A meta-analysis of cortisol response to challenge in human aging: importance of gender

Introduction: An increased cortisol response to challenge is associated with a variety of age-related disorders such as Alzheimer's disease, depression, diabetes, metabolic syndrome, and hypertension. Among the healthy elderly, an increased cortisol response to challenge may be a risk factor for developing these age-related disorders. Methods: We searched Pubmed, Embase, PsychInfo, Biosis, and Digital Dissertations (January 1966-June 2003) and included 45 parallel-group (young vs. old subjects) studies that used either a pharmacological or psychological challenge in healthy volunteers and measured cortisol response to challenge. We calculated effect sizes (Cohen's d) for the standardized mean differences between groups. Results: Compared to younger controls (n=670, mean age 28 years±5), older subjects (n=625, 69±6) showed a larger cortisol response to challenge defined as stronger response to stimulation or less inhibition after a suppression test (d=0.42, 95% confidence interval [CI], 0.26–0.57). The effect of age on cortisol release was significantly stronger in women (d=0.65, 95% CI 0.34–0.97) than men (d=0.24, 95% CI 0.02–0.47). Conclusions: Our results demonstrate that aging increases the cortisol response to challenge. This effect of age on cortisol response is almost three-fold stronger in women than men. Prospective studies should explore whether the higher cortisol response in the elderly is a risk factor for developing neuropsychiatric and medical disorders.