Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia

Objective To evaluate the effects of ramelteon, an MT1/MT2 melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia. Methods This was a double-blind, placebo-controlled, trial of adults (18-45 years) with chronic insomnia. Subjects received either ramelteon 16 mg or placebo nightly for 6 months. Hormonal measures of the thyroid, reproductive, and adrenal axes were analyzed monthly and compared with baseline and placebo values. Results While isolated changes were detected at some time points, there were no consistent statistically significant differences between treatments on measures of thyroid function (total T4, free T4, TSH, and total T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine measures [LH, FSH, estradiol (women), total, and free testosterone (men)]. Prolactin concentrations were increased overall in women in the ramelteon group compared with placebo (p = 0.003). No clinical effects of elevated prolactin were reported; average menstrual cycle length, duration of menses, and ovulation probability did not differ between groups. Conclusions Long-term exposure to ramelteon 16 mg, a potent melatonin receptor agonist, resulted in mild, transient increase in prolactin, in women only, that were not associated with measurable reproductive effects. There were no consistent changes in other endocrine measures. Copyright (C) 2008 John Wiley & Sons, Ltd.