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.
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Only two studies of 143 and 177 healthy men and women aged 20 to 80 years have documented high fidelity sampling of circulating cortisol patterns across an entire 24-h day.
“Only two such studies, of 143 and 177 healthy men and women aged 20 to 80 years, respectively, are available [65, 66].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [66]
The Abstract (page not given) reports 177 cortisol profiles from normal men and women aged 18–83, supporting the study’s identification and approximate age range. The Subjects section (page not given) specifies that only 163 had 24-hour profiles; the other 14 were sampled for 8–10 hours overnight. Thus, the cited paper does not support the claim that all 177 had sampling across an entire 24-hour day. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPremenopausal women, but not older women, had lower 24-h and morning cortisol concentrations compared with age-matched men.
“Premenopausal women, but not older women, had lower 24-h, and morning, cortisol concentrations compared with age-matched men [65, 66].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [66]
24-h cortisol concentrations were independent of age in one study, but increased with age in the other.
“In contrast to the consistent findings previously outlined, 24-h cortisol concentrations were independent of age in one study [65], but increased with age in the other [66], for reasons that are not entirely apparent.”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [66]
Men above 30 years old were excluded to control for the impact of age on circadian rhythmicity of plasma cortisol.
“Men above 30 years old were excluded to control for the impact of age on circadian rhythmicity of plasma cortisol (Van Cauter et al., 1996).”
From The effects of exercise intensity on the cortisol response to a subsequent acute psychosocial stressor. (2021) · cites this paper as Van Cauter et al., 1996
Age is associated with higher late-afternoon and early-evening cortisol, and an advance in the timing of the cortisol rhythm, but not with cortisol-binding protein.
“These [65, 66] and other [67] studies are consistent in showing that age is associated with higher late-afternoon and early-evening cortisol, and an advance in the timing (i.e. phase) of the cortisol rhythm, but not with cortisol-binding protein [68].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [66]
The citation [68] is attached specifically to the claim that age is not associated with cortisol-binding protein. The Results and Discussion passages address age-related cortisol levels and rhythm timing, but no passage found addresses cortisol-binding protein or corticosteroid-binding globulin (searched both terms). (LLM, conf=0.74)
Experimental — accuracy not yet measured
The timing of the nadir and of the onset of the nocturnal cortisol rise are advanced in older adults of both sexes, and the circadian amplitude, when expressed as a percentage of the 24-hour mean level, is decreased.
“In addition, the timing of the nadir and of the onset of the nocturnal cortisol rise are advanced in older adults of both sexes and the circadian amplitude, when expressed as a percentage of the 24-hour mean level, is decreased”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [31]
Aging is associated, in both sexes, with a progressive increase of 24-hour mean cortisol levels from the 2nd to the 8th decade, a shorter quiescent period, and higher nadir values.
“In the same study, aging was associated, in both sexes, with a progressive increase of 24-hour mean levels from the 2nd to the 8th decade, associated with a shorter quiescent period and higher nadir values.”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [31]
In young adulthood, women have lower 24-hour mean cortisol levels, a longer quiescent period, a lower acrophase, and a lower absolute amplitude of the circadian variation compared to men.
“In young adulthood, women appeared to have, compared to men, lower 24-hour mean cortisol levels, a longer quiescent period (that started earlier and ended later), a lower acrophase, and a lower absolute amplitude of the circadian variation.”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [31]
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Relationships between cortisol level, mortality and chronic diseases in older persons
Schoorlemmer, R. M. M., Peeters, G. M. E. E., van Schoor, N. M., & Lips, P. T. A. M. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03552.x · Cited by 129 · see citing works
Diurnal cycles of salivary cortisol in older adults.
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The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity
Lockett, J., Inder, W. J., & Clifton, V. L. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae008 · Cited by 135 · see citing works
Heuser, I., & Lammers, C. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00048-4 · Cited by 126 · see citing works
Sexy thoughts: Effects of sexual cognitions on testosterone, cortisol, and arousal in women
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Acute effects of hydrocortisone on the human brain: An fMRI study
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Alterations of Circadian Rhythmicity and Sleep in Aging: Endocrine Consequences
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Self-citationAnxiety disorders and salivary cortisol levels in older adults: a population-based study
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Assessing individual systemic stress through cortisol analysis of archaeological hair
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Urinary cortisol excretion as a predictor of incident cognitive impairment
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Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm
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Purnell, J. Q., Kahn, S. E., Samuels, M. H., Brandon, D., Loriaux, D. L., & Brunzell, J. D. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90769.2008 · Cited by 112 · see citing works
- Authors
- Van Cauter, E.
- Venue
- Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1996-07-01
- Volume
- 81
- Issue
- 7
- Pages
- 2468-2473
- ISSN
- 0021-972X (ISSN-L)
- OpenAlex
- W2128979836
- Cited by
- 951
- References
- 0
- Citations by year
- 2026: 2 · 2025: 22 · 2024: 28 · 2023: 25 · 2022: 28 · 2021: 41 · 2020: 34 · 2019: 40 · 2018: 35 · 2017: 36 · 2016: 41 · 2015: 29 · 2014: 34 · 2013: 51 · 2012: 41
- FWCI
- 9.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- National Institute on Aging (AG-114412)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-41814, R01DK041814)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- plasma cortisol, circadian rhythm, aging, sex differences, hypothalamic-pituitary-adrenal axis, glucocorticoid exposure, stress and aging, acrophase, premenopausal women, sleep disorders in the elderly, cumulative stress
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Circadian Rhythm, Female, Humans, Hydrocortisone, Male, Middle Aged, Sex Characteristics, Body Mass Index
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