title: Effects of metformin and ethinyl estradiol-cyproterone acetate on clinical, endocrine and metabolic factors in women with polycystic ovary syndrome.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is a major endocrine abnormality that affects women of reproductive age. Oral contraceptive pills are usually the first choice of treatment for PCOS when fertility is not desired. Metformin, an insulin-sensitizing drug, has been shown to improve such metabolic abnormality. Aim. To compare the effects of a contraceptive pill in combination with metformin on the clinical, endocrine and metabolic parameters in obese and non-obese patients with PCOS.
  
  
  METHODS
  Sixty PCOS patients (25 obese, 35 non-obese) were enrolled in this prospective clinical study. PCOS was defined according to the Rotterdam criteria. Patients were randomized to oral treatment with Diane35 (35 microg ethinyl estradiol plus 2 mg cyproterone acetate), metformin or a combination of Diane35/metformin for 3 months. Body mass index (BMI), waist-to-hip ratio (WHR), Ferriman-Gallwey (FG) score, leuteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, fasting insulin and glucose/insulin ratio were measured at baseline and at the end of treatment.
  
  
  RESULTS
  Diane35 resulted in a higher reduction of FG score in both obese and non-obese PCOS patients compared with metformin. Menstrual regularity was restored in all PCOS patients treated with Diane35 compared with only 28% of those receiving metformin. Metformin significantly decreased BMI and WHR in obese patients (p < 0.05). Testosterone levels decreased in all three groups. LH levels and LH/FSH ratio decreased with Diane35 and Diane35/metformin in both obese and non-obese patients. Metformin significantly decreased fasting insulin concentrations (p < 0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese and non-obese PCOS patients, while no significant changes were observed in the Diane35 group. In addition, insulin levels also decreased (p < 0.05) in the Diane35/metformin group.
  
  
  CONCLUSIONS
  Our data show that a combination of metformin and contraceptive pill may be more effective in suppressing the hyperandrogenemia of obese and non-obese PCOS patients than metformin alone and may reduce insulin levels more than contraceptive pill alone. Hence, combined treatment may become a more effective therapeutic option for PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China. jie.wu@yale.edu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage; D017373:Cyproterone Acetate / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005215:Fasting; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008687:Metformin / Q000008:administration & dosage*; D009765:Obesity / Q000150:complications; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood; D049629:Waist-Hip Ratio
chemical_list: D003277:Contraceptives, Oral, Combined; D007328:Insulin; D013739:Testosterone; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin