| PCOS (polycystic ovarian syndrome) is one of the most common endocrinological disorders during reproductive age. Studies show PCOS patients not only have endocrine and reproductive dysfunction, but also have metabolic disorders. It is the main reason for infertility in women. IR (Insulin resistance) and hyperinsulinemia are the central links in the pathophysiology of PCOS.It has been reported that mechanism of PCOS-IR is characterized by a receptor postbinding failure. Recent studies suggest that inflammatory factors may play a role in the occurrence of IR. TNF-?(tumor necrosis factor-?) can cause IR by inhibiting insulin receptor tyrosine phosphorylation. The relationship between IR and TNF-?are increasingly concerned by people.People began using insulin sensitizers to treat PCOS-IR. Metformin is the most commonly used drug. Metformin can reduce body weight, insulin and androgen levels, improve menstrual cycle and induce ovulation. As for non-obese patients, it is still controversial on treating with metformin. Some scholars believe that both obese and non obese patients are IR and higher insulin levels with their age and weight matched control group. But obese exacerbate IR, non-obese patients have intrinsic IR.In view of this, people began to treat non-obese PCOS patients with metformin, but the results varied. Some studies have shown that non-obese PCOS patients with metformin treatment are effectiveness, but some studies suggested ineffective. How are about the efficacy of metformin in obese and non-obese patients and whether TNF-?correlating with PCOS-IR are worth further exploration.For the infertility, the main treatment is to induce ovulation, but there is a high ovulation rate and the problem of low pregnancy rate, suggesting that PCOS metabolic abnormalities may affect the metabolism and function of the endometrium. causing defects in endometrial receptivity, embryo implantation dysfunction, resulting in lower pregnancy rate. Differentiation and maturation of endometrial cell require an adequate amount of glucose metabolism. The GLUT4(glucose transporter protein-4) is the carrier of the insulin-mediated glucose transport. The reduction of the glucose transporter protein in endometrium of PCOS patients may be the reason of impaired cell metabolism.Metformin can reduce high blood insulin and improve insulin sensitivity in PCOS patients. However, whether metformin can improve PCOS patients with endometrial IR and have the abnormal GLUT4 expression. The problems of what's the relationship between IR and GLUT4 expression and how does metformin effect the expression of GLUT4 to improve endometrial insulin sensitive are still having no clear explanation at present. Therefore, we need to further study in order to provide a new the theoretical basis for clinical treatment.Part?:Efficacy of Metformin in GLUT4 in endometriun of PCOS patientsObjective:To study the expression of GLUT4 in the endometrium of PCOS patients and the relationship with IR, clarify the efficacy of metformin on the expression of GLUT4 in the endometrium.Methods:We enrolled 20 obses patients diagnosed PCOS with IR(PCOS group),20 obses non-PCOS patients with infertility caused by tubal or pelvic factors (control group). assayed the serum FSH (follicle stimulating hormone), LH(luteinizing hormone), E2 (estradiol-2), T (testosterone), FSG (fasting serum glucose), FINS(fasting insulin serum), ISI (insulin sensitivity index). Endometrial GLUT4, INS (insulin), INS-R (insulin-receptor) protein and GLUT4mRNA, INSmRNA, INS-RmRNA expression were measured by immunohistochemical and RT-PCR(reverse transcription polymerase chain reaction) respectively. These parameters were determined before and after oral administration of metfomin 500mg three times daily for three months in PCOS patients.Results:The levels of serum T, FINS were significantly higher in PCOS group than those in control group (P<0.01), while ISI level was lower in PCOS group than that in control group (P<0.01). There were expressions of GLUT4, INS, INS-R protein and GLUT4mRNA, INSmRNA, INS-R mRNA in endometrium of both two groups. The expression levels of GLUT4 protein and GLUT4mRNA in PCOS patients were significantly lower (P<0.01), INS protein and INS mRNA were significantly higher(P<0.01) than those in control group. The expression levels of INS-R protein and INS-R mRNA were similar in two groups (P>0.05). The expression levels of GLUT4 and GLUT4mRNA in endometrium had a positive correlation with ISI (p<0.01). After three months of treatment, a significant increasing occurred in GLUT4 protein and GLUT4mRNA expressions and a significant reduction occurred in INS protein and mRNA expressions in PCOS patients(P<0.01). There were no changes in INS-R protein and INS-R mRNA expression in PCOS patients (P>0.05).Conclusion:There were expressions of GLUT4 and GLUT4mRNA in endometrial epithelial cells of PCOS patients. But the levels of expression were significantly lower than normal patients. PCOS patients had endometrial IR. The expression levels of GLUT4 and GLUT4mRNA in endometrium had a positive correlation with ISI. Metformin therapy could upregulate the expression level of endometrial GLUT4 to improve the status of the endometrial IR in PCOS patients. Part?:Efficacy of Metformin in serum TNF-?levels, endocrine and metabolic festures of PCOS patientsObjectives:The aim of our study was to assess the serum TNF-?levels, endocrine and metabolic festures of obese and non-obese polycystic ovary syndrome (PCOS) patients and the effects of metformin therapy.Methods:Forty-four diagnosed PCOS patients were recruited. The clinical signs, serum TNF-?levels, endocrine and metabolic parameters were determined before and after oral administration of metfomin 500mg three times daily for three months.Results:The levels of TNF-?, FINS, IAUC were significantly higher in obese group than those in non-obese group (P<0.01), while LH and ISI levels were higher in non-obese group than those in obese group (P<0.01). TNF-?had a positive correlation with BMI (P< 0.01), and had a negative correlation with ISI (P< 0.01). After three months of treatment, in obese women, a significant reduction occurred in BMI, WHR, TNF-?, LH, T, FINS, IAUC, TG, TCH, LDL-c, ApoB(P<0.05?P<0.01). A significant increasing occurred in ISI (P<0.05). In non-obese women, a significant reduction occurred in WHR, TNF-?, LH, T, FINS, IAUC, ApoB(P<0.05?P<0.01) and ISI increased significantly (P< 0.05). Clinical signs were improved in both two group. Ovulation rate was 52.17% in obese group and 52.63% in non-obese group.Conclusion:There were different endocrine characteristics between obese and non-obese PCOS patients. Non-obese PCOS patients showed mainly elevated levels of LH. Obese PCOS patients showed mainly elevated insulin level and decreased ISI. The level of TNF-?was significantly higher in obese group than that in non-obese group. TNF-?might be involved in the occurrence of PCOS-IR. Three months of metformin therapy improved in clinical signs, reduced the levels of TNF-?, LH, T, improved insulin sensitivity in both two groups. Metformin therapy was effective in both obese and non-obese PCOS patients, especially for obese patients. |
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