Associations between sex hormones, sleep problems and depression 237 Thus, for understanding the interaction between sleep, sex hormones and mood, the studies that investigated differences between women with PMDD and healthy controls, and the women with low or high endogenous progesterone were useful. Women with more depressive symptoms through PMDD showed altered sleep despite similar endogenous hormone levels, and women with lower progesterone levels had a stronger increase in negative mood if their REM sleep timing changed more throughout their cycle. 4. Discussion 4.1. Summary This systematic review summarizes and compares studies that examine sex hormones, sleep problems and depressive symptoms or a diagnosis of depression. It shows that previous studies mainly investigated the influence of endogenous female gonadal sex hormones, with most studies exploring effects of endogenous short-term fluctuations (in the form of menstrual cycle monitoring) (n=5), and only a few studies exploring effects of long-term hormone changes (e.g. prospective female ageing studies over a number of years) (n=3). Studies in males are lacking (n=1), and no studies assessed the effect of administered testosterone. Moreover, controlled pre-post studies assessing the influence of sex hormone interventions are sparse (n=2). Synthesis of the results of this systematic review firstly replicates the assumed bidirectional relationship between sleep and depression, showing that depressed patients have prolonged sleep latency and more subjective sleep problems. Additionally, an increase in sleep problems can result in - or accompany an increase of - depressive symptoms or a diagnosis of depression. Secondly, the evidence for a direct relationship between endogenous sex hormone levels and sleep seems to be stronger than the evidence for a relationship between endogenous sex hormone levels and depressive symptoms. Higher estrogen levels may be protective against reported sleep problems, a relationship between endogenous hormone levels and depression was inconclusive. In the studies that used a hormone intervention, all three interventions did show an effect on sleep and mood.
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