Influence of sex hormone use on sleep architecture in a transgender cohort 167 1. Introduction There are many known physiological differences between men and women, but one of the lesser known sex differences is found in sleep architecture. Sleep architecture, which can be measured with sleep electroencephalography (EEG), refers to the organization of sleep into sleep depth and sleep stages. When measuring sleep with EEG, healthy women generally show better sleep quality than healthy men (e.g. longer total sleep time, less time awake during the night, longer deep sleep and longer REM latency; Bixler et al., 2009; Roehrs et al., 2006). Although researchers have intensively studied sleep architecture and the underlying neural mechanisms, the cause of these sex differences in sleep architecture is still not fully understood. One of the hypothesized mechanisms underlying the sex differences in sleep architecture is attributed to the effect of sex hormones. In mice, sex differences in sleep architecture are eliminated after gonadectomy, which results in the loss of sex steroid production (Paul et al., 2006). Female mice also show longer REM sleep durations after gonadectomy, and restoration of estradiol levels through supplementation also restores the shorter REM sleep duration (Cusmano et al., 2014; Deurveilher et al., 2011). There are indications that the influence of sex steroids is sex-specific: an experiment using administration of estrogen and testosterone in female and male rats shows that female, but not male, rats show changes in sleep (e.g. increased wakefulness, changes in REM sleep) after administration of either hormone (Cusmano et al., 2014). In humans, knowledge on exogenous sex hormones and sleep architecture in participants without hormonal disorders is still scarce. Studies have mainly focused on clinical groups using hormone therapy, such as women during the perimenopause and hypogonadal men. A few studies in healthy reproductive-age persons showed indications of sex hormone effects on sleep architecture. In healthy men with induced hypogonadism, testosterone supplementation resulted in more deep sleep and a longer REM sleep latency compared to placebo (Leibenluft et al., 1997). Similarly, estrogen therapy in hypogonadal females resulted in decreased sleep onset latency and longer REM sleep duration compared to placebo (Schiff, 1979). Findings on progesterone are less consistent: Progesterone administration was found to have a sedative effect in healthy males and females
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