated with increased binding to serotonin reuptake transporter (SERT; Kranz et al., 2015), downregulation of monoamine oxidase A (MAO-A; Kranz et al., 2021), and changes in brain metabolites (Collet, Bhaduri, et al., 2023). Use of feminizing hormones was associated with decreased binding to SERT (Kranz et al., 2015), but no changes in downregulation of MAO-A (Kranz et al., 2021). It is possible that these changes could also result in in differing effects of masculinizing or feminizing GAHT on depressive symptoms.
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