中医药治疗多囊卵巢综合征的系统评价
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摘要
研究背景
多囊卵巢综合征(Polycystic ovary syndrome, PCOS)是指由于卵巢卵泡内膜细胞良性增生,引起雄激素生成分泌过多,造成月经紊乱、持续排卵障碍、高雄激素症状、卵巢多囊样变等一系列表现的临床综合征,多在青春期前后发病。临床表现为月经不调、闭经.、不孕、多毛、肥胖,以及双侧卵巢多囊性增大,属于中医学不孕、闭经、症瘕等病证范畴。如何改善PCOS的临床症状,提高受孕率,减少治疗带来的毒副作用,仍然是目前大家关心的问题。目前西医治疗PCOS致不孕患者主要是促排卵。诱发排卵的经典方法是克罗米芬(CC)和绒毛膜促性腺激素(HCG),还有抗雄激素和抗胰岛素治疗,尿促性素(HMG)、FSH制剂、GnRH、卵巢楔形切除术、腹腔镜下卵巢打孔术、体外受精-胚胎移植等治疗方案。但西药治疗存在一定的毒副作用,手术治疗带有一定的风险,其适应症和安全性尚待进一步确认。中医药治疗PCOS有一定的优势,表现在在调整生殖功能和内分泌代谢等方面。其疗效肯定,副作用小,融合了中医药整体调节患者内分泌环境和代谢紊乱的优势,克服了西医治疗的针对单方面或几个病因的治疗。
临床医生需要在文献报道中寻找有力的证据以支持中医药在PCOS治疗中的确切疗效。但中医药的临床研究存在一定的问题,如何从浩如烟海的文献中收集到最有力的证据一直是临床医生需要解决的首要问题。运用循证医学方法评价中医药治疗PCOS的临床研究,能全面、系统地了解中医药治疗PCOS在科研设计、实施过程和疗效评价等方面的现状和存在的问题,以期为进一步提高其临床研究水平、临床用药和文献质量提供参考。本课题利用多种检索手段检索有关中医药治疗PCOS的临床研究,其中以随机对照试验为主。根据国际Cochrane检索对协助网工作手册标准翻阅每篇论文。对临床研究的文献类型进行分类,着重评价随机对照试验(randomized controlled trials, RCT)的研究质量。由两名评阅者对文献进行质量评价,对两评阅者的评价结果进行Kappa检验,检验结果的一致性。参照Jadad评分量表,计算RCT文献的Jadad得分。对RCT中的纳入与排除标准、疗效判定标准、随机法、样本含量、组间均衡性比较、盲法的运用、治疗方法、统计学方法、随访、退出与失访等内容在SPSS 13.0软件进行描述性分析。运用RevMan4.2软件对其中质量比较高的研究结果进行Meta分析。通过文献质量评价与Meta分析,我们能找出中医药治疗PCOS临床研究的优势与不足,较客观地认识中医药在PCOS治疗中的临床应用价值,为针对性地开展高质量的随机对照研究提供理论依据。
目的意义
本系统评价的目的在以循证医学系统分析的方法,评价对中医药治疗痤PCOS的临床疗效和安全性。
研究方法
1.研究对象及纳入标准
以医学期刊发表的有关中医药治疗PCOS的临床研究文献为研究对象。纳入标准：(1)试验采用随机对照设计方案：文章中采用“随机分组”字样；或文章中采用随机数字表、计算机编码、掷骰子、抛硬币、抽签等方法；或文章中表明采用分层随机法、区分随机法分组。(2)诊断标准：西医诊断标准依据权威的国际或国家专业组织如欧洲人类生殖协会和美国生殖医学协会于2003年在鹿特丹联合召开的PCOS研讨会制定的标准,中华妇产科学、妇产科理论与实践载有的诊断标准等。中医诊断标准符合中医有关“不孕”“闭经”等的诊断标准,如《中药新药临床研究指导原则》、《中医病证诊断疗效标准》等。(3)试验选择研究对象为PCOS患者,为住院观察病人。(4)试验组采用的治疗措施为中医药治疗方案：口服汤药(或中药免煎颗粒)、口服中成药、静脉点滴中药制剂、针刺、电针、耳压、推拿、穴位注射、中药熏洗等其中一项或一项以上者。(5)干预措施：比较中医药和其它药物(包括西药和中药)、安慰剂或空白对照治疗PCOS的临床研究。
2.检索策略
检索的数据库包括：中国生物医学文献数据库(CBMWeb)、清华同方系列数据库(CNKI)之中国期刊全文数据库、中文科技期刊数据库一维普资讯网、万方数据库、PubMed医学文献检索服务系统、Cochrane图书馆中Cochrane系统评价数据库(Cochrane Database of Systematic Reviews,DSR)和Cochrane对照试验核心注册数据库(Cochrane Central Register of Controlled Trials, CCRC)。此外还在临床试验报告论文或综述的参考文献中追踪查阅相关文献。以“多囊卵巢”为关键词或题目,以“中医or中药or中医药”为任意字段,以“对照”为任意字段等合并检索。根据各个数据库的特点制定相关的检索策略。
3.方法学评价
按照临床科研设计、衡量、评价(Design, Measurement and Evaluation in Clinical Research, DME)和循证医学的原则,由两名接受过循证医学培训的评价者阅读全文,并按统一的调查表独立进行评阅。如意见不一致,由两作者共同讨论,以求获得一致意见。选择国内多数研究使用的Jadad评分量表结合临床流行病学要求对纳入的临床研究进行质量评价。由两名接受过培训的评价者按Cochrane系统评价手册,根据Jadad评分量表,对纳入的所有RCT文献进行随机化、盲法、随访3部分内容的质量评分。每部分积分按照标准划分为0-2分,总积分为0-5分。若有分歧,通过与第三方共同讨论解决。同时,对其中的纳入与排除标准、疗效判定标准、随机法、样本含量、组间均衡性比较、盲法的运用、治疗方法、统计学方法、随访、退出与失访、结论推导等内容进行描述性分析。
4.统计分析
用Excel 2003建立数据库,进行数据的录入和管理。采用SPSS 13.0软件对两评阅者的评价结果进行Kappa检验,检验结果的一致性。文献质量评价分析主要采用SPSS 13.0软件进行描述性分析。Meta分析应用国际循证医学协作网提供的统计软件Revman4.3对所收集的数据进行统计。
结果
共检索到可能相关的文献591篇。通过阅读摘要,剔除未查到原文和重复的文献,并对文献进行筛选(删除以西医、中西医结合治疗为主导、中医临床证型、护理、并发症、动物实验和细胞组织等研究文献),得符合标准的文献26篇。RCT文献基本呈逐年上升的趋势。26篇文献中没有一篇为多中心研究,均为单中心研究。有基金支持者3篇(11.54%),3篇均为省级课题。对两评价者的Jadad评分进行Kappa检验。Kappa值为0.70,P<0.01,说明评价的一致性较好。RCT有26篇,Jadad量表评分为0分的有3篇,1分20篇,2分的有3篇。
有20篇(76.92%)文献只提到“随机”字样,未描述具体的随机分配及隐匿方法。没有一篇文献提及采用双盲法或单盲法。没有1篇文献明确提出退出、失访的人数,未见ITT分析。纳入与排除标准均提及到的仅有8篇(30.77%)。疗效判定明确的文献有14篇(53.85%)。样本<60例的有6篇(23.08%),≥60例的有20篇(76.92%),以上文献均未说明样本含量估算的依据。只有4篇(15.38%)文献对组间情况进行了较详细的分析或统计学说明。有8篇(30.77%)未提及具体的统计学方法或直接给出了p值,所以无法判断疗效判定指标的统计学方法正确与否。交待药物不良反应的仅有3篇(11.54%)。
本课题荟萃分析了20篇报道中医药与西药对照治疗PCOS有效率的随机对照研究；9篇中医药与西药对照治疗PCOS妊娠率的随机对照试验；Meta-分析表明：中医药有效率、妊娠率明显高于西药组,并根据对照组对照药物不同分为克罗米芬(CC)组、CC+HCG组、二甲双胍组、达英-35组、安体舒通组进行亚组分析,结果中医药组组有效率、妊娠率均高于对照组。2篇报导中医药组与中药复方组对照治疗PCOS有效率的随机对照试验,Meta-分析结果显示：中医药组临床有效率和中药组无统计学差异(P=0.30)。倒漏斗图分布不对称,认为可能存在一定的发表性偏倚。
结论
中医药治疗PCOS是一种有效的方法。但临床随机对照试验的方法学质量较低,存在潜在的发表偏倚,其临床疗效及安全性有待今后随机对照多中心试验加以证实和重新评估。
Background
Polycystic ovary syndrome (Polycystic ovary syndrome, PCOS) is the clnical symptom of excessive secretion of androgen formation, menstrual irregularities, persistent anovulation, hyperandrogenism symptoms and polycystic ovarian changes cauesd by the increase of benign ovarian thecal cells.such Clinical manifestations are menstrual disorders, amenorrhea, Infertility, hirsutism, obesity, and polycystic ovaries increased, belongs to the concepts of Chinese medicine such as "medical infertility", "amenorrhea", "Zhengjia". How to cure the clinical symptoms of PCOS and improve pregnancy rates, reduce side effects caused by treatment, still are a matter of concern. Western treatment of infertility caused by PCOS is ovulation. Classical ovulation induction has methods auch as clomiphene citrate (CC) and human chorionic gonadotropin (HCG), have anti-androgen and anti-insulin treatment, urinary gonadotropin (HMG), FSH preparation, GnRH, ovarian wedge resection, intraperitoneal endoscopic ovarian drilling technique, in vitro fertilization-embryo transplantation therapy. However, Western medicine has some side effect and some operation risks, its indications and safety still have to be further confirmed. Chinese medicine treatment of PCOS has some advantages in these aspects:the adjustment of reproductive functions and areas of Endocrinology and Metabolism. Chinese medicine has integration of the overall regulation in patients with endocrine and metabolic disorders environmental and overcomes the disadvantages of Western treatment.
Clinicians need to find evidence in support of TCM in the treatment of PCOS from the literature. However, There are some problems in the clinical research of TCM. how to collect the most convincing evidence from a broad array of literature is still a primary problem for clinicians to solve.evaluating Chinese medicine treatment for PCOS by evidence-based medicine can provide a comprehensive, systematic understanding of TCM for PCOS in the research design, implementation and efficacy assessment of the status in order to further improve the clinical research level and the application of clinical drugs. This subject search more information about TCM treatment for PCOS in clinical studies, and randomized controlled trials(RCT) are main research objects. According to the criteria manual work of Cochrane, we read each paper. Two reviewers focuse on the evaluation of RCT. We evaluate the quality of the literature according to Jadad rating score, then we use Kappa test to test the consistency of these results. Enrolled and excluded criteria, criteria for assessment of therapeutic effects, methods of randomization, assessment of sample content, comparability of baseline, methods of blinding, therapeutic methods, statistical methods, following-up, drop-out, conclusions derivation etc. in clinical studies are also evaluated. We use SPSS 13.0 to do the descriptive analysis. Also, we use RevMan4.2 to do Meta-analysis. From these analysis, we can find the advantages and disadvantages of TCM treatment for PCOS and have a more objective understanding of TCM for PCOS in order to carry out high-quality randomized controlled study in this area in furture.
Research Purpose
The purpose of this systematic review is to evaluate the clinical efficacy and safety of TCM for PCOS by the analysis method of evidence-based medicine.
Research Methodology
1. Study object and inclusion criteriaal
The research object is the clinical research literature published in the medical journal of Chinese medicine treatment. Inclusion criteria:(1) randomized controlled design:article in a "randomized" words, or article using random number table, computer code, dice, flip a coin, drawing lots or other methods. (2) diagnostic criteria:Western diagnostic criteria based on authoritative international or national professional organizations such as the European Association of Human Reproduction and American Society for Reproductive Medicine in 2003, Chinese gynecology, the theory and practice standards of obstetrics and gynecology and so on. Chinese Medicine diagnostic criterias consistent with the "Infertility" "amenorrhea" and other diagnostic criteria such as "guiding principles of clinical research in Chinese medicine" and so on. (3)Subjects for the PCOS patient selection:patients hospitalized for observation. (4) The experimental group used therapeutic measures for Chinese medicine treatment:oral decoction (or Chinese fried-free particle), oral proprietary Chinese medicine, traditional Chinese medicine preparation intravenously, acupuncture, electroacupuncture, ear pressure, massage, acupuncture point injection, Chinese smoked wash or others.persons wtih one or more of these therapeutic measures are included. (5) interventions: comparison of medicine with other drugs (including Chinese and Western medicines), placebo or control treatment of PCOS in clinical research.
2. Search strategies
The databases include:Chinese Biomedical Literature Database (CBMWeb), Tsinghua Tongfang series database (CNKI) of the China Academic Journal, a VIP Chinese Science and Technology Periodical Database, PubMed, Cochrane Database of Systematic Reviews (DSR) and Cochrane Central Register of Controlled Trials (CCRC). In addition, we read references to track access to relevant literature. The word "ovary" is uesd as a key word or subject, The phrase "Chinese medicine", "Chinese medicine", "Chinese medicine" or "control" is used in any fields. According to the characteristics of each database, we make differernt search strategies.
3. Evaluation of methodology
According to the design, measurement and evaluation in Clinical Research (DME) and the principles of evidence-based medicine, two received training evaluators read the full text and fill in the questionnaire independently. We discuss if we have different views in order to obtain consensus. The quality assessment uses Jadad rating scale combining with clinical epidemiology. Two reviewers give the score according to Cochrane systematic review manual in 3 respects such as randomization, blinding, follow up. Each part has the score of 0-2, and the total points is 0-5. If two reviewers have differences, they should have the discussion with the third party. Meanwhile, Enrolled and excluded criteria, criteria for assessment of therapeutic effects, methods of randomization, assessment of sample content, comparability of baseline, methods of blinding, therapeutic methods, statistical methods, following-up, drop-out, conclusions derivation etc. in clinical studies are also evaluated.
4. Statistical analysis
To establish a database by using Excel 2003 for data input and management. Quality assessment is mainly in the expression of descriptive analysis. We will do meta-analysis by the software of Revman4.3.
Results
We have retrieved a total of 591 potentially relevant documents. By reading the summary, removing the original that does not exist and the duplicate. There are 26 literatures may meet the included standards. RCT basic literature showed an increasing trend. There are no multi-center study. There are 3 researches having A fund supporter (11.54%). The score of Kappa is 0.70, P<0.01, the evaluation shows good agreement. There are 26 RCT, There are 3 researches having a Jadad score of 0,20 researches having a Jadad score of 1,3 researches having a Jadad score of 2.
There are 20 (76.92%) documents referring only to "random" character, not describing specific methods of random allocation and hidden. There are No document referred to double-blind method or single blind method. There are no literature referring the number of lost, No ITT analysis. Inclusion and exclusion criteria are mentioned in only eight (30.77%) researches. There are 14 (53.85%) researches determining the efficacy of treatment. There are 6(23.08%) researches having sample<60 cases and 20 researches (76.92%) having sample≥60 cases. Above literature shows no basis for estimation of sample size. There are 8 (30.77%) researches that does not mention specific statistical methods, so it is impossible to evaluate the correctness of the statistical method. There are only 3 researches(11.54%) that referring the adverse drug reactions.
The subject analysis 26 reports of TCM for PCOS. Meta-analysis showes that: Chinese medicine is efficient, the pregnancy rate of TCM group is significantly higher than that of western medicine group. The control group were divided into clomiphene citrate (CC) group, CC+HCG group, metformin group, thinylestradiol and Cyproterone Acetate Tablets group, spironolactone group.wo analysis the group treated with Chinese herbal compound group, Meta-analysis showes as follows:There are no significant difference (P=0.30) in the clinical effect between TCM group and Chinese herbal compound group. Funnel plot is in asymmetry distribution, so there may be some publication bias.
Conclusion
TCM is the effective treatment for PCOS. However, there is low methodological quality and potential publication biasin in RCT. The clinical efficacy and safety of RCT need to be confirmed and re-evaluation by multi-center randomized controlled trials in the future.
多囊卵巢综合征(Polycystic ovary syndrome, PCOS)是指由于卵巢卵泡内膜细胞良性增生,引起雄激素生成分泌过多,造成月经紊乱、持续排卵障碍、高雄激素症状、卵巢多囊样变等一系列表现的临床综合征,多在青春期前后发病。临床表现为月经不调、闭经.、不孕、多毛、肥胖,以及双侧卵巢多囊性增大,属于中医学不孕、闭经、症瘕等病证范畴。如何改善PCOS的临床症状,提高受孕率,减少治疗带来的毒副作用,仍然是目前大家关心的问题。目前西医治疗PCOS致不孕患者主要是促排卵。诱发排卵的经典方法是克罗米芬(CC)和绒毛膜促性腺激素(HCG),还有抗雄激素和抗胰岛素治疗,尿促性素(HMG)、FSH制剂、GnRH、卵巢楔形切除术、腹腔镜下卵巢打孔术、体外受精-胚胎移植等治疗方案。但西药治疗存在一定的毒副作用,手术治疗带有一定的风险,其适应症和安全性尚待进一步确认。中医药治疗PCOS有一定的优势,表现在在调整生殖功能和内分泌代谢等方面。其疗效肯定,副作用小,融合了中医药整体调节患者内分泌环境和代谢紊乱的优势,克服了西医治疗的针对单方面或几个病因的治疗。
临床医生需要在文献报道中寻找有力的证据以支持中医药在PCOS治疗中的确切疗效。但中医药的临床研究存在一定的问题,如何从浩如烟海的文献中收集到最有力的证据一直是临床医生需要解决的首要问题。运用循证医学方法评价中医药治疗PCOS的临床研究,能全面、系统地了解中医药治疗PCOS在科研设计、实施过程和疗效评价等方面的现状和存在的问题,以期为进一步提高其临床研究水平、临床用药和文献质量提供参考。本课题利用多种检索手段检索有关中医药治疗PCOS的临床研究,其中以随机对照试验为主。根据国际Cochrane检索对协助网工作手册标准翻阅每篇论文。对临床研究的文献类型进行分类,着重评价随机对照试验(randomized controlled trials, RCT)的研究质量。由两名评阅者对文献进行质量评价,对两评阅者的评价结果进行Kappa检验,检验结果的一致性。参照Jadad评分量表,计算RCT文献的Jadad得分。对RCT中的纳入与排除标准、疗效判定标准、随机法、样本含量、组间均衡性比较、盲法的运用、治疗方法、统计学方法、随访、退出与失访等内容在SPSS 13.0软件进行描述性分析。运用RevMan4.2软件对其中质量比较高的研究结果进行Meta分析。通过文献质量评价与Meta分析,我们能找出中医药治疗PCOS临床研究的优势与不足,较客观地认识中医药在PCOS治疗中的临床应用价值,为针对性地开展高质量的随机对照研究提供理论依据。
目的意义
本系统评价的目的在以循证医学系统分析的方法,评价对中医药治疗痤PCOS的临床疗效和安全性。
研究方法
1.研究对象及纳入标准
以医学期刊发表的有关中医药治疗PCOS的临床研究文献为研究对象。纳入标准：(1)试验采用随机对照设计方案：文章中采用“随机分组”字样；或文章中采用随机数字表、计算机编码、掷骰子、抛硬币、抽签等方法；或文章中表明采用分层随机法、区分随机法分组。(2)诊断标准：西医诊断标准依据权威的国际或国家专业组织如欧洲人类生殖协会和美国生殖医学协会于2003年在鹿特丹联合召开的PCOS研讨会制定的标准,中华妇产科学、妇产科理论与实践载有的诊断标准等。中医诊断标准符合中医有关“不孕”“闭经”等的诊断标准,如《中药新药临床研究指导原则》、《中医病证诊断疗效标准》等。(3)试验选择研究对象为PCOS患者,为住院观察病人。(4)试验组采用的治疗措施为中医药治疗方案：口服汤药(或中药免煎颗粒)、口服中成药、静脉点滴中药制剂、针刺、电针、耳压、推拿、穴位注射、中药熏洗等其中一项或一项以上者。(5)干预措施：比较中医药和其它药物(包括西药和中药)、安慰剂或空白对照治疗PCOS的临床研究。
2.检索策略
检索的数据库包括：中国生物医学文献数据库(CBMWeb)、清华同方系列数据库(CNKI)之中国期刊全文数据库、中文科技期刊数据库一维普资讯网、万方数据库、PubMed医学文献检索服务系统、Cochrane图书馆中Cochrane系统评价数据库(Cochrane Database of Systematic Reviews,DSR)和Cochrane对照试验核心注册数据库(Cochrane Central Register of Controlled Trials, CCRC)。此外还在临床试验报告论文或综述的参考文献中追踪查阅相关文献。以“多囊卵巢”为关键词或题目,以“中医or中药or中医药”为任意字段,以“对照”为任意字段等合并检索。根据各个数据库的特点制定相关的检索策略。
3.方法学评价
按照临床科研设计、衡量、评价(Design, Measurement and Evaluation in Clinical Research, DME)和循证医学的原则,由两名接受过循证医学培训的评价者阅读全文,并按统一的调查表独立进行评阅。如意见不一致,由两作者共同讨论,以求获得一致意见。选择国内多数研究使用的Jadad评分量表结合临床流行病学要求对纳入的临床研究进行质量评价。由两名接受过培训的评价者按Cochrane系统评价手册,根据Jadad评分量表,对纳入的所有RCT文献进行随机化、盲法、随访3部分内容的质量评分。每部分积分按照标准划分为0-2分,总积分为0-5分。若有分歧,通过与第三方共同讨论解决。同时,对其中的纳入与排除标准、疗效判定标准、随机法、样本含量、组间均衡性比较、盲法的运用、治疗方法、统计学方法、随访、退出与失访、结论推导等内容进行描述性分析。
4.统计分析
用Excel 2003建立数据库,进行数据的录入和管理。采用SPSS 13.0软件对两评阅者的评价结果进行Kappa检验,检验结果的一致性。文献质量评价分析主要采用SPSS 13.0软件进行描述性分析。Meta分析应用国际循证医学协作网提供的统计软件Revman4.3对所收集的数据进行统计。
结果
共检索到可能相关的文献591篇。通过阅读摘要,剔除未查到原文和重复的文献,并对文献进行筛选(删除以西医、中西医结合治疗为主导、中医临床证型、护理、并发症、动物实验和细胞组织等研究文献),得符合标准的文献26篇。RCT文献基本呈逐年上升的趋势。26篇文献中没有一篇为多中心研究,均为单中心研究。有基金支持者3篇(11.54%),3篇均为省级课题。对两评价者的Jadad评分进行Kappa检验。Kappa值为0.70,P<0.01,说明评价的一致性较好。RCT有26篇,Jadad量表评分为0分的有3篇,1分20篇,2分的有3篇。
有20篇(76.92%)文献只提到“随机”字样,未描述具体的随机分配及隐匿方法。没有一篇文献提及采用双盲法或单盲法。没有1篇文献明确提出退出、失访的人数,未见ITT分析。纳入与排除标准均提及到的仅有8篇(30.77%)。疗效判定明确的文献有14篇(53.85%)。样本<60例的有6篇(23.08%),≥60例的有20篇(76.92%),以上文献均未说明样本含量估算的依据。只有4篇(15.38%)文献对组间情况进行了较详细的分析或统计学说明。有8篇(30.77%)未提及具体的统计学方法或直接给出了p值,所以无法判断疗效判定指标的统计学方法正确与否。交待药物不良反应的仅有3篇(11.54%)。
本课题荟萃分析了20篇报道中医药与西药对照治疗PCOS有效率的随机对照研究；9篇中医药与西药对照治疗PCOS妊娠率的随机对照试验；Meta-分析表明：中医药有效率、妊娠率明显高于西药组,并根据对照组对照药物不同分为克罗米芬(CC)组、CC+HCG组、二甲双胍组、达英-35组、安体舒通组进行亚组分析,结果中医药组组有效率、妊娠率均高于对照组。2篇报导中医药组与中药复方组对照治疗PCOS有效率的随机对照试验,Meta-分析结果显示：中医药组临床有效率和中药组无统计学差异(P=0.30)。倒漏斗图分布不对称,认为可能存在一定的发表性偏倚。
结论
中医药治疗PCOS是一种有效的方法。但临床随机对照试验的方法学质量较低,存在潜在的发表偏倚,其临床疗效及安全性有待今后随机对照多中心试验加以证实和重新评估。
Background
Polycystic ovary syndrome (Polycystic ovary syndrome, PCOS) is the clnical symptom of excessive secretion of androgen formation, menstrual irregularities, persistent anovulation, hyperandrogenism symptoms and polycystic ovarian changes cauesd by the increase of benign ovarian thecal cells.such Clinical manifestations are menstrual disorders, amenorrhea, Infertility, hirsutism, obesity, and polycystic ovaries increased, belongs to the concepts of Chinese medicine such as "medical infertility", "amenorrhea", "Zhengjia". How to cure the clinical symptoms of PCOS and improve pregnancy rates, reduce side effects caused by treatment, still are a matter of concern. Western treatment of infertility caused by PCOS is ovulation. Classical ovulation induction has methods auch as clomiphene citrate (CC) and human chorionic gonadotropin (HCG), have anti-androgen and anti-insulin treatment, urinary gonadotropin (HMG), FSH preparation, GnRH, ovarian wedge resection, intraperitoneal endoscopic ovarian drilling technique, in vitro fertilization-embryo transplantation therapy. However, Western medicine has some side effect and some operation risks, its indications and safety still have to be further confirmed. Chinese medicine treatment of PCOS has some advantages in these aspects:the adjustment of reproductive functions and areas of Endocrinology and Metabolism. Chinese medicine has integration of the overall regulation in patients with endocrine and metabolic disorders environmental and overcomes the disadvantages of Western treatment.
Clinicians need to find evidence in support of TCM in the treatment of PCOS from the literature. However, There are some problems in the clinical research of TCM. how to collect the most convincing evidence from a broad array of literature is still a primary problem for clinicians to solve.evaluating Chinese medicine treatment for PCOS by evidence-based medicine can provide a comprehensive, systematic understanding of TCM for PCOS in the research design, implementation and efficacy assessment of the status in order to further improve the clinical research level and the application of clinical drugs. This subject search more information about TCM treatment for PCOS in clinical studies, and randomized controlled trials(RCT) are main research objects. According to the criteria manual work of Cochrane, we read each paper. Two reviewers focuse on the evaluation of RCT. We evaluate the quality of the literature according to Jadad rating score, then we use Kappa test to test the consistency of these results. Enrolled and excluded criteria, criteria for assessment of therapeutic effects, methods of randomization, assessment of sample content, comparability of baseline, methods of blinding, therapeutic methods, statistical methods, following-up, drop-out, conclusions derivation etc. in clinical studies are also evaluated. We use SPSS 13.0 to do the descriptive analysis. Also, we use RevMan4.2 to do Meta-analysis. From these analysis, we can find the advantages and disadvantages of TCM treatment for PCOS and have a more objective understanding of TCM for PCOS in order to carry out high-quality randomized controlled study in this area in furture.
Research Purpose
The purpose of this systematic review is to evaluate the clinical efficacy and safety of TCM for PCOS by the analysis method of evidence-based medicine.
Research Methodology
1. Study object and inclusion criteriaal
The research object is the clinical research literature published in the medical journal of Chinese medicine treatment. Inclusion criteria:(1) randomized controlled design:article in a "randomized" words, or article using random number table, computer code, dice, flip a coin, drawing lots or other methods. (2) diagnostic criteria:Western diagnostic criteria based on authoritative international or national professional organizations such as the European Association of Human Reproduction and American Society for Reproductive Medicine in 2003, Chinese gynecology, the theory and practice standards of obstetrics and gynecology and so on. Chinese Medicine diagnostic criterias consistent with the "Infertility" "amenorrhea" and other diagnostic criteria such as "guiding principles of clinical research in Chinese medicine" and so on. (3)Subjects for the PCOS patient selection:patients hospitalized for observation. (4) The experimental group used therapeutic measures for Chinese medicine treatment:oral decoction (or Chinese fried-free particle), oral proprietary Chinese medicine, traditional Chinese medicine preparation intravenously, acupuncture, electroacupuncture, ear pressure, massage, acupuncture point injection, Chinese smoked wash or others.persons wtih one or more of these therapeutic measures are included. (5) interventions: comparison of medicine with other drugs (including Chinese and Western medicines), placebo or control treatment of PCOS in clinical research.
2. Search strategies
The databases include:Chinese Biomedical Literature Database (CBMWeb), Tsinghua Tongfang series database (CNKI) of the China Academic Journal, a VIP Chinese Science and Technology Periodical Database, PubMed, Cochrane Database of Systematic Reviews (DSR) and Cochrane Central Register of Controlled Trials (CCRC). In addition, we read references to track access to relevant literature. The word "ovary" is uesd as a key word or subject, The phrase "Chinese medicine", "Chinese medicine", "Chinese medicine" or "control" is used in any fields. According to the characteristics of each database, we make differernt search strategies.
3. Evaluation of methodology
According to the design, measurement and evaluation in Clinical Research (DME) and the principles of evidence-based medicine, two received training evaluators read the full text and fill in the questionnaire independently. We discuss if we have different views in order to obtain consensus. The quality assessment uses Jadad rating scale combining with clinical epidemiology. Two reviewers give the score according to Cochrane systematic review manual in 3 respects such as randomization, blinding, follow up. Each part has the score of 0-2, and the total points is 0-5. If two reviewers have differences, they should have the discussion with the third party. Meanwhile, Enrolled and excluded criteria, criteria for assessment of therapeutic effects, methods of randomization, assessment of sample content, comparability of baseline, methods of blinding, therapeutic methods, statistical methods, following-up, drop-out, conclusions derivation etc. in clinical studies are also evaluated.
4. Statistical analysis
To establish a database by using Excel 2003 for data input and management. Quality assessment is mainly in the expression of descriptive analysis. We will do meta-analysis by the software of Revman4.3.
Results
We have retrieved a total of 591 potentially relevant documents. By reading the summary, removing the original that does not exist and the duplicate. There are 26 literatures may meet the included standards. RCT basic literature showed an increasing trend. There are no multi-center study. There are 3 researches having A fund supporter (11.54%). The score of Kappa is 0.70, P<0.01, the evaluation shows good agreement. There are 26 RCT, There are 3 researches having a Jadad score of 0,20 researches having a Jadad score of 1,3 researches having a Jadad score of 2.
There are 20 (76.92%) documents referring only to "random" character, not describing specific methods of random allocation and hidden. There are No document referred to double-blind method or single blind method. There are no literature referring the number of lost, No ITT analysis. Inclusion and exclusion criteria are mentioned in only eight (30.77%) researches. There are 14 (53.85%) researches determining the efficacy of treatment. There are 6(23.08%) researches having sample<60 cases and 20 researches (76.92%) having sample≥60 cases. Above literature shows no basis for estimation of sample size. There are 8 (30.77%) researches that does not mention specific statistical methods, so it is impossible to evaluate the correctness of the statistical method. There are only 3 researches(11.54%) that referring the adverse drug reactions.
The subject analysis 26 reports of TCM for PCOS. Meta-analysis showes that: Chinese medicine is efficient, the pregnancy rate of TCM group is significantly higher than that of western medicine group. The control group were divided into clomiphene citrate (CC) group, CC+HCG group, metformin group, thinylestradiol and Cyproterone Acetate Tablets group, spironolactone group.wo analysis the group treated with Chinese herbal compound group, Meta-analysis showes as follows:There are no significant difference (P=0.30) in the clinical effect between TCM group and Chinese herbal compound group. Funnel plot is in asymmetry distribution, so there may be some publication bias.
Conclusion
TCM is the effective treatment for PCOS. However, there is low methodological quality and potential publication biasin in RCT. The clinical efficacy and safety of RCT need to be confirmed and re-evaluation by multi-center randomized controlled trials in the future.
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