BackgroundIt has been hypothesized that stressful life events are associated with changes in hypothalamic–pituitary–adrenal (HPA) axis regulation, which increases susceptibility to psychiatric disorders. We investigated the association of early and late life events with HPA axis regulation in older persons.MethodWithin the Longitudinal Aging Study Amsterdam (LASA) 1055 participants (47% male), aged 63–93 years, collected saliva within 30 min after waking and late in the evening. Early and late life events were assessed during a home interview. The associations between life events and cortisol levels were examined using linear regression and analysis of covariance with adjustments for demographics, cardiovascular risk factors and depressive symptoms.ResultsWithin our sample, the median morning and evening cortisol levels were 15.0 nmol/l [interdecile range (10–90%): 7.4–27.0 nmol/l] and 2.8 nmol/l (10–90%: 1.5–6.3 nmol/l), respectively. Persons who reported early life events showed lower levels of natural log-transformed morning cortisol [B=−0.10, 95% confidence interval (CI) −0.17 to −0.04] and flattened diurnal variability of cortisol (B=−1.06, 95% CI −2.05 to −0.08). Those reporting two or more late life events showed higher levels of natural log-transformed morning cortisol (B=0.10, 95% CI 0.02–0.18) and higher diurnal variability (B=1.19, 95% CI 0.05–2.33). No associations were found with evening cortisol.ConclusionsThe results of this large population-based study of older persons suggest a differential association of early and late life events with HPA axis regulation; early life events were associated with a relative hypo-secretion of morning cortisol and flattened diurnal variability, while late life events were associated with elevated secretion of morning cortisol and high diurnal variability of cortisol.