General introduction 17 Oral contraceptives Oral contraceptives (OCs) are the most commonly used form of hormonal contraceptives: worldwide, an estimated 151 million women use OCs (Haakenstad et al., 2022), with the majority using combined oral contraceptives, which consist of a combination of progestins and estrogens. Although intended use of OCs is for contraceptive purposes, it is also commonly used for non-contraceptive purposes, to regulate menstruation timing or to manage symptoms of gynaecological conditions. Although use of OCs has local effects on the uterus and ovaries, they also have systemic effects. The most well-studied risk resulting from these systemic effects are a slight increase in risk of breast cancer and thrombosis, but other possible side effects include weight gain, headaches, breast tenderness and possible mood changes (Burkman, 2001). Other possible systemic effects of OCs include changes in cortisol dynamics, with studies indicating that OC users show higher cortisol levels at rest (Boisseau et al., 2013), reduced cortisol responses to after awakening or stress (Høgsted et al., 2021; Nielsen et al., 2013) and chronic increased glucocorticoid signalling (Hertel et al., 2017). Despite increasing insights in these effects of OCs, it is yet unknown how some systemic effects, including changes in cortisol dynamics, relate to OC-associated side effects. It is estimated that more than 50% of OC starters discontinue OC use within 6 to 12 months, with 27% of OC starters reporting mood changes and 38% of starters reporting side effects as one of the most frequent reasons for discontinuation (Hall et al., 2012, 2014; Westhoff et al., 2007). Recent statistics show that the use of OCs is decreasing in youth, with user rates declining from 76% in 2012 to 46% in 2023 in youth aged 13 to 24 (De Graaf et al., 2023). In this group, reported side effects were one of the three most common reasons not to use OCs. Gender-affirming hormone therapy Gender-affirming hormone therapy (GAHT) is used by transgender persons, whose gender identity is not in line with their sex assigned at birth. GAHT can change their physical characteristics to be more in line with their gender identity. Transgender people commonly experiences gender dysphoria, which is the experience that one’s body is not in line with the gender that they identify with.
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