Does hair cortisol concentration reflect measurable regulatory biology of the HPA axis in healthy humans?

Salivary cortisol measures and hair cortisol concentration (HCC) have been extensively used in epidemiological work to document links between stress biology and health. Though their value as stress biomarkers is well-established, little prior work grounds these field-friendly cortisol measures in the hypothalamic-pituitary-adrenal (HPA) axis regulatory biology that likely provides the mechanistic pathways connecting stress and health. Understanding mechanisms may facilitate intervention and disease prevention. Our prior work linked salivary cortisol measures to adrenal sensitivity and to glucocorticoid-mediated feedback inhibition. Here we utilized a subset of this healthy convenience sample (n = 117) to link HCC to laboratory probes of HPA axis regulatory biology. Over the course of a month, subjects participated in 5 regulatory tests: ACTH stimulation, dexamethasone/CRH test, metyrapone, dexamethasone suppression (DST), and Trier Social Stress Test. They provided hair samples at the beginning and end of that month and six days of saliva samples during it. All-subsets regressions were used to link hair cortisol to regulation. The best model explained 23 % of the variance in HCC (current and past month) using feedback sensitivity (8.7 %), adrenal sensitivity 8 %), and stress reactivity (5.3 %). These associational analyses require formal hypothesis testing in independent samples for confirmation; but adrenal sensitivity and feedback inhibition likely warrant more study as mediators of and perhaps mechanistic contributors to stress-health links demonstrated epidemiologically with HCC. Identifying ways to directly assess them in stress field work may have value. Future studies should also measure hair washing frequency (additional 19 % of variance explained) and recognize that HCC is not a simple way to quantify stress exposure or stress sensitivity.