Smoking, Sex Hormones and Pregnancy

描述（由申请人提供）：与男性相比，女性吸烟相关的发病率和死亡率风险增加，实现戒烟的难度增加。性激素（特别是孕酮、别孕烯醇酮和雌二醇）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，为进一步研究这种关联提供了理想的临床模型。因此，本项目的目的是调查性激素和吸烟相关的妊娠期阴道病之间的关系，以及一个更受控制的临床模型，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）研究在随意吸烟期间孕酮（Prog）、别孕烯醇酮（Allo）水平和雌二醇/孕酮（E2/P）比率与吸烟相关性前列腺炎之间的关联，以及（2）研究Prog、Allo和E2/P与整夜戒烟后吸烟相关的代谢和尼古丁反应的变化。将通过使用两个样本进行一项研究来研究这些目标：样本1将是妊娠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的较大变异性）。样本2将采用交叉设计，以调查口服避孕药（OC）使用者样本（n=52）中孕酮的“低”与“高”水平。两个样本中的参与者将完成相同的数据收集程序，包括提供唾液（应激皮质醇）、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。参与者还将在整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。具体来说，我们将是第一个调查怀孕期间性激素和吸烟相关的生殖系统之间的关联，描述怀孕期间的别孕烯醇酮，并比较性激素对吸烟相关的生殖系统的影响在两个临床模型（怀孕和OC用户）已知具有不同水平的性激素。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。 公共卫生相关性：考虑到怀孕期间性激素的巨大变化，以及性激素已被证明会影响非怀孕女性临床人群中的成瘾行为的知识，该项目旨在成为第一个使用妊娠和口服避孕药作为临床模型来描述性激素升高与吸烟相关的成瘾性的关系。如果获得资助，这项研究的结果将直接为育龄妇女未来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.