Waves of Change: Sex Hormones, Depression and Sleep

Depression is twice as common in women compared to men, and the risk of insomnia is 1.5 times higher in women than in men during the reproductive age. It has been suggested that sex hormones, including estrogen, testosterone and progesterone, may partly explain this difference in prevalence. Changes in these hormones may possibly contribute to more depressive symptoms and more insomnia. One way to examine the effects of sex hormones on depression and sleep is to investigate situations where individuals start taking exogenous hormonal medications. Therefore, this study aimed to examine the effects of oral contraceptives (OCs) and the effects of gender-affirming hormone therapy (GAHT). We examined whether the use of OCs and GAHT affected depressive symptoms, sleep quality, sleep architecture and chronotype. The main research questions in this thesis were: 1. Are OC use and GAHT use associated with changes in depression? 2. Are OC use and GAHT use associated with changes in sleep? 3. What are the effects of sex hormones on the association between depression and sleep? 1. Sex hormones and depression Our findings show that OC use could be associated with increases in depressive symptoms and increased risk of depression, but that there might be strong individual differences in the effects of OCs on mood. Our findings in transgender people who start GAHT suggest that masculinizing and feminizing sex hormones have different effects on depressive symptoms, although it must be noted that we find only small to modest changes. 2. Sex hormones and sleep We find that use of OCs could possibly have very small effects on sleep, and that this could be related to the day-night rhythm of the hormone cortisol. In our studies on GAHT, we see that transgender people on masculinizing GAHT show no clinically significant changes in insomnia or sleep quality, but they show shorter slow wave (deep) sleep and slightly longer and earlier REM (dream) sleep after starting GAHT, as well as a later chronotype. After starting feminizing GAHT, transgender people show a shorter subjective sleep onset latency, no changes in sleep architecture and an earlier chronotype. 3. Sex hormones, depression and sleep Results from our systematic review and our studies on OCs and GAHT do not provide substantive support for the hypothesis that sex hormones affect the relationship between depression and sleep. The research results in this thesis show that changes in sex hormones can lead to small changes in depressive symptoms that are in line with prevalence differences in the population: feminizing hormones, including OAC and GAHT, can lead to modest increases in depressive symptoms and masculinizing GAHT can lead to modest decreases in depression symptoms. The effects of sex hormones on subjective sleep vary, and GAHT was found to have strongest effects on sleep architecture and chronotype. The hypothesis that sex hormones cause poor sleep, which would then lead to increases in depressive symptoms, was not supported by our findings. For future studies on mood, I emphasize the importance of examining short-term changes in mood, since changes in daily moods and mood variability have been described after sex hormone changes. For future studies on sleep, I recommend to further study the role of previous and current sex hormone status (i.e., OC use, menopause status) on sleep architecture and chronotype. Lastly, I advocate for the inclusion of sex and sex hormones in psychiatric research and in clinical practice, to provide knowledge and techniques for prevention, early detection and treatment of sex hormone-related problems in sleep and mood.