Chapter 1 20 no sex differences in the age of onset or rates of recurrence or chronicity (Rubinow & Schmidt, 2019). Sex hormones and depression during the lifespan Changes in female sex hormones could increase the risk of depression (Schiller et al., 2016). Epidemiological studies show an increased risk of depression during and after pregnancy, and it has been suggested that this is associated with the strong increase and drop in sex hormone levels during pregnancy and postpartum (Eisenlohr-Moul et al., 2023). Furthermore, sex hormones also show strong fluctuations in the perimenopause, which could also contribute to depressed mood (Joffe et al., 2020). Experimental hormone manipulation studies have further explored this hypothesis. Suppression of endogenous estrogen and progesterone production in healthy reproductive-age females resulted in increased depressive symptoms (Ben Dor et al., 2013; Frokjaer et al., 2015). Frokjær et al. (2015) also found an association between the magnitude of endogenous hormone changes and depression: participants showing stronger reductions in estradiol after hormone suppression also reported stronger increases in depressive symptoms. Other studies assessed effects of hormone suppression and add-back of exogenous hormones in supraphysiological doses: they find that in women with a history of postpartum depression, both hormone suppression and add-back of exogenous hormones had adverse effects on mood (Eisenlohr-Moul et al., 2023). Others have hypothesized that testosterone in men could be protective against depression, although studies on this topic are scarce. Hypogonadal men, who have clinically low testosterone levels, are more likely to report depressive symptoms (Hintikka et al., 2009). Men aged 60 or older are more likely to show clinically low testosterone (Kaufman & Vermeulen, 2005), but it is not clear whether this is also associated with clinically relevant symptoms, nor whether this requires hormonal treatment (Yeap et al., 2018). Research on the association between depression and testosterone levels in nonhypogonadal men is mostly inconclusive, with most studies finding no association between testosterone and depression (de Wit, Giltay, de Boer, Nolen, et al., 2021). Studies on the effect of testosterone treatment in depressed men show a possible favourable effect of testosterone treatment on depressive symptoms compared to placebo (Walther et al., 2019),
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