General introduction 11 1. General introduction 1.1. Sex differences in mental health in history Long before modern psychiatric classifications, healthcare providers believed that their patients’ sex could affect their mental health. Physicians from the ancient Egyptian and Greek societies believed that in females, the uterus could make “spontaneous, wandering movements” through the body. This could result in anxiety and nervousness, insomnia, low mood, irritability and a wide range of somatic symptoms. The Greek physician Hippocrates called this syndrome “hysteria”, named after the Greek word for uterus (Trimble & Reynolds, 2016), which was possibly the first sex-specific diagnosis in psychiatry. Although its meaning changed over the course of history, diagnoses of hysteria were most prevalent in women, and they were a commonplace occurrence up until the first half of the 20th century. The use of “hysteria” as a diagnostic term declined, and in 1980 references to hysteria were removed from psychiatric handbooks (Tasca et al., 2012). However, sex differences still exist in the prevalence of psychiatric illnesses: women are two times more likely to experience depression and 1.5 times more likely to experience insomnia compared to men (Kessler, 2003; Zhang & Wing, 2006). Although these prevalence differences have been attributed to social and psychological factors, researchers hypothesize that biological factors also contribute to higher prevalence of depression and insomnia (Altemus et al., 2014; Suh et al., 2018). One of the biological factors that gained more research attention is the role of sex hormones (SchweizerSchubert et al., 2021). There is an increased risk of mood disorders and insomnia in the female lifespan during times when sex hormones fluctuate. This is seen around pregnancy and in the peri-menopause: 10 to 15% of pregnant people experience peripartum depression, and risk of depression doubles in perimenopause (de Kruif et al., 2016; Shorey et al., 2018). Furthermore, 3 to 18% of women report depressive moods associated with their menstrual cycle (Halbreich et al., 2003). The presence of significant sex differences in the prevalence of depression and insomnia, and the increased risk of both disorders in life phases when hormones strongly change have raised questions on the possible role of sex hormones: could sex hormones actually be a contributing factor for these conditions?
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