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Higher Levels and Blunted Diurnal Variation of Cortisol in Frail Older Women

Divisions of ¹ Geriatric Medicine and Gerontology and ² Endocrinology and Metabolism, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
³ The Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.
⁴ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
⁵ Division of Endocrinology, Diabetes and Metabolism, School of Medicine, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia.

Address correspondence to Ravi Varadhan, PhD, 2024 E. Monument Street, Suite 2-700, Baltimore, MD 21205. E-mail: rvaradhan{at}jhmi.edu

Background. Frailty is an important geriatric condition with increased vulnerability to stressors (e.g., infection and injury) and for developing functional dependence and mortality. Impairments in signaling pathways, including neuroendocrine alterations, are thought to be involved in the etiology of frailty, but have not been well characterized to date. We evaluated whether higher levels and blunted diurnal variation of salivary cortisol are cross-sectionally associated with frailty burden.

Methods. Two hundred fourteen community-dwelling women, 80–90 years old, from the Women's Health and Aging Study participated in this study between 2004 and 2005. Seven saliva samples were collected for cortisol measurement over a 24-hour period. Main outcomes were awakening, evening, and overall mean cortisol; diurnal amplitude; and rate of decline of cortisol level during morning hours. All cortisol concentrations were log-transformed. Frailty burden was calculated, based on a previously validated tool, as the number (0–5) of the following criteria present: weakness, exhaustion, weight loss, slowness, and inactivity.

Results. Significant positive associations were found between frailty burden and evening cortisol (β = 0.11, p =.04), and between frailty burden and 24-hour mean cortisol (β = 0.07, p =.03). Increasing frailty burden was significantly associated with smaller declines in cortisol during morning hours (β = 0.04, p =.02). Frailty burden of 2 was associated with a smaller diurnal amplitude (β = –0.34, p =.03). Awakening cortisol was not significantly associated with frailty burden (β = 0.01, p =.8). All analyses included adjustments for several important confounders.

Conclusions. Our findings provide the first epidemiological evidence that higher levels and blunted diurnal variation of cortisol may be involved in the vulnerability and clinical presentation observed in frail older women.

Key Words: Frailty • Salivary cortisol • Diurnal rhythm • HPA axis • Evening cortisol

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