title: Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study.
abstract: Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.
authors.affiliation: Department of Obstetrics and Gynecology, , University Hospital of Oulu, FIN-90014 Oulu, Finland.
authors.forename: Laure
authors.initials: L
authors.lastname: Morin-Papunen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Vauhkonen
authors.forename: Riitta
authors.initials: R
authors.lastname: Koivunen
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Martikainen
authors.forename: Juha S
authors.initials: JS
authors.lastname: Tapanainen
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D017373:Cyproterone Acetate / Q000627:therapeutic use*; D004338:Drug Combinations; D004734:Energy Metabolism / Q000187:drug effects; D045166:Estradiol Congeners / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D010084:Oxidation-Reduction / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D003276:Contraceptives, Oral; D004338:Drug Combinations; D045166:Estradiol Congeners; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007004:Hypoglycemic Agents; D008055:Lipids; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D008687:Metformin