Background: The striking link between Cushing syndrome, the metabolic syndrome (MetS), and cardiovascular disease suggests that long-term exposure to high glucocorticoid levels catalyzes cardiometabolic deterioration. However, the relation of subtle variations in long-term glucocorticoid levels with MetS remains poorly understood. Specifically, little is known about potential moderating roles of age, sex, and mental health status in this association.
Design: We investigated the association of long-term glucocorticoid levels with MetS using data of 1405 participants (73.4% women) of the Netherlands Study of Depression and Anxiety. Predictors included hair cortisol and cortisone levels. Outcomes were MetS presence, number of MetS components, and individual component (ie, diastolic blood pressure, waist circumference, and fasting glucose, high-density lipoprotein cholesterol, and triglycerides). We investigated potential interactions with age, sex, and mental health status.
Results: Hair glucocorticoid levels were positively associated with MetS presence (OR = 1.27; 95% CI = 1.11-1.44, and OR = 1.32; 95% CI = 1.14-1.52 for hair cortisol and cortisone, respectively), number of MetS components, waist circumference, and triglyceride levels. Hair cortisol, but not cortisone, was in trend associated with diastolic blood pressure and high-density lipoprotein cholesterol levels. No associations were seen with blood glucose. Of note, the relationship of hair cortisone with MetS was stronger among younger compared to older individuals (OR = 1.95; 95% CI = 1.50-2.54 vs OR = 1.14; 95% CI = .96-1.35 in younger vs older participants).
Conclusion: Long-term biological stress, measured through hair glucocorticoid levels, is associated with MetS presence, especially among younger individuals. Prospective studies need to evaluate the extent to which hair cortisol and cortisone add to standard risk factors when predicting future cardiometabolic diseases.
Keywords: HPA-axis; age; cardiovascular risk factors; cortisone; hair glucocorticoids; metabolic syndrome.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.