Testing Effects of Melatonin on Uterine Contractions in Women

Project Summary/Abstract Spontaneous labor in pregnant women is more often initiated at night when melatonin levels are normally high. Melatonin administration in vitro increases uterine contractility, but whether exogenous melatonin can increase uterine contractions in humans is unknown. Whether melatonin administration can increase uterine contractions in the presence of light exposure at night, which suppresses melatonin levels, is also not known. Light exposure at night is common both at home and in hospitalized settings, and the suppressed melatonin levels may be associated with lower uterine contractions. Therefore, we propose to test the causal relationship between circulating melatonin concentrations and uterine contractions during the day and during the evening. This basic physiological information is needed before obstetric interventions using melatonin can be designed. In our recent studies in 28 late-term pregnant women, we induced significant (40%) melatonin suppression using monochromatic short-wavelength (blue/green) light exposure at night. In the control condition, the women were exposed to long-wavelength (red) light, which did not suppress melatonin levels. The two light exposure conditions created a range of circulating melatonin levels in which we found a significant positive relationship between circulating melatonin concentration and the number of objectively measured uterine contractions. Therefore, we propose to test 3 hypotheses in controlled inpatient hospital conditions by measuring uterine contractions in full-term pregnant women after exogenous melatonin: (i) exogenous melatonin during the day when endogenous melatonin levels are almost undetectable will increase uterine contractions, (ii) exogenous melatonin administration at night during light exposure-induced suppression of normally high concentrations of endogenous melatonin will increase uterine contractions; (iii) there is a positive correlation between circulating melatonin levels and number of uterine contractions. The first experiment is a randomized double-blind trial in which participants will receive a 0.0 mg (placebo), 0.5 mg (physiological), or a 3.0 mg (supraphysiological) dose of melatonin in the morning (~4 h after wake). The second experiment is a randomized double-blind trial in which participants will be exposed to monochromatic long-wavelength and a placebo pill during the evening on Night1 and then short-wavelength light with placebo or 0.5 mg dose of melatonin during the evening on Night2. In both experiments, participants will be ≥40 weeks pregnant women and uterine contractions will be monitored continuously using tocometry. Data from both experiments will be used for testing the correlation hypothesis. Better understanding of the physiological role of melatonin in modulating uterine contractions is important for designing interventions that can improve obstetric care. Ramifications of these physiological findings for the practice of obstetrics could be dramatic, including the use of pharmaceutical-grade melatonin, its antagonists, or light exposure that alters endogenous melatonin levels to modulate contractions. These low cost and low risk interventions could also eventually be used in facilities with limited resources to improve labor and delivery.