Progesterone Augmentation for Smoking Cessation in Women

 描述（申请人提供）：尼古丁成瘾仍然是发达国家可预防的主要死因，美国估计有435，000例过早死亡。尽管有有效的药物治疗，但70%至90%试图戒烟的吸烟者在治疗后一年内重新吸烟。妇女可能更难实现和保持戒烟，因为妇女戒烟者与曾经吸烟者的比率（戒烟率）（55.2%）低于男子（59.2%）。与男性相比，女性更容易受到吸烟并发症的影响，尤其是肺癌。在美国，死于肺癌的女性人数超过乳腺癌和结肠癌的总和。这些发现支持了针对女性吸烟者的有效治疗的必要性。一种这样的方法可能包括使用孕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，那些在内源性血浆孕酮水平高时试图戒烟的人，比那些在孕酮水平低时试图戒烟的人复发吸烟的风险更低。我们小组的工作指出了孕酮的潜在治疗作用，因为孕酮减弱了最近戒烟的女性吸烟者对香烟的渴望和吸烟的愉悦效果。综上所述，这些发现使我们假设孕激素可能会增加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与安慰剂相比，黄体酮治疗的安全性、耐受性和有效性，并与经皮尼古丁贴片（TNP）联合用于定期骑自行车的女性戒烟。我们提出了一个为期8周的试点临床试验，其中50名吸烟者将被随机分配到黄体酮（200毫克，每日两次）或安慰剂。所有受试者在参与研究期间还将接受TNP和戒烟行为治疗。吸烟者将尝试戒烟一周后开始孕激素和TNP治疗。主要结局指标是治疗结束时以及1个月和3个月随访时间点的长期戒烟率和7天戒烟率。与更常用的合成孕激素相反，孕激素是一种具有良好安全性的天然激素，其作为女性新型戒烟药物的用途是非常可行的。

 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.