Current Situation Of Diagnosis And Management Of Obese Patients With Polycystic Ovary Syndrome And Clinical And Basic Researches Related To Weight-loss Intervention

Part ?:Obesity management in polycystic ovary syndrome:disparity in knowledge between obstetrician-gynecologists and reproductive endocrinologists in ChinaBackground and objective:Approximately 37%of women with polycystic ovary syndrome(PCOS)are obese or overweight in China.Obesity,especially abdominal obesity,is associated with the development of PCOS and contributes substantially to metabolic abnormalities in women with PCOS.Therefore,prompt recognition and management of obesity and related metabolic complications in women with PCOS are crucial.Moreover,several international online surveys have reported differences in practice patterns between gynecologists and reproductive endocrinologists regarding the diagnosis and management of PCOS.This study aimed to describe and compare the practices of physicians in the diagnosis,evaluation,and treatment of obesity in patients with PCOS.Methods:Reproductive endocrinologists(Repro-Endo)and obstetrician-gynecologists(non-reproductive medicine specialty,OB-Gyn)in China participated in this survey,and their responses were analyzed using ?2 tests,Fisher exact tests,and multivariable logistic regression analysis.Results:The study analyzed 1,318 survey responses.(1)General characteristics of the participants:85.8%of the participants were OB-Gyn,and 14.2%were Repro-Endo participants.Most participants were female and above 35 years of age.About 60%of the participants were from tertiary hospitals,and 34.6%were from secondary hospitals.More OB-Gyn participants saw fewer than 50 patients with PCOS per year,and more Repro-Endo participants saw 50-200 patients or more than 200 patients with PCOS per year.(2)Diagnostic criterion for obesity:Body mass index was the most common diagnostic criterion for obesity;only 1.3%of the participants preferred measuring waist circumference to determine abdominal obesity.(3)Assessment of women with obesity and PCOS:42.5%of participants reported ordering both a lipid profile and oral glucose tolerance test(OGTT)for patients with obesity and PCOS.Multivariable analysis,that included physician's specialty,age,hospital grade,and number of patients with PCOS seen annually,revealed that OB-Gyn participants were less likely to order OGTT(OR,0.3;95%CI,0.2-0.4)and lipid profile(OR,0.2;95%CI,0.1-0.3)than Repro-Endo participants.More Repro-Endo participants(25.5%of all participants)enquired about the psychological problems of patients with obesity than OB-Gyn participants.(4)Management of women with obesity and PCOS:The most common treatments for patients with PCOS were lifestyle modification(>95%)and metformin(>80%).The preferred weight loss method for both groups was referred to clinical dietitian,followed by metformin.More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn(47.6%vs.26.3%),and more OB-Gyn participants prescribed metformin at a dose of 1.0 g/day or 0.5 g/day.Only 7.7%of the participants stated they would prescribe glucagon-like peptide-1(GLP-1)receptor agonists for patients with obesity and PCOS for weight loss.Conclusion:Our survey identified knowledge gaps in metabolic screening for patients with obesity and PCOS and a disparity in the evaluation and treatment of obesity in PCOS among different specialties.Similarly,it highlights the need to improve obesity management education for physicians caring for women with PCOS.Part ?:Short-term combined treatment with exenatide once weekly and metformin is superior to metformin alone in reducing weight and improving insulin sensitivity in overweight/obese women with polycystic ovary syndrome:A randomized controlled trialBackground and objective:Obesity and insulin resistance(IR)are common features of polycystic ovary syndrome(PCOS).Metformin increases insulin sensitivity,but it is associated with unsatisfactory weight loss.The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in diabetic patients.This study aimed to explore the therapeutic effects of exenatide once weekly(QW)combined with metformin(MET)on body weight as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Seventy overweight/obese women(BMI?25 Kg/m2)with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups:MET[500 mg three times a day(TID)]or COM(MET 500 mg TID,exenatide 2 mg QW)for 12 weeks.The primary outcomes were anthropometric changes associated with obesity,and the secondary outcomes included changes in reproductive hormone levels,glucose and lipid metabolism,and C-reactive protein.Results:Sixty-one(87%)patients completed the study(30 in MET group,and 31 in COM group).(1)Weight changes:COM therapy was superior to MET monotherapy in reducing weight(P=0.010),BMI(P=0.012),and waist circumference(P=0.049).Patients in the COM group on average lost 3.87±2.72 kg compared with 1.99±2.52 kg in the MET group.In the COM group,BMI and waist circumference decreased by 1.45±1.01 kg/m2 and 3.57±4.20 cm compared with 0.77±0.99 kg/m2 and 1.57±3.37 cm in the MET group,respectively.(2)Testosterone:Serum total testosterone levels were significantly decreased in both COM and MET groups(P=0.003 and P<0.001),but the decrease was similar between the treatments.(3)Glucose metabolism:Levels of fasting glucose and oral glucose tolerance test(OGTT)2-h glucose were significantly lower with COM therapy than with MET(P<0.05).(4)Lipid metabolism and inflammation index:HDL-c,ApoA1,and TG levels increased significantly with both treatments(P<0.01),and no distinct between-treatment differences were found in these parameters.There were no obvious changes in C-reactive protein in two groups before and after the therapy.(5)Adverse events:Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusion:COM therapy was more effective than MET alone in reducing body weight,BMI,and waist circumference,and improving insulin sensitivity in overweight/obese women with PCOS,with acceptable short-term side effects.Exenatide may be a new safe and effective drug for the treatment of overweight/obese women with PCOS,more massive-scale,long-term randomized clinical trials,as well as cost-effectiveness analysis are needed to definitively guide the use of exenatide as a treatment of PCOS.Part ?:Gut Microbiota and exenatide combined with metformin intervention in overweight and obese patients with polycystic ovary syndromeBackground and objective:Studies have shown that gut microbiota dysbiosis was associated with the development of obesity,IR and PCOS.Moreover,it has been reported that liraglutide,a GLP-1 receptor agonist,can reduce weight and improve metabolism by regulating the structure and composition of gut microbiota.In the second part,we have found that exenatide combined with metformin can effectively reduce weight and improve blood glucose in overweight/obese women with PCOS.In this section,we analyzed the gut microbiota of fecal samples from healthy control women,overweight/obese women with PCOS,and PCOS patients after 12 weeks of drug intervention,to explore the correlation between the regulation of gut microbiota and clinical efficacy of exenatide combined with metformin.Methods:In the second part,29 patients in COM group and 25 patients in MET group completed fecal sample collection before and after treatment,and 19 healthy controls with normal weight completed fecal sample collection.Changes in gut microbiota were analyzed by 16S rRNA gene sequencing.Results:(1)The alpha diversity of gut microbiota in overweight/obese women with PCOS was significantly lower than that in healthy controls,but there was no significant difference in beta diversity(PCoA analysis)between the two groups.Species difference analysis showed that,in overweight/obese women with PCOS,the abundance of Firmicutes and its subordinate families and genera increased,while the abundance of Bacteroides and its subordinate families and genera decreased,and Firmicutes/Bacteroides(F/B)ratio increased significantly.Correlation analysis showed that the abundance of gut microbiota related to obesity and abnormal glucose and lipid metabolism increased in overweight/obese women with PCOSs.(2)The Chao index and Shannon index were all alpha-diversity indices.There were no differences in Chao index between and in two groups.Shannon index decreased significantly in COM group,but had no significant change in MET group.The PCoA score plots showed a substantial rearrangement of the microfloral structure in COM group,but not in MET group.At the phylum level,COM therapy significantly decreased the abundance of Firmicutes,Bacteroidetes,and Chloroflexi,and increased the abundance of Actinobacteria,while there was no significant change in community abundance after treatment in MET group.At the genus level,the abundance of Eubacterium_hallii and Bifidobacterium increased,and Bacteroides decreased significantly after treatment in COM group,while only the abundance of Fusicatenibacter decreased significantly after treatment in MET group.There was no significant change in F/B ratio in both treatment groups.Conclusion:Gut microbiota dysbiosis may be involved in the occurrence and development of obesity and metabolic abnormalities in patients with PCOS.Exenatide changed the structure and microbial composition of gut microbiota in overweight and obese patients with PCOS,and the effects of exenatide on gut microbiota were different from metformin.Gut microbiota is a potentially significant component in the mechanism of action of these drugs.