Chapter 8 220 sleep in sleep-deprived mice. Importantly, testosterone can also be metabolized into substances that act like agonistic GABA-A receptor modulators, as seen in progesterone metabolites (Edinger & Frye, 2004), and it can be aromatized into estradiol, thus affecting estrogen receptors (Frye et al., 2008). Thus, there can be overlap between effects of testosterone, progesterone and estrogen. 1.3. Aims of current systematic review There is no recent overview on the relationship between sex hormones, sleep and depressive symptoms. In 1999, Manber & Armitage published an insightful narrative review on the association between sex hormones, sleep and depressive problems. Since then, new studies have been conducted on this topic and new methods have been used, such as the more reliable liquid chromatography–mass spectrometry (LC-MS) for hormone measurements and advanced ambulant monitoring methods for sleep. This systematic review of more recent studies, including these methods, can provide new insights in the relation between sex hormones, sleep and depressive symptoms. In this review, we aim to provide an overview of peer-reviewed studies that investigated sex hormones, either via endogenous sex hormone level measurements or interventions via exogenous hormones (Intervention/ Indicator and Control) in healthy reproductive-age adults (Population and Control) and subjective and objective sleep and diagnosis of depression and/or depressive symptoms (Outcome), in retrospective, prospective and cross-sectional studies, with either an observational or interventional design (Study designs). These findings could provide insight into whether sex hormones influence sleep problems and depressive symptoms. 2. Methods A review protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement (www.prismastatement.org) (Moher et al., 2009) and was submitted to Prospero under review number CRD42019125970.
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