The purpose of this clinical trial on possible effects of nocturnal MEL administration in perimenopausal women was to find if MEL by itself modifies levels of hormones and produces changes of any kind, independently of age (42-62 years of age) and the stage of the menstrual cycle. It is accepted that a close link exists between the pineal gland, MEL, and human reproduction and that a relationship exists between adenohypophyseal and steroid hormones and MEL during the ovarian cycle, perimenopause, and menopause. Subjects took a daily dose of 3 mg synthetic melatonin or a placebo for 6 months. Levels of melatonin were determined from five daily saliva samples taken at fixed times. Hormone levels were determined from blood samples three times over the 6-month period. Our results indicate that a cause-effect relationship between the decline of nocturnal levels of MEL and onset of menopause may exist. The follow up controls show that MEL abrogates hormonal, menopause-related neurovegetative disturbances and restores menstrual cyclicity and fertility in perimenopausal or menopausal women. At present we assert that the six-month treatment with MEL produced a remarkable and highly significant improvement of thyroid function, positive changes of gonadotropins towards more juvenile levels, and abrogation of menopause-related depression.