Comparison of Ethinyl-Estradiol Plus Cyproterone Acetate Versus Metformin Effects on Classic Metabolic Cardiovascular Risk Factors in Women with the Polycystic Ovary Syndrome

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 7; pp. 2453 - 2461
• Main Authors: Luque-Ramírez, Manuel, Álvarez-Blasco, Francisco, Botella-Carretero, José I., Martínez-Bermejo, Elena, Lasunción, Miguel A., Escobar-Morreale, Héctor F.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.07.2007; Endocrine Society
• Subjects: 17β-Estradiol; Acetic acid; Administration, Oral; Adult; Androgen Antagonists - administration & dosage; Androgens - blood; Apolipoprotein A; Apolipoprotein A-I; Biological and medical sciences; Blood Glucose - metabolism; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular system; Cyproterone acetate; Cyproterone Acetate - administration & dosage; Drug Combinations; Dyslipidemia; Dyslipidemias - blood; Dyslipidemias - epidemiology; Ethinyl Estradiol - administration & dosage; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose tolerance; High density lipoprotein; Hirsutism; Humans; Hypoglycemic Agents - administration & dosage; Insulin; Insulin Resistance; Lipids - blood; Menstruation; Metabolism; Metformin; Metformin - administration & dosage; Oral contraceptives; Ovaries; Patients; Phospholipids; Polycystic ovary syndrome; Polycystic Ovary Syndrome - blood; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - epidemiology; Risk Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Antineoplastic agent; Ethinylestradiol; Estrogen; Cardiovascular disease; Antihormone; Polycystic ovary; Epidemiology; Vascular disease; Hypoglycemic agent; Biguanides; Cyst; Atherosclerosis; Adult; Female; Benign neoplasm; Woman; Human; Nutrition; Antiandrogen; Female sterility; Metabolic diseases; Acetate; Ovarian hormone; Cyproterone; Female genital diseases; Ovarian diseases; Risk factor; Cardiovascular risk; Metabolic activation; Contraceptive; Metformin; Sex steroid hormone; Endocrinology; Comparative study
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-0282

Context: Oral contraceptives may worsen the metabolic profile of patients with polycystic ovary syndrome (PCOS), favoring the use of insulin sensitizers in these patients. Objective: The aim of the study was to compare the effects of a contraceptive pill on metabolic classic cardiovascular risk factors with those of the insulin sensitizer metformin. Design: We conducted a randomized, parallel, open-label clinical trial. Setting: The study was conducted at an academic hospital. Patients: Thirty-four consecutive PCOS patients were studied. Interventions: Patients were randomized to oral treatment with metformin (850 mg twice daily) or with the Diane35 Diario pill (35 μg of ethinyl-estradiol plus 2 mg of cyproterone acetate) for 24 wk. Main Outcome Measures: Hyperandrogenism, lipid profiles, and indexes of glucose tolerance and insulin sensitivity were measured at baseline and after 12 and 24 wk of treatment. Results: Diane35 Diario resulted in higher reductions in hirsutism score and serum androgen levels compared with metformin. Menstrual regularity was restored in all the patients treated with Diane35 Diario compared with only 50% of those receiving metformin. Plasma apolipoprotein A-I and HDL-phospholipid levels increased with Diane35 Diario, whereas metformin did not induce any change in the lipid profile. On the contrary, the insulin sensitivity index increased with metformin but did not change with Diane35 Diario. No differences in the frequencies of abnormalities of glucose tolerance and dyslipidemia were found between both treatments. Conclusions: Diane35 Diario appears to be superior to metformin for the control of hyperandrogenism and for the restoration of menstrual regularity in PCOS patients, and it is not associated with any clinically relevant worsening in the classic metabolic cardiovascular risk profile of these women.