| Objective:Abnormal uterine bleeding-ovulatory dysfunction(AUB-O)is a common clinical gynecological disease,which seriously affects women’s reproductive health and quality of life.Based on the project "Clinical Application Guidelines on Chinese Patent Medicine in the treatment for abnormal uterine bleeding-ovulatory dysfunction " of China Association of traditional Chinese medicine,using the method of meta analysis,this paper systematically evaluates the efficacy and safety of Chinese patent medicine in the treatment of AUB-O,aiming to select Chinese patent medicine with clear clinical Clear positioning,definite curative effect and evidence-based,which can provide evidence-based support for the treatment of AUB-O with Chinese patent medicine.Methods:1.Identify clinical issuesThrough the expert questionnaire method,collect the clinical problems that need to be solved most in the treatment of AUB-O by Chinese patent medicine,sort out and summarize the collected problems,combine with the research purpose,carry out the structural analysis with PICO mode(Patients,Interventions,Comparisons,Outcomes),and form the important clinical problems to be solved in the project research through the discussion of the expert group.2.Literature search,screening and bias risk assessmentBased on the concept of evidence-based medicine,the retrieval strategy was formulated,and relevant literature was fully retrieved through 3 English and 4 Chinese databases.According to the inclusion and exclusion criteria,the literature was selected to determine the research meeting the requirements of the project.Using the literature bias risk assessment method developed by Cochrane Handbook,the bias risk assessment was carried out for different research types of literature.3.Chinese patent medicine screeningBased on the authoritative information websites such as the official website of the State Food and drug administration,pubiao.com,yaozhi.com and dingxiangyuan.com,and in combination with the national essential medical insurance,industrial injury insurance and maternity insurance drug catalogue in 2019 and the Pharmacopoeia of the people’s Republic of China in 2015,Chinese patent medicine with AUB-O(formerly known as dysfunctional uterine bleeding),metrorrhagia,premenstrual,menorrhagia,prolonged menstruation,and interphase hemorrhage as indication in the specification,were investigated on the above website again.4.Document extraction and evidence comprehensive analysisRead the full text of the literature,extract the relevant materials included in the study,and carry out qualitative or quantitative research on efficacy indicators.The software Revman 5.3 was used to test the heterogeneity,subgroup treatment or sensitivity analysis of RCTs with the same interventions and outcome indicators,and the combined effect amount was calculated.For the more than 10 included studies,the bias was published through funnel chart evaluation,and the final evaluation results were explained and discussed reasonably.Result:1.Results of clinical problem constructionThe research group conducted a questionnaire survey on 12 Chinese and Western gynaecologists in China by formulating a questionnaire on the advantages,efficacy evaluation indicators,adverse reactions and other related clinical problems of Chinese patent medicine in the treatment of AUB-O.Around the research direction of the project,12 questionnaires were collected and summarized to form 5 important clinical problems to be solved in this study.2.Results of literature search,screening and bias risk assessmentTwo people searched the literature back-to-back,and the retrieval time was from the establishment of the database to December 2019.A total of12663 literatures about the treatment of AUB-O were obtained(CNKI 3618,Wanfang 1958,CBM 5615,VIP 1291,MEDLINE 65,EMBASE 96,Cochrane Library 16,4 unpublished clinical studies),3769 duplicate literatures were deleted after duplicate check,and the total number of literatures was 8894,6932 were excluded after reading the title and abstract,and 1962 literatures needed to be read in full were obtained.According to the National Essential Drug Catalogue in 2018,the Pharmacopoeia of the people’s Republic of China in 2015,the national essential medical insurance,industrial injury insurance and maternity insurance drug catalogue in 2019,and the name of Chinese patent medicine obtained through electronic search,it will be researched.In strict accordance with the criteria of literature inclusion and exclusion,134 papers were finally included: 1 meta-analysis,AMSTAR score is 7,medium-quality literature;133 RCT studies,99 rob assessments,10 low-risk,24 uncertain risks.3.Screening results of Chinese patent medicine32 kinds of Chinese patent medicines for treating AUB-O with evidence-based support are included.Referring to Guide for diagnosis and treatment of Common diseases of gynecology in traditional Chinese Medicine in 2012,Guide for clinical application of Chinese patent medicine ×gynaecological diseases fascicle,literature report and drug composition of Chinese patent medicine,Chinese patent medicine for syndrome differentiation and treatment of AUB-O is divided into 7 syndromes:(1)16kinds of blood stasis syndromes: Fuke Yangrong capsule,Yigong granule,Gongxueting granule and Buxue Yimu granule,Nujin tablet,Kunning oral liquid,yixue’an granule,Zhikang Capsule,Luohua Zizhu granule,Fukang tablet,motherwort preparation,Yunnan Baiyao capsule,Duyiwei Capsule,Yunnan Hongyao capsule,Sanqi xueshangning capsule,fuxue’an tablet;(2)5kinds of spleen deficiency syndrome: Gonghuan Yangxue granule,Guipi pill,Bazhen Yimu pill,Fuke Baifeng granule,Yifu Zhixue pill;(3)3 kinds of excess heat syndrome: Gongxuening Capsule,Danzhi Xiaoyao Pill and Fuke duanhongyin capsule;(4)2 kinds of deficiency heat syndrome: Baogong Zhixue granule and Ankun granule;(5)3 kinds of kidney yang deficiency syndrome: Fuke Zaizai capsule,Kunling pill and Peikun pill;(6)2 kinds of kidney yin deficiency syndrome: Fuke zhixueling tablet and Dingkun pill;(7)1 kind of blood deficiency qi stagnation syndrome: Yikunning granule.4.Comprehensive analysis results of evidenceBased on the meta analysis of 11 Chinese patent medicines supported by evidence,most of the heterogeneity tests are within the acceptable range,and a few of them have moderate or severe heterogeneity.The outcome indicators of Meta-analysis study included clinical total effective rate,controlled bleeding time,hemoglobin,estrogen level,endometrial thickness,TCM syndrome score and TCM syndrome efficacy.The results of meta analysis showed that the combination of traditional Chinese medicine and Western medicine was better than that of pure western medicine in the treatment of AUB-O:(1)In the aspect of clinical total effective rate,the combined effect of 11 kinds of traditional Chinese medicine was statistically significant,the heterogeneity between the studies was within the acceptable range,and the combination group was better than the western medicine group;(2)In the aspect of controlling the bleeding time,Gongxuening Capsule,Baogong Zhixue granule,Guipi pill and Zhikang The combined effect of capsule,Kunning oral liquid and Yigong granule is statistically significant.The results of the study support the combined group,but there is moderate or severe heterogeneity between the studies;(3)In improving hemoglobin,the meta analysis results of Gongxuening Capsule,Fuke Yangrong capsule,Gonghuan Yangxue granule,Fuke zaizao capsule and Kunning oral liquid and the qualitative analysis results of Fuke zaizao capsule are all significant.The results showed that the effect of the combination group was better,but there was moderate or severe heterogeneity among the studies except Fuke Yangrong capsule;(4)In terms of reducing estrogen,the other 10 Chinese patent medicine combination groups were better except Yigong granules,and the heterogeneity test showed that only the heterogeneity of Gonghuan Yangxue granules was within the acceptable range;(5)In terms of improving endometrial thickness,Gongxuening Capsule,Baogong Zhixue capsule,Gonghuan Yangxue granule,Nujin tablet,Guipi pill,Zhikang Capsule and Fuke Zhixueling tablet has better effect,but there is heterogeneity among the studies;(6)In improving the syndrome integral of traditional Chinese medicine,the qualitative analysis results show that the combination group of Gongxuening Capsule,Baogong Zhixue Granule and Guipi pill has better effect;(7)In improving the syndrome effect of traditional Chinese medicine,The qualitative analysis of Yigong pill showed that the effect of the combination group was better.The meta analysis results of Gonghuan Yangxue granules showed that the combined effect of Gonghuan Yangxue granules was statistically significant,better than other Chinese patent medicines,and there was basically no heterogeneity between the studies;(8)Chinese patent medicine alone or combined with western medicine in the treatment of AUB-O,the overall tolerance of patients is good,the incidence of adverse events is lower than western medicine alone.The results showed that the total clinical effective rate of Fuke Yangrong capsule,Baogong Zhixue granule,Gonghuan Yangxue granule and Zhikang Capsule was better than that of Western medicine group,and Fuke Yangrong capsule was better than hormone in improving hemoglobin,the difference is statistically significant.The funnel chart was made for 4 kinds of Chinese patent medicines included in more than 10 studies.The results showed that: the possibility of publication bias of Gongxuening Capsule and Fuke Yangrong capsule was small,and Baogong Zhixue granules and Gonghuan Rangxue granules had certain publication bias.Conclusion:1.A total of 32 kinds of Chinese patent medicines for treating AUB-O were obtained through literature study.According to qualitative description or meta analysis,Chinese patent medicine alone or in combination with western medicine can improve symptoms such as excessive menstruation and long bleeding time in patients with AUB-O,and improve the total clinical efficiency.2.Chinese patent medicine combined with hormone therapy is more effective in shorten hemostasis time,reduce estrogen level,improve endometrial thickness,improve the curative effect of TCM syndrome and anemia symptoms of patients with long-term hemorrhage than simple therapy hormone therapy.3.Chinese patent medicine alone or combined with western medicine in the treatment of AUB-O,the overall tolerance of patients is good,the incidence of adverse events is lower than that of Western medicine alone,and the clinical safety is high,which provides evidence-based basis for the safe use of Chinese patent medicine.Due to the factors of small sample size,low quality of methodology,some therapeutic indexes are difficult to solve heterogeneity.The conclusions need to be further verified by more large-scale randomized double-blind control studies. |
