Testing Effects of Melatonin on Uterine Contractions in Women

项目摘要/摘要 孕妇的自然分娩通常在夜间开始，此时褪黑激素水平正常。 很高。体外给予褪黑素可增加子宫收缩，但外源性褪黑素是否能 人类子宫收缩的增加是未知的。服用褪黑素是否会增加子宫 夜间暴露在光线下的宫缩抑制褪黑激素水平，也是未知的。 夜间光照在家中和住院环境中都很常见，褪黑激素受到抑制 这一水平可能与较低的子宫收缩有关。因此，我们建议检验因果关系 在白天和晚上循环中的褪黑素浓度与子宫收缩之间的关系。 在设计使用褪黑素的产科干预措施之前，需要这些基本的生理信息。 在我们最近对28名晚期孕妇的研究中，我们诱导了显著(40%)的褪黑素抑制。 在夜间使用单色短波(蓝/绿)光曝光。在控制条件下，女性 暴露在长波长(红色)光下，这不会抑制褪黑激素水平。两种光线的曝光 条件创造了一系列循环中的褪黑素水平，我们在其中发现了显著的正相关关系 循环褪黑激素浓度和客观测量的子宫收缩次数之间的关系。 因此，我们建议在受控住院条件下通过测量子宫来检验3个假说。 足月妊娠妇女在外源性褪黑素后的宫缩：(I)日间外源性褪黑素 当内源性褪黑素水平几乎检测不到时，会增加子宫收缩，(Ii)外源性 光暴露期间夜间给予褪黑素可抑制正常浓度的褪黑素 内源性褪黑素会增加子宫收缩；(三)循环中存在正相关 褪黑素水平和子宫收缩次数。第一个实验是#年的随机双盲试验 哪些参与者将接受0.0毫克(安慰剂)、0.5毫克(生理)或3.0毫克(超生理)剂量 早晨(清醒后约4小时)褪黑激素的水平。第二个实验是随机双盲试验， 参与者将在Night1晚上接触到单色长波和安慰剂药片 然后在Night2的晚上，用短波长光照射安慰剂或0.5 mg剂量的褪黑素。在这两个地方 实验中，参与者将对怀孕40周的≥妇女和子宫收缩进行监测 连续使用生育测定法。这两个实验的数据将被用来检验相关性假说。 更好地了解褪黑素在调节子宫收缩中的生理作用对于 设计能够改善产科护理的干预措施。这些生理学发现的分支对 产科的实践可能是戏剧性的，包括使用药用级别的褪黑素、其拮抗剂，或 光暴露改变内源性褪黑素水平以调节收缩。这些低成本和低风险 干预措施最终也可能用于资源有限的设施，以改善劳动力和分娩。

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.