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Middle-Aged Men Show Higher Sensitivity of Sleep to the Arousing Effects of Corticotropin-Releasing Hormone Than Young Men: Clinical Implications

Sleep Research and Treatment Center, Department of Psychiatry (A.N.V., E.O.B., A.M.W., A.K.), and Department of Health Evaluation Sciences (H.-M.L.), Pennsylvania State University, Hershey, Pennsylvania 17033; Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (K.Z., G.P.C.), Bethesda, Maryland 20892; and Department of Psychiatry, Autonomous University (A.V.-B.), Madrid, Spain

Address all correspondence and requests for reprints to: Alexandros N. Vgontzas, M.D., Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: axv3{at}psu.edu

The prevalence of insomnia associated with emotional stress increases markedly in middle-age. Both the top and end hormones of the hypothalamic-pituitary-adrenal axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulness and inhibit slow wave (deep) sleep in experimental animals and man. The objective of this study was to test the hypothesis that middle-age is characterized by increased sensitivity to the sleep-disturbing effects of the hypothalamic-pituitary-adrenal axis.

We studied 12 healthy middle-aged (45.1 ± 4.9) and 12 healthy young (22.7 ± 2.8) men by monitoring their sleep by polysomnography for 4 consecutive nights, including in tandem 1 adaptation and 2 baseline nights and a night during which we administered equipotent doses of ovine CRH (1 µg/kg, iv bolus) 10 min after sleep onset. Analyses included comparisons within and between groups using multiple ANOVA and regression analysis.

Although both middle-aged and young men responded to CRH with similar elevations of ACTH and cortisol, the former had significantly more wakefulness and suppression of slow wave sleep compared with baseline sleep; in contrast, the latter showed no change. Also, comparison of the change in sleep patterns from baseline to the CRH night in the young men to the respective change observed in middle-aged men showed that middle-age was associated with significantly higher wakefulness and significantly greater decrease in slow wave sleep than in young age.

We conclude that middle-aged men show increased vulnerability of sleep to stress hormones, possibly resulting in impairments in the quality of sleep during periods of stress. We suggest that changes in sleep physiology associated with middle-age play a significant role in the marked increase of prevalence of insomnia in middle-age.

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