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Introduction: Combined oral contraceptive (COC) use has been associated with stress-like, metabolic, and inflammatory alterations. Previous studies demonstrated that metabolic changes were related to cortisol. However, broad immune marker patterns in COC users remain insufficiently characterized, despite evidence of inflammatory involvement. This study investigates COC-related alterations in broad immune marker profiles and whether these are related to cortisol. Methods: Data from 392 premenopausal women (128 COC users) of the general population-based SHIP-TREND-0 cohort were analyzed using linear models to estimate differences between COC users and non-users. Immune markers included basic inflammation parameters and a broad panel of cytokines, growth factors, and chemokines. Indirect effects through cortisol were tested in structural equation models. Results: Compared to non-users, COC users had higher cortisol (β=1.24, p<0.001). Higher CRP (β=0.97, p<0.001), and vascular growth factors (i.e., PDGF-AB/BB and VEGF-A; both β=0.27, p<0.05) in COC users were related to cortisol (indirect effects: 0.21 to 0.30; all p<0.05). COC users had fewer monocytes (β=-0.52, p<0.001) and altered chemokine levels (i.e., lower eotaxin and higher MIG levels; β=-0.58 and 0.36, all p<0.001), for which no indirect effects were detected. Discussion: COC use was associated with broad immune profiling, representing one of the first broad immune marker assessments in COC users. Indirect effects through cortisol suggested both cortisol-dependent and cortisol-independent pathways. These findings provide novel evidence for systemic immunological correlates of COC use and highlight routes of association with endocrine regulation.
Klinger-König et al. (Mon,) studied this question.