title: Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome.
abstract: BACKGROUND
  This paper is a systematic review of metformin versus clomiphene citrate (CC) in women with polycystic ovary syndrome (PCOS).
  
  
  METHODS
  Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and QUality Of Reporting Of Meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search was done of seven bibliographic databases. Inclusion criteria included cohort and randomized controlled trials (RCT) of women with PCOS and the following medications: metformin versus placebo; metformin versus CC; metformin plus CC versus placebo plus CC. Rev-man 4.1 and Metaview 4.0 were used to analyse data. Relative risk (RR) estimates were presented. A chi2-test determined the significance of the association. Heterogeneity was determined by the Cochran Q-test.
  
  
  RESULTS
  Metformin was 50% better than placebo for ovulation induction in infertile PCOS patients [RR 1.50; 95% confidence interval (CI) 1.13, 1.99]. Metformin was also of benefit in non-infertile (i.e. patients with PCOS who were not complaining of infertility) PCOS patients for cycle regulation compared to placebo (RR 1.45; CI 1.11, 1.90). Metformin was not of confirmed benefit versus placebo for achievement of pregnancy (RR 1.07; CI 0.20, 5.74). Metformin plus CC may be 3-4-fold superior to CC alone for ovulation induction (RR 3.04; CI 1.77, 5.24) and pregnancy (RR 3.65; CI 1.11, 11.99) in women with PCOS.
  
  
  CONCLUSIONS
  Metformin is effective for ovulation induction and cycle regulation in this group of patients. Metformin plus CC appears to be very effective for achievement of pregnancy compared to CC alone. No RCTs directly compare metformin to CC but the need for such a trial exists.
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. skashyap@ottawahospital.on.ca
authors.forename: Sonya
authors.initials: S
authors.lastname: Kashyap
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
mesh_terms: D002996:Clomiphene / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007247:Infertility, Female / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism*; D008687:Metformin / Q000627:therapeutic use*; D010062:Ovulation Induction / Q000379:methods; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic
chemical_list: D005300:Fertility Agents, Female; D007004:Hypoglycemic Agents; D007328:Insulin; D002996:Clomiphene; D008687:Metformin