8291039 Circadian Disruption of Steroid Hormone Rhythms in Night Shift Workers: Findings from the EPHOR-NIGHT Study

<h3>Objective</h3> Night shift work affects circadian rhythms, yet its influence on the rhythmicity of steroid hormones remains insufficiently characterized in large epidemiological studies. We examined the association between night shift work and the diurnal patterns of melatonin and steroid hormone metabolites using cosinor analysis in the EPHOR-NIGHT multicenter European cohort. <h3>Material and Methods</h3> We included 590 workers (336 night shift and 254 day workers) from Spain, Sweden and Denmark. Participants reporting use of melatonin supplements were excluded. Participants provided repeated saliva samples (n=5) over the course of one day, enabling the characterization of circadian rhythms for melatonin and steroid hormone metabolites. Cosinor models were fitted to estimate individual mesor (rhythm-adjusted mean) and acrophase (timing of peak), and associations with night shift work compared to permanent day work were evaluated using geometric mean ratios (GMRs) and differences (GMDs), adjusting for age, sex, educational level, season, and study center. <h3>Results</h3> Night shift work was associated with marked delays in acrophase for all hormones studied. Melatonin showed a 2.5-hour delayed peak (GMD: 2.46 hours; 95% CI: 1.36–3.56), while cortisol and several of its metabolites—including 20α- and 20β-dihydrocortisol, and 5α-tetrahydrocortisol—exhibited peak delays of approximately 3.2 to 3.9 hours (all p&lt;0.001). Additionally, night shift workers demonstrated lower mesor levels for all metabolites examined but only significant for cortisol (GMR: 0.81; 95% CI: 0.70–0.95), 20α-dihydrocortisol (GMR: 0.83; 95% CI: 0.74–0.94), and 5α-tetrahydrocortisol (GMR: 0.84; 95% CI: 0.72–0.97), indicating a reduction in overall hormone production. <h3>Conclusion</h3> We observed that night shift work is associated with both a delayed circadian phase and reduced mean levels of melatonin and cortisol-related metabolites. These results support the hypothesis that circadian misalignment in shift workers leads to systemic hormonal disruption, potentially contributing to long-term health risks associated with shift work. <h3>Funding</h3> Horizon2020 (874703) and FIS (PI22/01683).