Influence of synthetic sex hormones on alcohol effects and consumption in women

项目摘要/摘要 有大量的临床前证据表明，卵巢激素影响神经生物系统， 调解药物和酒精奖励，这可能有助于增强女性对AUD的易感性；研究 表明雌激素促进而黄体酮反对酒精奖励。然而，几乎没有确凿的经验证据。 来自对自然循环女性酒精影响和饮酒的受控人体研究的数据。因此， 我们对如何预防和更好地治疗女性AUD的理解受到了损害，新的研究 我们需要一些方法。最近的研究结果表明，月经周期中激素水平较高的时期是 与酗酒增加有关。口服避孕药(OC)是含有合成卵巢的药物 抑制与月经周期有关的内源性激素波动的激素。所以，内源性雌激素 黄体酮和外源性雌二醇在整个周期中保持在较低水平，而合成孕酮和 稳定。服用OC的女性与自然骑自行车的女性酒精影响和饮酒的比较研究 女性将促进我们对卵巢激素如何影响AUD的理解，因为有更大的力量 在低变异性的背景下检测卵巢激素的影响，我们也可以比较相对的 荷尔蒙稳定性与变异性。这项研究的长期目标是更好地了解卵巢激素如何 影响女性的酒精使用、滥用和AUD的进程。拟议研究的目标是 使用受控的实验室程序确定OC如何影响酒精效果和饮酒量。在工作中 假说是口服避孕药中的合成孕激素模仿自然孕酮的作用。 减弱酒精的奖励和激励作用，以及酒精消费。理由是 确定合成卵巢激素(OC)对酒精效应的影响将提供一个强有力的框架 寻求以妇女为重点的新的预防和治疗方法。这一假设将由两个人进行检验 具体目标：1)确定口服避孕药对酒精剂量依赖效应的影响 使用受控人体实验室程序的自我给药，以及2)确定 自然和合成卵巢激素的循环水平以及酒精的影响和消费。这项计划 这项研究具有创新性，因为它将转移卵巢激素对酒精影响的研究重点 从内源激素到外源激素的反应和消耗。这也将是第一个对照研究 对使用OC的女性的酒精影响和饮酒进行研究。该项目意义重大，因为它将在很大程度上 加深我们对卵巢激素如何影响酒精效应和饮酒的理解，饮酒是一个重要因素 这导致了澳元的性别差异。这一发现将具有临床意义，因为它们适用于大型 目前使用荷尔蒙避孕药的美国女性比例将突出这项被忽视的研究 合成荷尔蒙和澳元面积。最后，积极的发现，高度稳定的合成孕激素抑制 酒精奖励将为以女性机制为重点的疗法的发展提供一个框架。

PROJECT SUMMARY/ABSTRACT There is ample preclinical evidence showing that ovarian hormones influence the neurobiological systems that mediate drug and alcohol reward which may contribute to the enhanced vulnerability of women to AUD; studies show that estrogen promotes and progesterone opposes alcohol reward. Yet, there is little conclusive empirical data from controlled human studies of alcohol effects and consumption in naturally-cycling women. Consequently, our understanding of how to prevent and better treat AUD among women is compromised, and new research approaches are needed. Recent findings suggest that periods of high hormonal flux during the menstrual cycle are associated with increased binge drinking. Oral contraceptives (OC) are medications containing synthetic ovarian hormones that suppress menstrual cycle-related fluctuations in endogenous hormones. So, endogenous estrogen and progesterone, and exogenous estradiol remain low across the cycle while synthetic progestins are high and stable. Studies of alcohol effects and consumption among women using OC in comparison to naturally cycling women will advance our understanding of how ovarian hormones influence AUD because there is greater power to detect effects of ovarian hormones against a background of low variability, and we can also compare relative hormone stability vs. variation. The long-term goal of this research is to better understand how ovarian hormones influence alcohol use, abuse, and the course of AUD among women. The objective of the proposed research is to determine how OC influence alcohol effects and consumption using controlled laboratory procedures. The working hypothesis is that synthetic progestins in oral contraceptives mimic the effects of natural progesterone thereby attenuating the rewarding and motivational effects of alcohol, and alcohol consumption. The rationale is that determining the influence of synthetic ovarian hormones (OC) on alcohol effects will provide a strong framework to pursue novel women-focused prevention and treatment approaches. The hypothesis will be tested by two specific aims; 1) Determine the influence of oral contraceptives on dose-dependent effects of alcohol, and alcohol self-administration using controlled human laboratory procedures, and 2) Determine the relationship between circulating levels of natural and synthetic ovarian hormones and alcohol effects and consumption. This plan of research is innovative because it will shift the focus of research on the effects of ovarian hormones on alcohol responses and consumption from endogenous to exogenous hormones. This will also be the first controlled study of alcohol effects and consumption among women using OC. The project is significant because it will substantially advance our understanding of how ovarian hormones influence alcohol effects and drinking, an important factor that contributes to sex differences in AUD. The findings will be clinically significant as they apply to a large proportion of US women who currently use hormonal contraceptives and will highlight the overlooked research area of synthetic hormones and AUD. Finally, positive findings that high stable synthetic progestin dampens alcohol reward will provide a framework for the development of therapies focused on female mechanisms.