A Meta-Analysis Determining The Relationship Between Plasma Homocysteine And Insulin Resistance In PCOS

BACKGROUND:PCOS,also known as Stein-Leventhal syndrome,is not only a gynecological disorder,but a sequence of endocrine disorder amongst women in reproductive age,metabolic imbalance such as insulin resistance and dyslipidemia,associated chemical and biochemical hyperandrogenemia that optimally results in psychological disorder.In recent years,both insulin resistance and homocysteine have been the most important features of PCOS.The raised plasma homocysteine have been extensively approved as an absolute risk factor for cardiovascular disease.Both homocysteine and insulin resistance have the ability to induce each other that results in increased level of homocysteine leading to compensatory hyperinsulinemia by inducing insulin resistance.However,metformin has always been the mainstay treatment for PCOS women over the decades;that has shown the effective results.Yet,the association between homocysteine and insulin resistance is still uncertain.OBJECTIVE:The aim of this study is to evaluate the relationship between homocysteine level and insulin resistance in PCOS women and also to assess the behavioral changes in the level of homocysteine and HOMA-IR.METHOD:A systematic search was conducted electronically up to the year 2017 using specific eligibility criteria.Two reviewers completed article search and were entered into the computerized sheet for meta-analysis.Revman 5.3 was used for meta-analysis.All values were extracted as mean±standard deviation(SD).Standardized mean difference(SMD)and the corresponding 95%confidence intervals(95%CI)were used as a measure of effect size.RESULT:In total 6 studies with total number of 440 patients(271 PCOS-IR and 169 PCOS-NIR),women with insulin resistant PCOS and non-insulin resistant PCOS,homocysteine level were significantly lower in non-insulin resistant PCOS(SMD=0.48,95%CI=0.01-0.94,P=0.04;I~2=79%and P=0.0002 for heterogeneity).Another 9 studies with total number of 212 PCOS patients treated with metformin,did not appear to cause any significant change in both the homocysteine levels of PCOS patients(SMD=-0.06,95%CI=-0.74-0.62,P=0.86;I~2=91%,P<0.00001 for heterogeneity)and HOMA-IR(SMD=0.17,95%CI=-0.06-0.40,P=0.15;I~2=46%,P<0.08 for heterogeneity).Different divided subgroups according to the dose of metformin intake,duration of metformin intake and insulin resistant and non-insulin resistant PCOS,post metformin therapy did not cause any significant changes.However,there was significant change in HOMA-IR after metformin therapy when 1700 mg dose of metformin was taken(SMD=0.36,95%CI=0.09-0.63,P=0.010;I~2=0%,P<0.50 for heterogeneity).CONCLUSION:Increased homocysteine levels were observed in PCOS women with non-insulin resistant;therefore,concludes the relationship between homocysteine and insulin resistance in PCOS.However,metformin treatment did not result in any beneficial effect in lowering homocysteine level and HOMA-IR.