Progesterone Augmentation for Smoking Cessation in Women

 描述(申请人提供)：尼古丁成瘾在发达国家仍然是主要的可预防的死亡原因，在美国估计有43.5万人过早死亡。尽管有有效的药物治疗，70%到90%的吸烟者试图在治疗后一年内戒烟。女性实现和维持戒烟的难度可能更大，因为以前吸烟者与曾经吸烟者的比率(戒烟率)女性(55.2%)低于男性(59.2%)。与男性相比，女性更容易受到吸烟并发症的影响，最明显的是肺癌。在美国，女性死于肺癌的人数超过了乳腺癌和结肠癌的总和。这些发现支持了为女性吸烟者量身定做有效治疗的必要性。其中一种方法可能包括使用黄体酮来增加目前可用的戒烟治疗。来自临床研究的数据表明，在月经周期规律的女性中，那些试图在内源性血浆孕酮水平较高时戒烟的人，比那些试图在黄体酮水平较低时戒烟的人，再次吸烟的风险更低。我们小组的工作指出了黄体酮的潜在治疗作用，因为在最近戒烟的女性吸烟者中，黄体酮既能减轻对香烟的渴望，又能减轻吸烟的愉悦效果。综上所述，这些发现让我们假设，黄体酮可能会增强定期骑自行车的女性戒烟治疗的疗效。这项概念验证研究将测试黄体酮治疗的安全性、耐受性和有效性，与安慰剂相比，联合尼古丁贴片(TNP)用于定期骑自行车的女性戒烟。我们提出了一项为期8周的试点临床试验，将50名吸烟者随机分为黄体酮(每天两次，200毫克)或安慰剂。所有参与者还将在参与研究期间接受TNP和戒烟行为治疗。吸烟者将在黄体酮和TNP治疗开始一周后尝试戒烟。主要的结果指标将是在治疗结束时以及在1个月和3个月的随访时间点上戒烟的持续时间和7天的流行率。与更常用的合成孕激素相比，黄体酮是一种具有良好安全性的天然激素，它作为一种新型的女性戒烟药物是非常可行的。

 DESCRIPTION (provided by applicant): Nicotine addiction continues to be the main preventable cause of death in developed countries, with an estimated 435,000 premature deaths in the U.S. Despite the availability of effective pharmacotherapies, 70 to 90% of smokers who attempt to quit resume smoking within a year of treatment. Women may have greater difficulty achieving and sustaining abstinence from smoking, as the ratio of former smokers to ever smokers (quit ratio) is lower in women (55.2%) than in men (59.2%). Women, compared to men, are more vulnerable to the complications of smoking, most notably lung cancer. In the US, lung cancer kills more women than breast and colon cancer combined. These findings support the need for effective treatments tailored for female smokers. One such approach may include use of progesterone to augment currently available smoking cessation treatments. Data from clinical studies suggest that in women with regular menstrual cycles, those who try to quit smoking when endogenous plasma progesterone levels are high, have a lower risk of relapse to smoking than those who try to quit when progesterone levels are low. Work from our group points to a potential therapeutic role for progesterone, in that progesterone attenuates both craving for cigarettes and the pleasurable effects of smoking among recently abstinent female smokers. Taken together, these findings led us to hypothesize that progesterone may augment the efficacy of smoking cessation treatments in regularly cycling women. This proof-of-concept study will test the safety, tolerability, and effectiveness of progesterone treatment, compared to placebo, in combination with transdermal nicotine patch (TNP) for smoking cessation in regularly cycling women. We propose an 8-week, pilot, clinical trial in which 50 smokers will be randomized to progesterone (200 mg twice daily) or placebo. All participants will also receive TNP and behavioral treatment for smoking cessation during study participation. Smokers will attempt to quit smoking one week after initiation of progesterone and TNP treatment. The main outcome measures will be the prolonged and 7-day point prevalence of smoking abstinence at the end of treatment and at 1- and 3-month follow-up time points. Progesterone, in contrast to the more commonly used synthetic progestins, is a natural hormone with excellent safety profile and its use as a novel smoking cessation medication in women is highly feasible.