738 Effects of exogenous melatonin on sleep, circadian rhythms, and mood in women with premenstrual dysphoric disorder

Abstract

Abstract Introduction Most women with premenstrual dysphoric disorder (PMDD) report sleep disturbances. Our group found normal polysomnographic (PSG) sleep efficiency and increased slow wave sleep (SWS) across the menstrual cycle in women with PMDD and insomnia compared to controls. Reduced melatonin levels were found in PMDD women compared to controls, with reduced secretion during their luteal phase (LP) compared to follicular phase (FP). Here, we investigated the effects of exogenous melatonin in the patients we previously studied. Methods Five patients (age, mean: 33.6, SD: 2.7) diagnosed prospectively with PMDD and insomnia participated in the study. Following a baseline assessment, patients took 2 mg of slow-release melatonin 1h before bedtime during their LP for three consecutive menstrual cycles. At baseline (treatment-free condition), patients spent every third night of their menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analogue scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual symptoms (PRISM), subjective sleep and ovarian hormones (estrogen and progesterone). Participants also underwent two 24-hour intensive physiological monitoring (during the FP and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. Results In the intervention condition compared to baseline, we found increased urinary aMt6 (p<0.001), reduced objective SOL (p=0.01), SWS (p<0.001) and increased Stage 2 sleep (p<0.001). Increased urinary aMt6 was associated with reduced SWS (r=-0.51, p<0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p=0.01). Ovarian hormones were comparable between the conditions (p≥0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p=0.02) and the PRISM (p<0.001). Conclusion We have shown normalization of SWS and reduction in self-reported mood and somatic symptoms after administrating exogenous melatonin in women with PMDD. These findings support a role for disturbed melatoninergic system in PMDD that can be partially corrected by exogenous melatonin. Support (if any) This study was supported by the Canadian Institutes of Health Research (CIHR)