Testing Effects of Melatonin on Uterine Contractions in Women

测试褪黑激素对女性子宫收缩的影响

• 批准号: 10342836
• 负责人: Elizabeth B. Klerman
• 金额: $ 75.35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10342836
• 关键词: Affect; Agonist; Binding; Birth; Clinical; Data; Discipline of obstetrics; Dose; Double-Blind Method; Double-blind trial; Exposure to; Goals; Home; Hormones; Hospitals; Hour; Human; In Vitro; Individual; Inpatients; Intervention; Light; Lighting; Measures; Melatonin; Melatonin Receptors; Midwifery; Monitor; Muscle Contraction; Neurosecretory Systems; Participant; Pharmacologic Substance; Physiological; Pilot Projects; Placebos; Pregnancy; Pregnant Uterus; Pregnant Women; Protocols documentation; Randomized; Research Project Grants; Resources; Risk; Role; Testing; Up-Regulation; Uterine Contraction; Variant; Woman; Work; antagonist; circadian; cost; design; experimental study; improved; in vitro Model; mRNA Expression; myometrium; obstetric care; pill; protein expression; reproductive; therapy design; uterine contractility

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.

项目总结/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。 高体外给予褪黑素可增加子宫收缩力，但外源性褪黑素是否能 人类子宫收缩增加是未知的。褪黑激素给药是否能增加子宫 也不知道在夜间存在抑制褪黑激素水平的光暴露的情况下的收缩。 无论是在家里还是在医院，夜间暴露在光线下都很常见， 水平可能与子宫收缩较低有关。因此，我们建议检验因果关系 循环褪黑激素浓度与白天和晚上子宫收缩之间的关系。 在设计使用褪黑激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%）的褪黑激素抑制 使用单色短波长（蓝色/绿色）光在夜间曝光。在对照组中， 暴露于长波长（红色）光，这并不抑制褪黑激素水平。两个曝光 条件创造了一系列循环褪黑激素水平，其中我们发现了显着的正相关关系 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，我们建议在控制住院条件下，通过测量子宫 外源性褪黑激素对足月妊娠妇女宫缩的影响：（i）白天外源性褪黑激素 当内源性褪黑激素水平几乎检测不到时，将增加子宫收缩，（ii）外源性 褪黑激素在夜间给药期间，光照诱导抑制正常高浓度的 内源性褪黑激素会增加子宫收缩;（iii）循环中的褪黑激素与子宫收缩之间存在正相关性。 褪黑激素水平和子宫收缩次数。第一个实验是一个随机双盲试验， 受试者将接受0.0 mg（安慰剂）、0.5 mg（生理）或3.0 mg（超生理）剂量 早上（醒来后约4小时）服用褪黑激素。第二个实验是随机双盲试验， 受试者将在第1天晚上暴露于单色长波长和安慰剂药丸 然后在Night2晚上用安慰剂或0.5 mg剂量的褪黑激素进行短波长光照射。无论是 在实验中，参与者将是≥ 40周的孕妇，并将监测子宫收缩 持续使用催产素。来自两个实验的数据将用于检验相关性假设。 更好地了解褪黑激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。这些生理发现的分支， 产科实践可能是戏剧性的，包括使用药物级褪黑激素，其拮抗剂，或 光暴露改变内源性褪黑激素水平以调节收缩。这些低成本、低风险 干预措施最终也可用于资源有限的设施，以改善分娩和分娩。