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.
OBJECTIVE
To 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.


METHODS
Case-control study followed by a randomized clinical trial.


METHODS
Blood 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 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35)Diario) 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.


RESULTS
Blood 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 Diane(35)Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers.


CONCLUSIONS
Oral 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.
Luque-Ramírez
Manuel
M
Department of Endocrinology, Hospital Universitario Ramón y Cajal & Universidad de Alcalá, Madrid, Spain.
Mendieta-Azcona
Covandonga
C
del Rey Sánchez
José M
JM
Matíes
Milagro
M
Escobar-Morreale
Héctor F
HF
D000328:Adult; D000726:Androgen Antagonists / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage; D017373:Cyproterone Acetate / Q000008:administration & dosage*; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008687:Metformin / Q000008:administration & dosage*; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010314:Partial Thromboplastin Time; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D011516:Prothrombin / Q000378:metabolism; D012907:Smoking; D055815:Young Adult
D000726:Androgen Antagonists; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D006710:Homocysteine; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; C032640:Cyproterone acetate, ethinyl estradiol drug combination; D011516:Prothrombin; D005340:Fibrinogen; D008687:Metformin