The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapy

Abstract Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age‐related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin therapy in elderly patients with insomnia. In adults, the melatonin onset typically occurs during low cortisol secretion. Administration of exogenous melatonin around dusk will shift the phase of the human circadian clock to earlier hours (advance phase shift) leading to phase advances in circadian rhythms (e.g., sleep, endogenous melatonin, cortisol). With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases and its peak occurs earlier in the night. In a randomized placebo‐controlled crossover study with 8 patients with insomnia aged 55 years and older, a group characterized by low and delayed melatonin production, administration of prolonged‐release melatonin in the evening was able to rectify the early onset cortisol production. This delay in nocturnal cortisol onset may explain in part the improvement in sleep quality in elderly patients with insomnia, in schizophrenics, and in depressed patients. Support of circadian pacemaker function by melatonin may provide a new strategy in the treatment of disorders related to impairments in the internal temporal order. The clinical benefit from a decrease in cortisol during the early part of the night may lie beyond the improvement of sleep into a better control of blood pressure, metabolism, and mood. Drug Dev. Res. 65:119–125, 2005. © 2005 Wiley‐Liss, Inc.