General discussion 263 after awakening (Høgsted et al., 2021; Chapter 4 in this thesis) and after stress tasks (Barel et al., 2018; Merz, 2017). These findings are partially illustrated in Figure 9.1. Recent work also shows that these effects could be dependent on OC formulations (Herrera et al., 2019), with the second generation progestins (i.e., those containing levonorgestrel and norgestrel) possibly having a larger effect on cortisol responses compared to other formulations. The findings in Chapter 4 of this thesis show that there could be OC-specific associations between disrupted and the cortisol awakening response. Although studies in humans examining the effects of OCs on both mood and cortisol are still scarce, recent work in mice showed that administration of ethinylestradiol and levonorgestrel, but not administration of ethinylestradiol and drospirenone, reduced stress-induced cortisol responses and increased anhedonia-like behaviours (Schuh et al., 2024). Based on this work, changes in the HPA axis could be one of the underlying mechanisms in OC-associated low mood. Research on GAHT and cortisol dynamics is more limited. Fuss et al. (2019) tested the effects of GAHT on HPA axis responsivity by using a Dex/CRH test, meaning they pharmacologically suppressed and then stimulated the HPA axis. They found that after 3 months of feminizing GAHT, participants showed increased ACTH and cortisol production in response to CRH administration, whereas after 3 months of masculinizing GAHT, participants showed decreased ACTH and cortisol production in response to CRH administration; these findings are also illustrated in Figure 1. These findings implicate that estradiol and anti-androgens could increase HPA axis responsivity, whereas testosterone could reduce this response. Social factors could also affect HPA axis activity in transgender people: perceived stress and transgender-specific stressors were also shown to affect diurnal cortisol in transgender persons (Colizzi et al., 2013; DuBois et al., 2017).
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