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.