【作者】 韩燕清；

【导师】 牛建昭； 刘建平；

【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2011， 博士

【摘要】 由于治疗多囊卵巢综合征(PCOS)的许多西药多有不同程度的副作用且药价昂贵,因此相对来说经济安全的中药被较为普遍地用于PCOS的治疗,或被用来与西药结合使用以提高治疗效果。迄今为止中药在治疗PCOS中的应用规律及治疗效果尚有待于系统全面的分析。本研究从1980年到2009年间发表的临床实验和系列病历研究文献中收集数据,通过建立关联数据库,对中药治疗PCOS文献数据进行了两个方面的分析。文献研究一是通过系统分析方法来研究中药对PCOS的治疗效果。相关文献检索使用www.ilib.cn和PUBMED。检索年代为1980年到2008年。关键词为“多囊卵巢综合征(PCOS)".“中医”、“中药”、“克罗米芬(Clomid citrate)"、“文献系统分析”和"Meta-analysis"。被收入研究一的研究为使用中药或中药结合克罗米芬并以西药克罗米芬治疗PCOS为对照的临床实验及临床系列研究,治疗周期为至少三个月或三个月经周期,治愈标准为患者怀孕或获得有证据排卵。利用Mantel-Haenszel方法对38个临床试验(病人总数为2883人)的Meta分析表明中药加克罗米芬的治愈率为60.39%(927/1535)而单用克罗米芬的治愈率为34.57%(466/1348)。结果表明中药结合西药治疗PCOS显著提高了治愈率[OR=3.01(95%CI=2.57/3.52),p=0.00]。倒漏斗图形不对称表明发表偏倚存在(α=2.05,95% CI=0.10/3.99,p=0.04)。研究发现,克罗米芬对PCOS的疗效可以通过结合中药的使用得到显著提高。考虑到发表偏倚的存在,本研究所得结论有待更多临床随机对照实验进一步检验。文献研究二是通过文献数据库的建立和分析来研究中药在治疗PCOS时的用药规律、常用方法、以及不同中药的临床治疗效果。文献检索使用了www.cnki.net, www.ilib.cn和PUBMED。检索年代为1984年到2009。关键词为“多囊卵巢综合征(PCOS)"、“中药”、“数据挖掘(data-mining)"、和“文献数据分析(literature data analysis)。重要相关文献的参考文献使用手工检索。被收入研究二的研究为使用中药或中药结合西药治疗PCOS的临床实验及临床系列研究,治疗周期为至少三个月或三个月经周期；治疗标准为患者怀孕或获得有证据排卵。用来收集和管理数据的软件是微软SQL和微软Excel。中药的功效和类别以英文教科书《中药学》(Materia Medica)为参考,将中药治疗PCOS的相关数据包括中药的使用、治疗方法及治疗结果等输入数据库。通过数据排序和数据挖掘找出与高治愈率最相关的常用中药。在研究二所收集的125篇相关文献中,共有8150位PCOS病人分别接受了中药、中药结合西药、或西药(作为对照)的治疗。所使用的中药分别来自30个类别,共179味。本研究发现,当中药单独使用时或当中药与克罗米芬结合使用时,有12味最常用并与高治愈率最相关的中药。这12味中药分别来自7个中药类别,即活血化瘀药中的川芎、丹参、桃仁和红花；补血药中的当归；补阳药中的巴戟天、肉苁蓉、仙茅；补阴药中的女贞子；补气药中的黄芪；辛凉解表药中的柴胡(在此应用了其疏肝解郁的功效)；及温化寒痰药中的制半夏。值得注意的是,在筛选常用有效中药的过程中发现,当单独使用中药治疗PCOS时,在使用时比不使用时治愈率显著提高的中药主要来自活血、补血、补阳、补阴和补气药。当使用中药结合克罗米芬治疗PCOS时,在使用时比不使用治愈率显著提高的中药主要来自补血、补阳、补阴和补气药。此结果表明中药结合克罗米芬治疗PCOS时,克罗米芬可能起到了相当于中药活血药的功效。通过以上研究发现在使用中药治疗PCOS时补肾活血化瘀类药起着重要作用。中药结合克罗米芬显著提高了单用克罗米芬治疗PCOS的疗效。常用并与高治愈率相关的中药主要来自活血补血药、补阳药、补阴药和补气药。由于目前我们对不同中药间及中西药间可能存在的相互影响的复杂生理生化关系认识得尚十分有限,因此本研究的结论有待更多随机对照临床实验进一步检验。更多还原

【Abstract】 Background:Due to the vast array of side effects associated with many western medicines typically prescribed to treat polycystic ovarian syndrome (PCOS), Chinese herbal medicine has been commonly used in China as a less invasive, yet economical approach to treat PCOS or to improve western medicine’s treatment effect. To date the application status and clinical outcome of Chinese herbs in treating PCOS in China has not been systematically examined.Objectives:(1) To study the effects of Chinese medical herbs on PCOS treatment by a systematic review and meta-analysis of the literature published between 1980 and 2008. (2) To exam the application status, treatment strategies and clinical outcomes of Chinese medical herbs in PCOS treatment by establishing and analyzing a relational database that collects information of PCOS treatment using Chinese herbs from clinical trials and case serial studies published between 1984 and 2009.Methods:(1)Clinical trials using Chinese herbs to treat PCOS were retrieved from www. ilib.cn and MEDLINE (1980-2008) using key words of "PCOS", "Chinese herbs", "systemic review of literature", "meta-analysis", "data mining", "integral Chinese and western medicine". All case serial studies and randomized trials using Chinese herbs alone, comparing herbs combined with clomiphene citrate and clomiphene citrate alone were studied. (2)Publications were searched and retrieved from www.cnki.net,www.ilib.cn and PUBMED (1984-2009) using key words of "PCOS", "Chinese herbs", "integral Chinese and western medicine", "data-mining", and "literature data analysis". Reference lists of each primary study were hand-searched. Clinical trials and case serial studies using pregnancy rate or confirmed ovulation as primary outcome measures and with treatment durations of at least three months or three menstrual cycles were selected for the study. Microsoft SQL Server program and Microsoft Excel were used as data collection and database management tools. Functions and action sections of Chinese herbs were entered into the database according to Materia Medica, a comprehensive and recognized Chinese herbal medicine textbook in English. Herbal usage frequency, treatment strategies and associated treatment outcomes were analyzed. Most frequently used herbs that were also associated with higher cure rates were screened by data sorting and data-mining using Microsoft SQL Server program and Microsoft Excel. In both studies, the main outcome measures were pregnancy rates or obtaining regular ovulatory cycles of 4 weeks confirmed by biphasic body temperature or transvaginal sonography and midluteal phase progesterone concentration levels after 3-6 months of treatment.Results:In research (1), Meta-analysis of the 38 trials (2883 patients) using . Mantel-Haenszel method (fixed effect model) showed the cure rate of Clomid Citrate (CC) with herbs was 60.39%(927/1535) and the cure rate of CC alone was 34.57% (466/1348). There was a significant increased probability of cured [OR=3.01 (95% CI=2.57/3.52), p=0.00] in favor of the herbal integrated treatment. The test of funnel plot asymmetry showed that the chance of publication bias existed (α=2.05, 95% CI=0.10/3.99, p=0.04. In research (2), a total of 125 relevant publications, 8150 patients were treated with Chinese herbs alone, with integral Chinese herbs and western medicine, or with western medicine alone as controls. According to traditional Chinese medicine (TCM) pattern differentiation theory, a total of 179 herbs from 30 action sections were used by different practitioners. By analyzing database and performing data mining using Microsoft Association Rules algorithm,12 of the 179 herbs were found to be the most frequently used herbs that were also associated with higher cure rates in treating PCOS. These 12 herbs include Chuan Xiong, Dan Shen, Tao Ren, Hong Hua from herbs that invigorate Blood; Xian Mao, Ba Ji Tian, Rou Cong Rong from herbs that tonify the Yang; Nu Zhen Zi from herbs that tonify the Ying; Dang Gui from herbs that tonify the blood; Huang qi from herbs that tonify the Qi; Chai Hu from Cool and acrid herbs that release the exterior (used to remove Liver qi stagnation); and Zhi Ban Xia from herbs that warm and transform phlegmConclusion:Research (1) found that clomiphene citrate treatment outcome of PCOS patients may be significantly improved by using Chinese herbs. Considering the risk of publication bias, double blind randomized trials are needed to further confirm the above conclusion. Research (2) found that the most frequently used herbs which were also associated with higher cure rates in treating PCOS were mostly from herbs that invigorate and tonify the Blood, herbs that tonify the Yang, the Yin and the Qi. These are preliminary findings that need futher supports by more randomized controlled clinical studies.更多还原