Association Between Hair Cortisol, Dehydroepiandrosterone and Perceived Stress in Chronic Stress-related Conditions: A Systematic Review and Meta-analysis.

BACKGROUND

Hair concentrations of cortisol and dehydroepiandrosterone (DHEA) are increasingly recognized as non-invasive, retrospective biomarkers of hypothalamic-pituitary-adrenal axis function. The ratio of these hormones may reflect the balance between catabolic and anabolic activity, potentially serving as a composite marker of chronic stress. Despite its theoretical relevance, the clinical utility of the hair cortisol: DHEA ratio remains unclear. This PROSPERO-registered systematic review, done according to PRISMA guidelines, aimed to evaluate the association between the hair cortisol: DHEA ratio and perceived stress in adults with chronic stress exposure.

METHODS

A comprehensive search of five electronic databases and grey literature was conducted up to March 5, 2025. Studies were eligible if they included adults (≥18 years) with at least 4 weeks of documented chronic stress exposure and reported both hair cortisol and DHEA concentrations alongside validated perceived stress measures. Meta-analyses were performed for correlation coefficients and group comparisons. Risk of bias was assessed using a modified Downs and Black checklist.

RESULTS

Eight studies (five cross-sectional, three cohort; = 60-210) met inclusion criteria. A meta-analysis of two studies using validated stress scales showed no significant association between the hair cortisol/DHEA ratio and perceived stress ( = 0.09; 95% CI: -0.07 to 0.26; ² = 0%). However, a separate analysis of three studies comparing high- versus low-stress groups revealed a moderate, statistically significant pooled effect (Hedges' = 0.69; 95% CI: 0.14-1.24; = .01) with substantial heterogeneity (² = 77.17%). Risk of bias ranged from moderate to low, but the overall certainty of evidence was rated very low due to small sample sizes and inconsistent findings.

CONCLUSION

The hair cortisol: DHEA ratio has biological plausibility as a marker of chronic stress, but current evidence is insufficient to support its clinical application. Further standardized, longitudinal studies are needed to establish its diagnostic and prognostic value.

PROSPERO REGISTRATION

CRD420251003364.