title: Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome.
abstract: OBJECTIVE
  To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.
  
  
  METHODS
  A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 microg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated.
  
  
  RESULTS
  After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects.
  
  
  CONCLUSIONS
  Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.
authors.affiliation: Department of Obstetrics and Gynecology, University Magna Graecia of Catanzaro, Catanzaro, Italy. stefanopalomba@tin.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Palomba
authors.forename: Angela
authors.initials: A
authors.lastname: Falbo
authors.forename: Francesco
authors.initials: F
authors.lastname: Giallauria
authors.forename: Tiziana
authors.initials: T
authors.lastname: Russo
authors.forename: Achille
authors.initials: A
authors.lastname: Tolino
authors.forename: Fulvio
authors.initials: F
authors.lastname: Zullo
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Francesco
authors.initials: F
authors.lastname: Orio
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007899:Leisure Activities; D008687:Metformin / Q000627:therapeutic use*; D010919:Placebos; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects; D014805:Vitamin B 12 / Q000097:blood; D049629:Waist-Hip Ratio
chemical_list: D019332:Endothelin-1; D007004:Hypoglycemic Agents; D010919:Placebos; D006710:Homocysteine; D008687:Metformin; D005492:Folic Acid; D014805:Vitamin B 12