Chapter 9 272 3.2. Cross-sectional and longitudinal comparisons It is generally acknowledged that changes in sex hormones in relationship to well-being are best studied prospectively, assessing within-person changes (Schmalenberger et al., 2021), since cross-sectional studies assessing the effects of OCs or GAHT are most likely unable to fully control for population differences. In the case of OC use, the presence of healthy user bias would imply that the OC users who experience less OC-related side effects are more likely to be in the long-term user sample, resulting in an underrepresentation of OC users with side effects: this bias is also illustrated in Figure 9.4. The studies that examined OC use in this thesis have used a retrospective within- and between participant approach in Chapter 2 and a crosssectional approach in Chapter 4. In Chapter 2, we retrospectively compared depression prevalence and symptoms of depression and insomnia during either OC use or naturally cycling measurements. Although the main analyses in this paper did not show any significant differences between the two measurement groups, the longitudinal setup of the NESDA cohort enabled us to conduct between- and within-person analyses. These analyses revealed two opposing findings within the same cohort: participants who used OCs more often during the study period showed less depressive symptoms and a lower risk of mood disorders during OC use, whereas within-person comparisons show that participants who started or stopped OC use reported more severe depressive symptoms and higher risk of mood disorders during OC use. In these findings, we could hypothesize that the between-person comparison is affected by healthy user bias: participants who used OCs less often could be doing so due to experiencing side effects, as shown in figure 4. In Chapter 4, we assessed cross-sectional differences between OC users, naturally cycling women and men. There could be a healthy user bias in this study, meaning negative effects of OCs could have been underestimated.
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