Chapter 4 106 levels transiently increase and peaks typically within 30 minutes after awakening to return to baseline levels about 60 minutes after awakening. The dynamic phenomenon is called the cortisol awakening response (CAR), and it can be measured by serial saliva home-sampling from 0 to 60 minutes after awakening. The CAR appears to be more prominent in women than men (Wüst et al., 2000). This sex difference could be related to sex hormone effects, since sex hormones have been shown to affect circadian and dynamic changes in the HPA axis (Handa et al., 1994). This theory is further supported by observations in OC users, in whom a lower CAR has been detected compared to naturally cycling (NC) women (Bouma et al., 2009; Høgsted et al., 2021). Researchers have hypothesized that the synthetic estrogens and progestins in OCs, which suppress the gonadal hormone axis, could blunt the HPA axis reactivity and reduce CAR magnitude (Hertel et al., 2017). It is possible that these changes in HPA axis dynamics could affect sleep quality, but this is not yet clear. Zhang et al. (2014) found that absolute cortisol levels after awakening showed opposing associations with insomnia in a sex-specific manner: men with insomnia showed lower absolute cortisol levels at 30, 60 and 90 minutes after awakening compared to men without insomnia, whereas women with insomnia showed higher absolute cortisol levels after awakening compared to women without insomnia. This finding suggests a possible sex disparity in the association between insomnia and cortisol levels after awakening. However, these findings have not been replicated, and Zhang et al. only compared absolute cortisol values instead of the cortisol awakening response, which captures the cortisol dynamics less well. Furthermore, the study did not account for hormonal contraceptive use in the female participants. In this preregistered study we examine overall sleep quality, and in particular sleep disruptions, and the relationship between these and CAR in OC users, NC women and men. We firstly aim to replicate and possibly crossvalidate the insomnia finding from Morssinkhof et al. (2021), evaluating differences in sleep quality and sleep disruptions in healthy OC users compared to healthy naturally cycling (NC) women. We also aimed to expand these findings by comparing NC women to men. Secondly, we aim to
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