The Efficacy And Safety Of Exenatide Combined With Metformin For Polycystic Ovary Syndrome In Obese Women Of Reproductive Age

Part one The Relationsip between Serum Irisin and PCOS of Reproductive AgeBackground and Objective Polycystic ovary syndrome(PCOS)is one of the most common endocrine metabolic disturbance and reproductive disorder in women of reproductive age,who mainly manifests oligo-ovulation,menstrual disorders,hyperandrogenism and insulin resistance.Until now,the etiology of PCOS is unclear.Hyperinsulinemia and insulin resistance are considered as a critical role in the pathogenesis of PCOS.Recent studies show that adipokine and myokine may play an important role in the development of insulin resistance in PCOS.Irisin is a novel myokine involved in white adipose tissue development of brown adipose tissue,which could speed up metabolism,accelerate energy release,lose weight in human.It is considered as a therapeutic target linked to the obese and related metabolic diseases.It also provides a useful new way for the treatments as well as investigation of etiologies of PCOS.This study aim to investigate the relationship between irisin and the indexes of endocrine and metabolic by comparing serum irisin level in PCOS patiens and women with nomal menstrual while all these people are in childbearing age.To reveal the role of irisin in energy metabolism in PCOS.Methods 180 patients of PCOS in reproductive age from the first affiliated hospital of Zhengzhou University between Jan.2013~Jan.2017 were observed.Choose the 40 women with physical examination and nomal menstrual as normal contral group.Test and compare the fasting plasma glucose(FPG),glycosylated hemoglobin A1C(Hb A1C),fasting insulin(FINS),blood lipid,liver function,thyroid function,follicle stimulating hormone(FSH),sex hormone binding globulin(SHBG),testosterone(T),luteinizing hormone(LH),dehydroepiandrosterone sulfate dehydroepiandrosterone(DHEAS),androstenedione and serum leptin.Insulin resistance index(HOMA-IR)was calculated according to the homeostasis model assessment method.The liver fat content(LFC)was detected by quantitative ultrasound.The percentage of body fat and body fat distribution(LF%,TF%,BF%,A%,G%,A/G)and lean mass were determined by dual energy X-ray absorption method.Statistic analyses were done by SPSS 19.0 software.Results 1.In PCOS patients,the incidence of overweight and obese was 66.7%,hypertension was 5.6%,abnormal lipid metabolism was 20% and DM was 9.4%.2.Compared with the normal control group,the weight?BMI?WHR?2h PG?FINS?2h INS?HOMA-IR?TG?LDL-C?LH/FSH?T?DHEAS?AND?FAI?LF?TF?BF?Android fat%(A)?A/G?VAT?lean mass?LFC and Irisin significantly increased(P<0.01 or P<0.05),while SHBG?HDL-C and Gynoid(G)significantly decreased(P<0.01).BMD and bone metabolism increased(P>0.05).3.In overweight/obese PCOS patients,compared with the normal weight group,the 2h PG?FINS?2h INS?HOMA-IR?LFC?LH/FSH?FAI?TF?BF?A/G?VST ? LFC and Irisin significantly increased(P<0.05),while SHBG and G significantly decreased(P<0.01),VAT?HDL-C?LDL-C?TG were no difference(P>0.05)4.With the increase of BMI,the incidence of abnormal menstruation or ovulation dysfunction,the hyperandrogenism or clinical manifestations and polycystic ovarian increased in PCOS women of reproductive age;5.In PCOS patients,serum Irisin levels were positively correlated with BMI,HOMA-IR?FINS?FAI?lean mass?Android fat%?VAT and body fat%(P<0.05);6.Multiple linear regression analysis showed that HOMA-IR?BMI?FAI?body fat%?Android fat% were the main factors influenced serum irisin.Conclusions The disturbance of glucolipid metabolism and reproductive hormone disorder of PCOS women in reproductive age were dramatically more serious than those in normal control group,the difference was more obvious in the obese PCOS,the reproductive dysfunction were gradually worsen with the increase of BMI.The study showed that a positive correlation exists between serum irisin and HOMA IR,FAI with BMI,body fat rate,Android fat %,which may revealed serum irisin involved in the development of insulin resistance,reproductive disorder and redistribution of body composition.Irisin may be involved in energy metabolism in the occurrence and development of PCOS by regulating a variety of organizations metabolism.Part two The Efficacy and Safety of Exenatide Combined with Metformin for Polycystic Ovary Syndrome in Obese Women of Reproductive AgeBackground and Objective Exenatide(EXA)is a kind of glucagon-like peptide-1(GLP-1)receptor agonists.It can inhibit feeding center of hypothalamus,tamp down appetite,slow gastric emptying so as to decrease feed intake and lose weight.Exenatide is widely used in obese type 2 diabetes,but because the secretion pattern of insulin depend on the level of plasma glucose,the incidence rate of hypoglycemia is rare.Recently GLP-1R agonist and GLP-1 analogue have been used as a therapeutic alternative treatment for obese PCOS,but further study is still needed because of less samples and short treatment time.This study aim to assess the efficacy and safety of Exenatide single or combined with metformin for PCOS in obese women of reproductive age,by comparing irisin,the metabolic parameters and reproductive hormones before and after different course therapy.Methods 1.This study was a randomized controlled trial and was approved by the medical ethics committee of our hospital.All patients fully undestood the study protocols and signed informed consent;2.All PCOS women were 20-40 years old,they had normal glucose tolerance,according to the diagnostic standards of Rotterdam criteria 2003 and BMI?24kg/m2;3.Study groups:MET group : metformin(Glucophage)500mg bid po,addition to 1000 mg bid after 1 weeks EXA group : the Exenatide(Byetta)5ug bid i H,addition to10 ug bid i H,after 4 weeks COM group : metformin combined with the Exenatide,the method is same as above.4.The levels of serum irisin,blood glucose and lipid metabolism,reproductive hormones,ovary volume,menstrual cycle,ovulation rate,pregnancy rate and adverse reaction were observed after treated for 12 weeks and 24 weeks.5.Statistic analyses were done by SPSS 19.0 software.Results 1.A total of 156 cases(86.7%,156/180)completed 12 weeks treatment,including 60 cases of MET group(93.8%,60/64),40 cases of EXA group(77.5%,40/48),56 cases of COM group(82.1%,56/68);a total of 82 patients completed 24 weeks treatment,including 36 cases in MET group,22 cases in EXA group,24 cases in COM group.2.Before treatment,there was no significant difference in baseline data between the three groups(P > 0.05).3.After 12 weeks of treatment,BMI,FINS,HOMA-IR,2h PG and TG were significantly decreased in all groups(P<0.05);serum irisin,DHEAS and LH/FSH decreased(P<0.05);HDL-C,each menstrual frequency was higher than before(P <0.05);In COM group,WHR,T,ALT,LFC and BF decreased(P<0.05),TF and LF had no changes.The three groups has no significant difference in recovery period(P>0.05),but the ovulation rate and pregnancy was obviously higher in COM group than that of MET and EXA group(P < 0.05).4.After 24 weeks treatment,FINS,BMI,WHR,2h PG,HOMA-IR,TG,Irisin,LH/FSH and serum DHEAS level were significantly decreased in all groups(P<0.01 or P<0.05);In COM group,TF,LFC and BF decreased(P<0.05);HDL-C,SHBG,each menstrual frequency higher than before(P<0.05).Ovulation rate and pregnancy rate were obviously higher than that of treatment of 12 weeks in MET group and EXA group(P < 0.05).Ovulation rate and pregnancy in COM group were higher than MET and EXA group,the difference statistically significant(P < 0.05).5.No hypoglycemia happened in the 3 groups.Gastrointestinal reaction was the most common adverse reactions,but all disappeared or reliefed after 2 weeks' treatment.Conclusions 12 weeks treatment with exenatide single or combined with metformin can improve insulin resistance,attenuation glucolipid metabolic disturbance and reproductive disorders via decreasing serum irisin in obese PCOS of reproductive age.COM group was superior to the other treatment groups,especially in increase of ovulation rate and pregnancy rate.Prolong treatment period can led to more clinical benefits.This study have proved safe and effective in the treatment of obese PCOS with exenatide combined with metformin.However,it is still need a larger sample and a longer observation to confirm its feasibility and practicality.