Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking

Abstract

ObjectiveTo study the blood clotting tests and endothelial function of polycystic ovary syndrome (PCOS) patients and non-hyperandrogenic women, and their changes during PCOS treatment, as a function of the presence of obesity and smoking.DesignCase-control study followed by a randomized clinical trial.MethodsBlood clotting and endothelial function were analyzed in 40 PCOS patients and 20 non-hyperandrogenic women. Thirty-four PCOS women were randomized to an oral contraceptive containing 35 μg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane35Diario) or metformin (850 mg twice daily), monitoring the changes on these parameters during 24 weeks of treatment. The influence of obesity and smoking was also analyzed.ResultsBlood clotting and endothelial function tests were similar among PCOS patients and controls with the exception of a higher platelet count in the former. Obesity increased circulating fibrinogen levels, prothrombin activity and platelet counts, and reduced prothrombin and activated partial thromboplastin times. Smoking increased fibrinogen levels, platelet counts, and prothrombin activity, and reduced prothrombin time, in relation to the larger waist circumference of smokers. Irrespective of the treatment received, PCOS patients showed a decrease in prothrombin time and an increase in prothrombin activity, with a parallel increase in homocysteine levels in metformin users. The activated partial thromboplastin time decreased markedly in the patients treated with Diane35Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers.ConclusionsOral contraceptives and metformin may exert deleterious effects on blood clotting tests of PCOS women, yet the effects of metformin appear to be milder. Because smoking potentiates some of these effects and deteriorates endothelial function, smoking cessation should be promoted in PCOS patients.