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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. 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. 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 …