Smoking, Sex Hormones and Pregnancy

描述(申请人提供)：与男性相比，女性与吸烟相关的发病率和死亡率都更高，而且实现戒烟的难度也更大。性激素(特别是黄体酮、别孕酮和雌二醇)在动物和临床文献中都被认为对成瘾行为有影响。这些性激素在怀孕期间急剧增加，为进一步研究这种联系提供了一个理想的临床模型。因此，该项目的目标是研究性激素与妊娠期间吸烟相关症状的关系，以及更具对照的临床模型-口服避孕药。我们将通过评估两个具体的研究目标来实现这一目标：(1)研究孕酮(Prog)、别孕酮(Allo)水平和雌二醇/孕酮(E2/P)比率与随意吸烟期间吸烟相关症状的关系；(2)研究Prog、Allo和E2/P水平与夜间戒烟后吸烟相关症状和尼古丁反应的变化的关系。为了实现这些目标，将进行一项包含两个样本的研究：样本1将是怀孕16-20周或32-36周的孕妇(n=84)(选择两个时间点，以确保性激素水平有很大的变异性)。样本2将采用交叉设计来研究口服避孕药(OC)使用者样本(n=52)中孕酮的“低”和“高”水平。两个样本的参与者将完成相同的数据收集程序，包括提供唾液(用于应对压力的皮质醇)、尿液(尼古丁暴露)和血液(性激素)的生物样本，以及为期六天的生态瞬时评估。参与者还将在隔夜戒烟后完成尼古丁反应实验室会议。本研究有几个创新之处。具体地说，我们将是第一批研究性激素与怀孕期间吸烟相关症状的相关性的人之一，描述怀孕期间别孕酮的特征，并在已知性激素水平不同的两个临床模型(妊娠和OC使用者)中比较性激素对吸烟相关症状的影响。如果我们的假设得到证实，这项研究的结果将推进性激素在成瘾行为中的作用的文献。此外，这项研究 有可能为育龄妇女提供新的和创新的戒烟治疗方法。 公共卫生相关性：考虑到怀孕期间性激素的戏剧性变化，再加上性激素已被证明影响非怀孕女性临床人群的成瘾行为，该项目旨在以怀孕和口服避孕药的临床模型为临床模型，首批表征性激素升高与吸烟相关症状的关系。如果得到资助，这项研究的结果将直接为未来对育龄妇女的戒烟干预提供信息。

DESCRIPTION (provided by applicant): Compared to men, women are both at increased risk of smoking-related morbidity and mortality, and have increased difficulty achieving smoking abstinence. Sex hormones (specifically progesterone, allopregnanolone, and estradiol) have been implicated in both the animal and clinical literature as having an effect on addictive behaviors. These sex hormones increase dramatically during pregnancy, providing an ideal clinical model for further investigation into this association. Therefore, the objective of this project is to investigate the relationship between sex hormones and smoking-related symptomatology in pregnancy and, a more controlled clinical model, oral contraceptives. We will address this objective by assessing two specific study aims: (1) investigate the association between levels of progesterone (Prog), allopregnanolone (Allo) and the estradiol/progesterone (E2/P) ratio with smoking-related symptomatology during ad libitum smoking, and (2) examine the association between levels of Prog, Allo and E2/P with the changes in smoking-related symptomatology and response to nicotine following overnight smoking abstinence. These aims will be investigated by conducting one study with two samples: Sample 1 will be pregnant women (n=84) at either 16- 20 or 32-36 weeks gestation (two time points selected to ensure large variability in sex hormone levels). Sample 2 will incorporate a cross-over design to investigate "low" versus "high" levels of progesterone in a sample of oral contraceptive (OC) users (n=52). Participants in both samples will complete identical data collection procedures including providing biological samples of saliva (cortisol for stress), urine (nicotine exposure) and blood (sex hormones), as well as six days of ecological momentary assessments. Participants will also complete a nicotine response lab session following overnight abstinence. This study has several innovative aspects. Specifically, we will be among the first to investigate the association between sex hormones and smoking-related symptomatology during pregnancy, characterize allopregnanolone in pregnancy, and compare the effects of sex hormones on smoking-related symptomatology within two clinical models (pregnancy and OC users) known to have different levels of sex hormones. If our hypotheses are confirmed, the results of this study will advance the literature on the role of sex hormones in addictive behaviors. Further, this study has the potential to inform new and innovative smoking cessation treatments for women of childbearing age. PUBLIC HEALTH RELEVANCE: Given the dramatic changes in sex hormones during pregnancy, paired with the knowledge that sex hormones have been shown to impact addictive behaviors in the non-pregnant female clinical population, this project aims to be among the first to characterize the relationship of elevated sex hormones on smoking-related symptomatology using pregnancy and oral contraceptive use as clinical models. If funded, the results of this study will directly inform future smoking cessation interventions for women of childbearing age.