Association between hair cortisol concentration and cancer-related outcomes in adult patients: A systematic review.

BACKGROUND: Chronic stress, through sustained hypothalamic-pituitary-adrenal (HPA) axis activation, has been implicated in cancer progression. Hair cortisol concentration (HCC) offers a unique retrospective window into cumulative cortisol exposure, yet its relationship with cancer outcomes has never been systematically examined. OBJECTIVE: To critically appraise the evidence linking HCC to cancer-related outcomes in adults and to identify the methodological gaps that currently limit this emerging field. METHODS: Four databases (PubMed, Embase, Scopus, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched from inception to March 2026. Adults with confirmed cancer and HCC measured by any validated method were eligible. Risk of bias was assessed using Cochrane RoB 2, the Newcastle-Ottawa Scale, and the JBI checklist according to study design. Narrative synthesis followed SWiM guidelines. PROSPERO registration: CRD420261328214. RESULTS: From 2313 initial records, six studies (two randomised trials, two cohorts, two cross-sectional) met the inclusion criteria, spanning seven countries with 6683 participants. Elevated HCC predicted shorter disease-free and overall survival following curative hepatocellular carcinoma treatment. Hair cortisone, but not cortisol, was associated with cancer incidence in a population-based cohort after adjustment for age and gender. Breast cancer survivors showed significantly higher HCC than matched controls. One intervention trial demonstrated a significant reduction in HCC following a psychosocial programme, while another found no effect. Reported HCC varied widely across studies, with LC-MS/MS-based measurements ranging from below 3 to approximately 60 pg/mg, while a single ELISA-based study reported a mean of 1751 pg/mg, a discrepancy largely driven by analytical platform differences. Methodological quality was variable, with confounder adjustment and missing biological data representing recurring concerns. CONCLUSIONS: Limited evidence suggests that elevated chronic cortisol exposure may be associated with adverse survival outcomes in patients with established malignancies, while findings regarding cancer incidence remain inconclusive. Analytical heterogeneity, limited confounder control, and the predominance of breast cancer studies constrain the strength of these conclusions. Standardised measurement protocols and prospective longitudinal designs are essential next steps.