General discussion 279 insights into the role of sex hormones in chronotype, future studies should explore shifts in chronotype in those who use hormonal therapies. 4.2. Sex hormones: taking a lifespan approach Female sex hormones, and especially sex hormone changes, could pose a possible risk for mental health throughout the lifespan. Findings in this thesis show that the use of estrogens or progestins can contribute to lower mood or depressive symptoms, and some individuals might be more sensitive to this effect than others. The risk of depressive symptoms after the use of exogenous sex hormones, such as OCs or feminizing GAHT, is partially in line with observations in changes in endogenous sex hormones, as some also experience clinically relevant depressive symptoms in the premenstrual phase of the menstrual cycle, during or after pregnancy or during menopause. Although sex hormones could affect depression in both sexes, the generalization of these effects could be more relevant in women, since they experience stronger sex hormone fluctuations in the healthy lifespan. Most women menstruate and experience perimenopause and menopause, and many experience pregnancy and hormonal contraceptive use, which are all marked by significant sex hormone fluctuations. In contrast, men experience significantly smaller hormone fluctuations: they experience day-to-day diurnal fluctuations in testosterone but the amplitude of these hormone changes is lower than in women. This sex difference is also reflected in the prevalence of clinically relevant mental health problems during hormone fluctuations. An estimated 3 to 18% of women experience premenstrual dysphoric disorder (Halbreich et al., 2003), 10 to 15% experience postpartum depression (Shorey et al., 2018) and the risk of depression is at least 2 times higher during the perimenopause, and as much as 5 times higher in those who have a lifetime history of depression (de Kruif et al., 2016; Freeman, 2010). A hypothesis that has been studied in recent years is the idea that some women might be more sensitive to the effect of sex hormone fluctuations than others: this is also called the “hormonal sensitivity” hypothesis (as reviewed in Pope et al., 2017; Soares & Zitek, 2008). Numerous studies have tried to identify “hormone sensitive" participants, in order to better predict who is at risk of hormone-related mood complaints. This has been done
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