Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: Clinical implications

The prevalence of insomnia associated with emotional stress increases marke dly in middle-age. Both the top and end hormones of the hypothalamic-pituit ary-adrenal axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulne ss 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 chara cterized by increased sensitivity to the sleep-disturbing effects of the hy pothalamic-pituitary-adrenal axis. We studied 12 healthy middle-aged (45.1 +/- 1.9) and 12 healthy young (22.7 +/- 2.8) men by monitoring their sleep by polysomnography for 4 consecutiv e nights, including in tandem 1 adaptation and 2 baseline nights and a nigh t during which we administered equipotent doses of ovine CRH (1 mug/kg, iv bolus) 10 min after sleep onset. Analyses included comparisons within and b etween groups using multiple ANOVA and regression analysis. Although both middle-aged and young men responded to CRH with similar eleva tions of ACTH and cortisol, the former had significantly more wakefulness a nd suppression of slow wave sleep compared with baseline sleep; in contrast , the latter showed no change. Also, comparison of the change in sleep patt erns from baseline to the CRH night in the young men to the respective chan ge observed in middle-aged men showed that middle-age was associated with s ignificantly 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 s tress hormones, possibly resulting in impairments in the quality of sleep d uring periods of stress. We suggest that changes in sleep physiology associ ated with middle-age play a significant role in the marked increase of prev alence of insomnia in middle-age.