The effects of exogenous melatonin on endocrine function in man.

At two different times of year (spring and autumn) an oral preparation of the pineal neurohormone melatonin, or placebo, was administered to 12 healthy volunteers (10 men and two women in spring: the same group minus one man in autumn) daily at 1700 h for 1 month (spring), or 3 weeks (autumn) using a double-blind cross-over protocol. The daily dose was 2 mg melatonin in 5 ml corn-oil, and placebo consisted of the vehicle only. In spring the anterior pituitary hormones LH, PRL, GH together with T4, cortisol, testosterone and melatonin were measured at 1- to 6-h intervals for 24 h in plasma on the day following the last dose. In autumn PRL, cortisol and melatonin levels were measured on the last day of treatment. Subjective fatigue, mood and sleep records were kept throughout the studies. Melatonin increased early evening fatigue and actual sleep, but had no effect on mood: these results are reported in full elsewhere. Melatonin administration had no effect on the levels or 24-h rhythm of LH, GH, T4, testosterone or cortisol. An earlier fall in the nocturnal PRL was observed on both occasions. Overall PRL levels were higher in spring than in autumn. In five of the subjects, the secretion of endogenous melatonin was advanced by 1-3 h in the presence of exogenous melatonin. These observations suggest that the potential therapeutic use of melatonin as a hypnotic or in the treatment of jet lag is unlikely to be complicated by undesirable endocrine effects.