Epidemiological,Clinical And Basic Study Of Integrated Chinese And Western Medicine In The Treatment Of Polycystic Ovary Syndrome

Part? Epidemiological Study of Integrated Chinese and Western Medicine in the Treatment of Polycystic Ovary SyndromeObjective:Polycystic ovary syndrome(PCOS)is the most common gynecological endocrine disease in women of reproductive age,the main clinical manifestation is reproductive dysfunction,usually accompanied by endocrine and metabolic abnormalities.Traditional Chinese medicine has a long history in treating gynecological diseases and has been widely used in the treatment of chronic metabolic diseases.However,up to now,there is no data about the application of traditional Chinese medicine on polycystic ovary syndrome,especially by Western medicine doctors.Therefore,we carried out a survey on the usage of integrated Chinese and western medicine in treatment of polycystic ovary syndrome among physicians specialized in Obstetrics and Gynecology or Reproductive Medicine in an efford to know about its current application status.Methods:We initiated an online questionnaire survey on the largest training platform of Obstetrics and Gynecology in China.Survey contents:(1)Demographic data.(2)clinical experiences in PCOS treatment.(3)diagnostic criteria used for PCOS.(4)Evaluation of PCOS-related metabolic problems.(5)Western medicine treatment.(6)The application of traditional Chinese medicine in the treatment of PCOS.Statistical methods:descriptive statistical analysis results were showed in the form of frequency and percentage.Descriptive statistics,Chi-square test and multivariate logistic regression statistical analysis were used.Results:A total of 3,213 questionnaires were collected.Questionnaires containing invalid responding were exclued in the statistical analysis.Finally,2328 questionnaires were included in the statistical analysis.(1)Demographic data:Most of the respondents(94.5%)were obstetrician-gynecologists,and 5.5%were reproductive physicians.77.2%of the respondents were 36 years old or above,73.8%of the respondents had more than 10 years of clinical experience,and 86.5%of the respondents came from secondary and tertiary hospitals.(2)Clinical experiences in PCOS treatment:95.2%of the respondents had more than 1 year of experience in the diagnosed and treatment of PCOS,and 53.5%of the respondents had diagnosed and treated PCOS for more than 5 years.69.5%of the respondents saw less than 50 PCOS patients annually,23.0%of the respondents treated 50-200 PCOS patients annually,and 7.6%treated more than 200 PCOS patients annually.Physicians specialized in Reproductive Medicine,treating PCOS for longer years or came from tertiary hospitals saw more PCOS patients annually.(3)Diagnostic criteria used for PCOS:Reproductive physicians,physicians who saw more than 200 PCOS patients annually or came from tertiary hospitals preferred to choose the Rotterdam criteria.Only 1/3 of the respondent could use the diagnostic criteria which they chose correctly.Reproductive physicians,physicians who had more than one year of experience in PCOS treatment or saw more than 200 PCOS patients annually or came from tertiary hospitals were more likely to use the diagnostic criteria correctly.(4)Evaluation PCOS-related metabolic problems:93.9%of the respondents asked family history of diabetes,cardiovascular diseases or PCOS.88.6%of the respondents evaluated glucose tolerance,of which 47.7%would evalute the glucose tolerance for all patients,and 52.3%evaluated the glucose tolerance only for those who were obese.Physician who had treated PCOS for a longer time,saw more PCOS patients annually or came from tertiary hospitals paid more attention to the evaluation of metabolic problems.(5)Western medicine treatment:for patients who had no fertility requirements,oral contraceptives was the most common used method(85.4%),followed by lifestyle adjustment(75.4%)and metformin(53.4%).For patients who had fertility requirements,lifestyle adjustment(90.8%)was the most commonly used method,other commonly used methods were metformin(67.5%),clomiphene(59.5%),letrozole(55.0%).Age,specialty,experience of PCOS treatment,and hospital type were related factors that influenced the application of western medicine.(6)Application of traditional Chinese medicine in the treatment of PCOS:70.4%of the respondents used traditional Chinese medicine in the treatment of PCOS.Physicians who were 56-year-old and above,saw 50-200 PCOS patients annually or came from non-tertiary hospitals were more likely to prescribe traditional Chinese medicine.The top three most commonly used Chinese patent medicines were Dingkun Dan,Qilin Pill and Liuwei Dihuang Pill.Conclusions:Most of the obstetrician-gynecologists and reproductive physicians have insufficient understanding of the diagnostic criteria of PCOS,and the correct application rate of the diagnostic criteria is low.Most respondents evaluate PCOS-related metabolism problems in the clinic,but more than half of the doctors do not conduct the assessments according to the guidelines.For patients without fertility requirement,the application of lifestyle adjustment needs to be emphasized.For patients with fertility requirement,more respondents choose metformin instead of oral ovulation induction drugs recommended by guidelines.Continue education of physicians is needed to improve the quality of medical service for PCOS patients.Traditional Chinese medicine is widely used in the treatment of PCOS.Physicians over 56 years old and saw 50-200 PCOS patients annually or came from non-tertiary hospitals were more likely to prescribe Traditional Chinese medicine.Part ? Clinical Study of Integrated Chinese and Western Medicine in the Treatment of Polycystic Ovary SyndromeObjective:The etiology and mechanism of polycystic ovary syndrome have not been clarified,there is no curative treatment up to now,all the therapeutic methods are symptoms based.The most commonly used drug is oral contraceptive,however,it may impair glucose and lipid metabolism and increase the risk of thrombosis.Traditional Chinese Medicine has been widely used for the treatment of PCOS in China,according to our survey in part I of the essay.The clinical efficacy and fewer side effects of Traditional Chinese Medicine have been reported in some observational trials.Given to these advantages,more and more researchers are interested in the application of Traditional Chinese Medicine for PCOS.The Traditional Chinese Medicine Dingkundan has a long history of treating gynecological diseases and is widely used for the treatment of PCOS,but there is no high quality evidence of its clinical efficacy.In this part,we intends to study the clinical efficacy of Dingkundan alone or in combination with oral contraceptives for the treatment of PCOS.Methods:This was a single-center randomized controlled clinical study.117 of PCOS patients were randomly assigned to three groups:the Chinese medicine Dingkundan group(group A),the Western medicine Diane-35 group(group B),and the combination of Dingkundan and Diane-35 group(group C).Dingkundan was taken orally by 7 g daily,and Diane-35 was taken orally by one tablet daily,both drugs were taken cyclically for twenty-one continuous days followed by seven drug-free days.The treatments was administered for three months.Menstruation cycles,acne and hirsutism scores,sex hormone,2h OGTT and lipid profile were measured.Results:110 patients(94.0%)completed the trial(36 in group A,35 in group B,and 39 in group C).(1)Menstruation:The incidence of regular menstrual cycles in group A was 25%,94.3%in group B,and 87.2%in group C.There were significant differences between group A and group B(P=0.000),group A and group C(P=0.000),and there was no significant difference between group B and group C(P=0.435).(2)Acne and hirsutism scores:After 3 months of treatment,the acne score in each of the three groups were decreased significantly(P<0.001),and the hirsutism score was not significantly changed in each of the three groups(P>0.05).The acne score(P=0.877)and hirsutism scores were not significantly different among the three groups(P=0.255)after three months of treatment.(3)Sex hormones:After 3 months of treatment,total testosterone,DHEAS,LH,LH/FSH in groups B and group C were significantly decreased(P<0.001),and there were no significant changes in group A(P>0.05).(4)Glucose metabolism:After 3 months of treatment,the insulin sensitivity index QUICKI in group A(P=0.0288)and group C(P=0.0350)were significantly increased,and there was no significant change in group B(P=0.902).There was no significant difference of QUICKI among the three groups(P=0.803)after treatment.HOMA-IR was significantly decreased in group C(P=0.04),not significantly changed in group A(P=0.383)or group B(P=0.424),there was no significant difference among the three groups after treatment(P=0.855).The OGTT 2h plasma glucose of each of the three groups had not changed significantly(P>0.05),but there was a significant difference among three groups after treatment(P=0.024),with its level in group A significantly lower than that in group B(P=0.007),there was no significant difference between groups A and C or between groups B and C.(5)Lipid metabolism:Compared with baseline,the changes of lipid profiles within each of the three groups after 3 months of treatment:TC was significantly decreased in group A,not significantly changed in group B,significantly increased in group C;LDL-C in groups A and B were significantly decreased,no significant change was observed in group C;HDL-C was not significant changed in group A,significantly increased in group B,not significantly changed in group C;TG increased significantly in all of the three groups;FFA in group A decreased significantly,but not changed in groups B and C.For the comparison among groups after 3 months of treatment,TC in group A was significantly lower than groups B(P=0.042)and C(P=0.002);HDL-C in group A was significantly lower than groups B(P=0.002)and C(P=0.005);LDL-C was not significantly different among the three groups;TG was also not significantly different among the three groups;FFA in group A was significantly lower than group B(P=0.004),but not significantly different from group C(P=0.147);There were no significant differences of lipid profiles between groups B and C.In a word,group A reduced TC and FFA effectively compared with groups B and C,and there was no difference between the effects of groups B and C on lipid profiles.Conclusions:The Traditional Chinese Medicine Dingkundan can effectively improve the glucose and lipid metabolism of PCOS,but it is not as effective as oral contraceptive Diane-35 in improving the menstrual cycle regularity and hyperandrogenism.The combination of those two medications can effectively regulate menstrual cycles,reduce hyperandrogenism,while improving glucose metabolism,which suggests that the integrative of Chinese medicine and western may be a better option for the treatment of PCOS in the future.Part ? Basic Study of Integrated Chinese and Western Medicine in the treatment of Polycystic Ovary SyndromeObjective:The clinical trial in the second part showed that integrated Chinese and Western medicine can treat PCOS effectively,but currently there is no research on its mechanism.Metabolomics is the study of small molecule metabolites within cells,biofluids,tissues or organisms.Its a branch of systems medicine,which is highly consistent with the holistic concept of traditional Chinese medicine.In this part,we intend to explore the mechanism of integrated Chinese and Western medicine on PCOS through metabolomics study.Methods:Serum samples of 110 patients of the clinical trial in the second part of the essay were analyzed by metabonomics based on high resolution orbitrap mass spectrometry.Results:Our results revealed that Dingkundan,Diane-35 or concomitant therapy did induce dramatic metabolic changes in PCOS patients after treatment.Most metabolites exhibited identical regulation by either Diane-35 or Dingkundan,including elevated levels of amino acids,fatty acid primary amides and various vitamins.Lipid metabolism was differentially regulated by Diane-35 and Dingdundan including phosphatidylcholine biosynthesis,fatty acid unsaturation process.Dingkundan induced reduced levels of phosphatidylcholines and down regulated linoleic acid and linolenic acid.However,Diane-35 moderated the suppression during the drug therapy.In concombination treatment,Diane-35 played dominant function in metabolic regulation.Conclusions:In this study we compared the metabolic regulation of Dingkundan and Diane-35 systematically for PCOS treatment.Conclusively,most metabolites including amino acids,vitamins and hormones were consistently changed by either Dingkundan or Diane-35.However,Dingkundan caused more significant down regulation of fatty acid and phosphatidylcholine metabolism compared to Diane-35,which may be the mechanism of Dingkun Dan in improving metabolic disorders of PCOS patients.