Sex Differences in Basal Cortisol Levels Across Body Fluid Compartments in a Cross-sectional Study of Healthy Adults

Abstract

Context: Many studies have moved toward saliva and peripheral blood sampling for studying cortisol, even in relation to disorders of the brain. However, the degree to which peripheral cortisol reflects central cortisol levels has yet to be comprehensively described. Data describing the effect that biological characteristics such as age and sex have on cortisol levels across compartments is also limited. Objective: To assess the relationships of cortisol levels across cerebrospinal fluid (CSF), saliva, and plasma (total and free) compartments and describe the effects of age and sex on these relationships. Design: Multisite cross-sectional observation study. Setting: Samples collected in academic outpatient settings in 2001-2004. Patients or other participants: Healthy community volunteers (n = 157) of both sexes, aged 20-85 years. Interventions: None. Main outcome measures: This study was a secondary analysis of data collected from a previously published study. Results: CSF cortisol correlated more strongly with plasma (r = 0.49, P < .0001) than with saliva cortisol levels. Sex but not age was a significant modifier of these relationships. CSF cortisol levels trended higher with older age in men (R2 = 0.31, P < .001) but not women. Age-related cortisol binding globulin trends differed by sex but did not correlate with sex differences in cortisol levels in any compartment. Conclusion: Variability in the correlations between central and peripheral cortisol discourages the use of peripheral cortisol as a direct surrogate for central cortisol measures. Further investigation of how mechanistic drivers interact with biological factors such as sex will be necessary to fully understand the dynamics of cortisol regulation across fluid compartments.