Study On The Etiology And Therapy Of Polycystic Ovary Syndrome

Background Polycystic ovary syndrome(PCOS)is a common complex endocrine disorder affecting women in their reproductive years,which is charactered as amenorrhea, infertility,obese,hirsutism,which also has insulin resistance,hyperinsulinemia,and hyperlipidemia.It is one of the metabolic disorder syndrome.Its etiology is still unclear, since the syndrome is strongly familial,there is an evidence to support a major genetic basis for PCOS.Many genes have been indicated to have correalation with PCOS,such as insulin gene,adiponectin gene et al.The complex biochemical characteristics may caused by several genes at the same time.Ghrelin is one head- peptide comprising 28 amino,founded by Kojima in Japan in 1999.It is the endogenous ligrand growth hormone secretagogues receptor(GHSR),which has many kinds of biology effects besides stimulating growth hormone secreat,such as stimulates food intake,and control energy balance,other functions such as stimulating PRL and ACTH releasing,affecting the LH releasing of mankind and the testi of mouse have been reported,it may straightly inhibits LH and T secreating.It is also known to play an important role in beta-cell function and in glucose metabolism,it has correalation with obese and type 2 dibetes.As one kind of Metabolism Syndrome,PCOS has metabolic disorder.Whether ghrelin has effection in the developing of PCOS is unknown.Different polymorphisms of the gene have been researched and have been demonstrated that some polymorphism is associated with obese and 2 type diabetes.Changes of the serum level of ghrelin in PCOS women have been reported.As far as we known,this is the first study dectecting the serum level of ghrelin and exploring the distribution of the three polymorphism rs26802,rs27647, rs2075356 in PCOS women and controls,from our research we expect to dectect the effection of ghrelin in the developing of PCOS.Objectives①To explore the relationship of ghrelin and hormone,insulin,IR and other clinical paramaters by dectecting the serum level of ghrelin,at the same time analyze the significance of serum ghrelin levels in PCOS.②To investigate the distribution of the three single nucleotide polymorphism of ghrelin gene in PCOS patients and controls in a Chinese population and to analysis the association of three single nucleotide polymorphisms in ghrelin gene with the clinical,the hormone and metabolic characteristics and the serum level of ghrelin of PCOS,evalucate genetic influence of the three SNPs of ghrelin gene in development of PCOS.Methods 48 patients with PCOS were recruited according to the revised diagnostic criteria,announced in the 2003 American Society for Reproductive Medicine/European Society for Human Reproduction and Embryology Rotterdam consensus.40 women were selected as healthy controls at the same time.PCOS and controls were both classified as obese group and non-obese group,IR group and non-IR group.The serum ghrelin level, clinical,hormone and metabolism diameters were detected in all subjects,and BMI, WHR,HOMA-IR,HOMA-IS,ISI were calculated.285 patients with PCOS including the 48 patients selected in the first time were recruited according the same criteria.260 women were selected as healthy controls including the 40 controls selected in the first time at the same time.The clinical,hormone and metabolism diameters were detected in all subjects,and BMI,WHR,HOMA-IR,HOMA-IS,ISI were calculated as before.DNA were extracted from human leukocyte nuclei isolated from whole blood.All PCOS and controls were genetyped for three SNPS,two SNP-rs26802 and rs27647,by PCR-RFLP method,and then visualized on a ethidium bromide stained agarose gels,another SNP rs2075356 by Allele-Specific PCR(AS-PCR)of the ghrelin gene.Results①The serum levels of ghrelin were found to be significantly decreased in women with PCOS.The same results were found in obese PCOS women compared to non-obese PCOS women,in obese controls compared to non-obese controls,in non-obese PCOS women compared to non-obese controls,in all IR women compared to non-IR women.Ghrelin levels correalated inversely with BMI,WHR,FINS,HOMA-IR, HOMA-IS,positively with ISI,but no correlation was found between serum ghrelin level and hormone,lipids.After adjusted by BMI,Ghrelin levels correlated inversely with FINS,HOMA-IR,correlated positively with ISI.②No significant differences between the distributions of the three SNPS polymorphisms were observed when PCOS women and the control women were compared.The SNPs rs27647 and rs2075356 had no impact on clinical,hormone,serum ghrelin level and metabolism characteristics of PCOS women.There was no significant difference of hormone,serum ghrelin level,glucose metabolism characteristics of different gene type of the SNP rs26802 in PCOS women, but the PCOS women with AA and AC gene type of ghrelin have higher BMI and WHR compared to that of CC gene type,when AA and AC were combined,the same results were also founded.Conclusions①Hypoghrelinnemia is evident in PCOS,and ghrelin levels correalated inversely with BMI,WHR and IR,but have no correalation with hormone and lipids.②There were no association of SNP rs27647,rs2075356 with clinical,hormone,metabolism characteristics in PCOS women,but SNP rs 26802 was found to be associated with BMI and WHR in PCOS women.③The serum ghrelin level have no correlation with SNP rs27647,rs26802,rs2075356.④The lower ghrelin level may result in the obese and insulin resistance of PCOS,then PCOS women with lower serum ghrelin level should be given therapy of improve metablic,avoiding type 2 diabetes in the future. Background Polycystic ovary syndrome(PCOS)is a common complex endocrine disorder affecting women in their reproductive years,which is character as amenorrhea, infertility,obese,hirsutism.The therapy mainly is incitiving ovulation,clomiphene is the pharmaceutics chich is often firstly choiced.But many PCOS women defeated by clomiphene,FSH and LH may be choiced then,yet both of them will result in OHSS,and the money will be high using them.Ultrasound-guided follicle puncture technique has been used to PCOS.Recently it is recognized that PCOS women have IR,metformin have been used to PCOS.It is still not be reported that ultrasound-guided follicle puncture technique with metformin together can be used to PCOS women.Objectives To investigate the influence of ultrasound-guided follicle puncture technique and with or without Metforrin on polycystic ovarian syndrome(PCOS)in women defeated by Clomiphene.Ovulating rate(OR),pregnancy rate and insulin resistance(HOMA-IR)and HOMA-IS were mainly investigated.Methods PCOS women were random divided into two groups,one group was only given ultrasound-guided follicle puncture technique,the other group was given ultrasound-guided follicle puncture technique and metformin therapy for one month. Ovulating rate(OR),pregnancy rate and HOMA-IR,HOMA-IS were investigated after therapy.Results We found that the ovulating rate was increased,P＜0.01,but there were not changes about HOMA-IR and HOMA-IS in only follicle puncture women.However in both therapy women,not only the OR and HOMA-IS increased,P＜0.01,P＜0.05,but HOMA-IR decreased,P＜0.05.After therapy there was no difference of the ovulating rate between the two groups.But HOMA-IR was lower and HOMA-IS were higher of both therapy group women than the other group women.Pregnancy rate of three months after therapy was higher in both therapy women(39%)than in only follicle puncture women (24%),P＜0.05.Conclusion Women using Metformin with ultrasound-guided puncture technique have good effect on the function of islet and pregnancy rate.