Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol

Abstract

Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.

Flattening the Glucocorticoid Rhythm causes Changes in Hippocampal Expression of Messenger RNAs Coding Structural and Functional Proteins: Implications for Aging and Depression

“…In the present study, we used a manipulation that produces glucocorticoid levels that are clamped at the midpoint of the diurnal rhythm and hence are increased at the nadir but decreased at the zenith relative to the normal rhythm. The corticosterone profile generated is very similar to that seen in aged rats (Hauger et al, 1994) and similar to the profile of cortisol levels in aged human subjects (Deuschle et al, 1997a;Ferrari et al, 2001;Van Cauter et al, 1996;Wong et al, 2000). The elevated nadir and flattened rhythm is also consistent with the pattern observed in depressed patients, although in this group the peak of the diurnal rhythm is preserved, or even marginally elevated, resulting in an increase in 24 h cortisol exposure (Deuschle et al, 1997b;Wong et al, 2000).…”

“…However, more subtle changes in glucocorticoid levels are comparatively prevalent, and furthermore often go untreated. Thus in the normal aging process, there is a significant flattening of the normal diurnal rhythm of cortisol secretion (Ferrari et al, 2001;Van Cauter et al, 1996;Deuschle et al, 1997a). In addition, several common psychiatric disorders including affective disorders, cortisol secretion is moderately increased and there is a marked flattening of the diurnal rhythm (Deuschle et al, 1997b;Ferrari et al, 2001).…”

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

“…Many studies have found an inverse relation between delta sleep and pulsatile cortisol release (see Vgontzas et al, 1999;Born et al, 1991 for a review). Normal aging is associated with a concurrent rise in secretory HPA activity and a reduction in delta sleep (Dodt et al, 1994;Feinberg et al, 1967;Gillin et al, 1981;Van Cauter et al, 1996). Aging is also associated with increased cortisol response and more decreases in delta sleep in response to mild laboratory stressors (Prinz et al, 2000).…”

Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder

“…Many studies have found an age-associated increase in HPA activity (Van Cauter et al, 1996), resulting in elevated cortisol levels (Lupien et al, 1994;Ferrari et al, 1995;Deuschle et al, 1997) and attenuation, or a flattening, of cortisol diurnal rhythm (van Coevorden et al, 1991) suggesting age-dependent HPA axis dysregulation. Additionally, it has long been speculated that chronic elevations of stress-related hormones such as cortisol can weaken multiple physiological systems of older adults resulting in impaired cardiovascular and immune function, as well as contributing to dementia, and mood and anxiety disorders.…”