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

合成性激素对女性酒精作用和消费的影响

• 批准号: 10240734
• 负责人: EMMA CHILDS
• 金额: $ 18.99万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-20 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240734
• 关键词: Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Area; Attenuated; Behavior; Behavioral; Blood specimen; Brain; Clinical; Clinical Research; Consumption; Controlled Study; Data; Development; Disease; Dose; Estradiol; Estrogens; Ethinyl Estradiol; Exhibits; Female; Goals; Gonadal Steroid Hormones; Hormonal; Hormone use; Hormones; Human; Intrauterine Devices; Knowledge; Laboratory Procedures; Luteal Phase; Mediating; Menstrual cycle; Midbrain structure; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Oral Contraceptives; Ovarian; Ovarian hormone; Ovulation; Participant; Pattern; Pharmaceutical Preparations; Phase; Predisposition; Prevention; Prevention approach; Production; Progesterone; Public Health; Reporting; Research; Rewards; Risk; Role; Self Administration; Sex Differences; Strategic Planning; Study Subject; Synthetic Progestogens; System; Taste Perception; Testing; Treatment outcome; United States National Institutes of Health; Variant; Woman; Women' s Health; alcohol abuse therapy; alcohol effect; alcohol response; alcohol reward; alcohol use disorder; base; binge drinking; clinically significant; drinking; drug reward; gender difference; hormonal contraception; improved; innovation; novel; novel strategies; pill; pre-clinical; prevent; proliferative phase Menstrual cycle; sex; therapy development; xenoestrogen

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.

项目概要/摘要 有充足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，这可能会加剧妇女对澳元的脆弱性；研究 表明雌激素促进酒精奖赏，而黄体酮则反对酒精奖赏。然而，几乎没有确凿的实证 来自受控人体研究的数据，该研究涉及自然循环女性的酒精影响和饮酒量。最后， 我们对如何预防和更好地治疗女性 AUD 的理解受到损害，新的研究 需要采取一些方法。最近的研究结果表明，月经周期中荷尔蒙高通量的时期是 与酗酒增加有关。口服避孕药（OC）是含有合成卵巢的药物 抑制与月经周期相关的内源激素波动的激素。所以，内源性雌激素 和黄体酮和外源性雌二醇在整个周期中保持较低水平，而合成孕激素则较高且 稳定的。与自然骑行相比，使用 OC 的女性的酒精影响和消费量研究 女性将增进我们对卵巢激素如何影响 AUD 的理解，因为她们有更大的力量 检测卵巢激素在低变异性背景下的影响，我们还可以比较相对 激素稳定性与变化。这项研究的长期目标是更好地了解卵巢激素如何 影响女性的饮酒、滥用和 AUD 病程。拟议研究的目的是 使用受控实验室程序确定 OC 如何影响酒精效应和消费。工作中 假设口服避孕药中的合成孕激素模仿天然孕激素的作用，从而 减弱酒精和饮酒的奖励和激励作用。理由是 确定合成卵巢激素（OC）对酒精影响的影响将提供一个强有力的框架 寻求以妇女为中心的新型预防和治疗方法。该假设将由两个人来检验 具体目标； 1) 确定口服避孕药对酒精的剂量依赖性影响以及酒精的影响 使用受控人体实验室程序进行自我管理，以及 2) 确定之间的关系 天然和合成卵巢激素的循环水平以及酒精的影响和消耗。这个计划的 这项研究具有创新性，因为它将把研究重点转移到卵巢激素对酒精的影响上 从内源性激素到外源性激素的反应和消耗。这也将是第一个对照研究 使用 OC 的女性的酒精影响和消费情况。该项目意义重大，因为它将极大地 增进我们对卵巢激素如何影响酒精影响和饮酒的理解，这是一个重要因素 这导致了澳元的性别差异。这些发现将具有临床意义，因为它们适用于大量 目前使用激素避孕药的美国女性比例，将强调被忽视的研究 合成激素和澳元领域。最后，积极的发现表明高稳定的合成孕激素抑制 酒精奖励将为开发针对女性机制的疗法提供一个框架。