More pronounced diurnal cortisol rhythms are longitudinally associated with less fatigue in colorectal cancer survivors: A 12-month prospective cohort study.
Abstract
Background
Fatigue is amongst the most debilitating cancer-related symptoms, affecting up to one-third of colorectal cancer (CRC) survivors. Accumulating evidence implicates dysregulation of HPA axis as a potential mechanism contributing to chronic fatigue syndrome. We examined longitudinal associations between parameters of diurnal cortisol rhythms and fatigue in CRC survivors up to 12 months after treatment.
Methods
Seventy-four survivors of CRC were assessed at 6 weeks, 6 months and 12 months after treatment. At each point, salivary samples were collected five times per day over two consecutive days to measure cortisol concentrations. Relative amplitude (RA), diurnal slope, area under the curve (AUCg) and cortisol awakening response (CAR) were derived as a comprehensive assessment of diurnal cortisol rhythms. Fatigue was assessed at all time points using the Checklist Individual Strength (CIS; range overall score: 20-140; motivational subscale: 4-28) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC; range: 0-100). Longitudinal associations were analyzed using confounder-adjusted linear mixed models, with coefficients (β) indicating differences in fatigue scores over time per SD increase in cortisol parameters.
Results
A higher RA was associated with less overall fatigue (EORTC: β= -1.42; 95%CI: -2.82, -0.03; CIS: β= -1.82; 95%CI: -3.63, -0.01). A flatter diurnal slope, indicating less decline in cortisol over the day, was associated with more fatigue (EORTC: β=1.64; 0.25, 3.03) and increased motivational fatigue (CIS: β= 0.45; 0.02, 0.88).
Conclusion
More pronounced diurnal cortisol rhythms, specifically a higher RA and steeper diurnal slope, were longitudinally associated with less fatigue in CRC survivors. These findings may suggest that improving 24-h cortisol rhythmicity could be a target for interventions to reduce fatigue in CRC survivors, but this warrants further investigations.