Progesterone for Postpartum Smokers: Feasibility, Breastfeeding and Infant Safety

描述(申请人提供)：在西方国家，吸烟是主要的可预防的死亡原因，仅在美国每年就造成超过43万人死亡。临床和流行病学研究表明，当内源性孕酮水平较高时，女性通常会在怀孕期间减少吸烟。然而，至少有一半的人在分娩后几周内恢复怀孕前的吸烟水平，并在孕酮水平下降时恢复。产后吸烟的妇女会增加她们及其后代的健康风险。在产后妇女中，没有明确的行为或药物治疗被确定为安全有效的戒烟方法。此外，产后妇女和产科提供者都不愿使用传统的禁烟药物，因为如果母亲正在哺乳，这可能会导致新生儿接触到吸烟药物。鉴于这些担忧，非常有必要开发为怀孕前吸烟的产后妇女量身定做的复发预防治疗。来自临床前和临床研究的数据表明，孕酮可能有效地防止非产后妇女再次吸烟，并可能被产后妇女及其提供者接受。先前的研究表明，在最近戒烟的女性吸烟者中，外源性给药既减轻了对香烟的渴望，也减轻了吸烟的主观奖励效应。这些发现使我们假设孕酮可能对产后妇女具有预防复发的疗效。我们建议进行一项为期8周的随机试点研究，以评估黄体酮的安全性和初步疗效。这将是一项可行性研究，将在40名产后吸烟者中比较黄体酮(200毫克/天)和安慰剂预防复发的效果。我们将评估其可行性和安全性，包括对母乳喂养和通过母乳接触的婴儿的潜在影响，以及在治疗8周后和在方案结束后3个月的随访中戒烟的7天时点流行率。如果数据显示孕酮有效，我们将在更大的临床试验中测试干预措施。黄体酮治疗，如果最终被发现是有治疗作用的，可以由习惯于使用黄体酮作为治疗剂的提供者在产科环境中部署。因此，拟议的项目有可能对新妈妈及其子女的健康产生重大影响。

DESCRIPTION (provided by applicant): Smoking is the main preventable cause of mortality in Western countries, contributing to over 430,000 deaths a year in the U.S. alone. Clinical and epidemiological studies show that women often decrease smoking in pregnancy, when endogenous progesterone levels are high. However, at least half resume pre-pregnancy smoking levels within weeks after delivery and when progesterone levels drop. Postpartum women who smoke increase their health risks and that of their offspring. No behavioral or medication treatments are clearly established as safe and effective for smoking cessation in postpartum women. Further, there is reluctance on the part of both postpartum women and obstetrical providers to use traditional anti-smoking medications since this may lead to neonatal exposure if the mother is breastfeeding. Given these concerns, there is a great need to develop relapse prevention treatments that are tailored for postpartum women with pre-conception smoking. Data from preclinical and clinical studies suggest that progesterone may be effective in preventing relapse to smoking in non-postpartum women, and may be acceptable to postpartum women and their providers. Prior work has shown that exogenous administration attenuates both craving for cigarettes and the subjective rewarding effects of smoking among recently abstinent female smokers. These findings led us to hypothesize that progesterone may have efficacy as a relapse prevention treatment for postpartum women. We propose an 8-week, randomized pilot study to evaluate the safety and initial efficacy of progesterone. This will be a feasibility study that will compare progesterone (200 mg/day) to placebo for relapse prevention in 40 postpartum smokers. We will assess the feasibility and safety, including the potential effects on breastfeeding and infants exposed via breast milk, in addition to 7-day point prevalence of smoking abstinence after 8 weeks of treatment and at follow-up, 3-months after the end of the protocol. If data suggest efficacy for progesterone, we will test the intervention i a larger clinical trial. Progesterone treatment, if ultimately found to be therapeutic, could be deployed in an obstetrical setting by providers that are accustomed to the use of progesterone as a therapeutic agent. Accordingly, the proposed project has the potential to make a major impact on the health of new mothers and their children.