{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T18:46:40Z","timestamp":1773773200495,"version":"3.50.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Case-control study followed by a randomized clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u200a\u03bcg ethinyl-estradiol plus 2\u200amg cyproterone acetate (Diane<jats:sup>35<\/jats:sup>Diario) or metformin (850\u200amg twice daily), monitoring the changes on these parameters during 24 weeks of treatment. The influence of obesity and smoking was also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:sup>35<\/jats:sup>Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-08-0725","type":"journal-article","created":{"date-parts":[[2009,1,13]],"date-time":"2009-01-13T01:13:44Z","timestamp":1231809224000},"page":"469-480","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":45,"title":["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"],"prefix":"10.1093","volume":"160","author":[{"given":"Manuel","family":"Luque-Ram\u00edrez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Covandonga","family":"Mendieta-Azcona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M","family":"del Rey S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milagro","family":"Mat\u00edes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor F","family":"Escobar-Morreale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"3","key":"1_17659330","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1210\/er.2003-0004","volume":"24","author":"Legro","year":"2003","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"4","key":"2_18784319","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1210\/jc.2004-1045","volume":"90","year":"2005","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"7","key":"3_28318784","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1210\/jc.2007-0282","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"12","key":"4_29617011","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1093\/humrep\/dem324","volume":"22","year":"2007","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"11","key":"5_18511417","doi-asserted-by":"publisher","first-page":"5454","DOI":"10.1210\/jc.2003-032237","volume":"89","author":"Talbott","year":"2004","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"8","key":"6_17179260","doi-asserted-by":"publisher","first-page":"3871","DOI":"10.1210\/jc.87.8.3871","volume":"87","author":"Yildiz","year":"2002","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"10","key":"7_11068356","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1161\/01.CIR.103.10.1410","volume":"103","author":"Paradisi","year":"2001","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"issue":"10","key":"8_10559370","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1093\/aje\/152.10.897","volume":"152","author":"Sakkinen","year":"2000","journal-title":"American Journal of Epidemiology","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9262","issn-type":"print"},{"issue":"11","key":"9_16255097","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1172\/JCI118709","volume":"97","author":"Steinberg","year":"1996","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"7","key":"10_29611426","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.tem.2007.07.003","volume":"18","author":"Escobar-Morreale","year":"2007","journal-title":"Trends in endocrinology and metabolism: TEM","ISSN":"https:\/\/id.crossref.org\/issn\/1043-2760","issn-type":"print"},{"issue":"19","key":"11_22792532","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1001\/archinte.166.19.2081","volume":"166","author":"Alvarez-Blasco","year":"2006","journal-title":"Archives of Internal Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0003-9926","issn-type":"print"},{"issue":"8990","key":"12_16117168","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1016\/S0140-6736(95)91928-7","volume":"346","author":"Jick","year":"1995","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"key":"13_33627504","first-page":"3","volume":"70","year":"2004","ISSN":"https:\/\/id.crossref.org\/issn\/1879-0518","issn-type":"print"},{"issue":"2","key":"14_30248790","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/ajh.21059","volume":"83","author":"Pomp","year":"2008","journal-title":"American journal of hematology","ISSN":"https:\/\/id.crossref.org\/issn\/0361-8609","issn-type":"print"},{"issue":"9","key":"15_28769596","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.2337\/dc07-0642","volume":"30","year":"2007","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"7","key":"17_30718268","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1093\/humrep\/den095","volume":"23","year":"2008","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"key":"18_34082346","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/oby.2008.491","volume":"17","year":"2009","journal-title":"OBESITY"},{"issue":"1","key":"20_17966410","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/humrep\/deh098","volume":"19","author":"The Rotterdam ESHRE\/ASRM-sponsored PCOS consensus","year":"2004","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"11","key":"21_22547385","doi-asserted-by":"publisher","first-page":"4237","DOI":"10.1210\/jc.2006-0178","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"22_29863674","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1210\/jc.2007-2053","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"6","key":"23_27977364","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1210\/jc.2007-0190","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4","key":"24_3376086","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1159\/000205234","volume":"17","author":"Clauss","year":"1957","journal-title":"Acta haematologica","ISSN":"https:\/\/id.crossref.org\/issn\/0001-5792","issn-type":"print"},{"issue":"8828","key":"25_10035880","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/0140-6736(92)93147-F","volume":"340","author":"Celermajer","year":"1992","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"2","key":"26_11474186","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0735-1097(01)01746-6","volume":"39","author":"Corretti","year":"2002","journal-title":"Journal of the American College of Cardiology","ISSN":"https:\/\/id.crossref.org\/issn\/0735-1097","issn-type":"print"},{"issue":"9","key":"27_14434202","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1161\/01.ATV.13.9.1327","volume":"13","author":"Fryer","year":"1993","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology","ISSN":"https:\/\/id.crossref.org\/issn\/0276-5047","issn-type":"print"},{"issue":"10","key":"28_5446673","doi-asserted-by":"crossref","first-page":"783","DOI":"10.7326\/0003-4819-111-10-783","volume":"111","author":"Barrett-Connor","year":"1989","journal-title":"Annals of Internal Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0003-4819","issn-type":"print"},{"issue":"8","key":"29_19405438","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/oby.2005.177","volume":"13","author":"Canoy","year":"2005","journal-title":"Obesity","ISSN":"https:\/\/id.crossref.org\/issn\/1071-7323","issn-type":"print"},{"issue":"2","key":"30_18619504","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/sj.ijo.0802827","volume":"29","author":"Akbartabartoori","year":"2005","journal-title":"International journal of obesity","ISSN":"https:\/\/id.crossref.org\/issn\/0307-0565","issn-type":"print"},{"key":"31_34082347","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/sj.ijo.0800435","volume":"21","year":"1997","journal-title":"INTERNATIONAL JOURNAL OF OBESITY AND RELATED METABOLIC DISORDERS"},{"key":"32_34082348","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1046\/j.1467-789X.2002.00056.x","volume":"3","year":"2002","journal-title":"OBESITY REVIEWS"},{"key":"33_34082349","first-page":"813","volume":"4","year":"2006","journal-title":"CLINICAL ADVANCES IN HEMATOLOGY AND ONCOLOGY"},{"issue":"2","key":"34_30071370","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/humrep\/dem379","volume":"23","year":"2008","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"3","key":"35_17522416","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1093\/humrep\/deg120","volume":"18","author":"Seaman","year":"2003","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"5","key":"36_17611013","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1210\/jc.2002-021528","volume":"88","author":"Diamanti-Kandarakis","year":"2003","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1","key":"37_17466191","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1210\/jc.2002-020997","volume":"88","author":"Morin-Papunen","year":"2003","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"38_22962604","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/humrep\/del407","volume":"22","year":"2007","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"5","key":"39_17851825","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1046\/j.1365-2796.2003.01213.x","volume":"254","author":"Wulffel\u00a0\u00a0","year":"2003","journal-title":"Journal of internal medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0954-6820","issn-type":"print"},{"key":"40_34082350","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1055\/s-2002-23489","volume":"110","year":"2002","journal-title":"EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY AND DIABETES"},{"issue":"4","key":"41_18756228","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1093\/humrep\/deh700","volume":"20","year":"2005","journal-title":"Human Reproduction","ISSN":"https:\/\/id.crossref.org\/issn\/0268-1161","issn-type":"print"},{"issue":"2","key":"42_27941920","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1080\/00016340600855946","volume":"86","author":"Carlsen","year":"2007","journal-title":"Acta obstetricia et gynecologica Scandinavica","ISSN":"https:\/\/id.crossref.org\/issn\/0001-6349","issn-type":"print"},{"issue":"9","key":"43_22527132","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1001\/archpedi.160.9.933","volume":"160","author":"Pinhas-Hamiel","year":"2006","journal-title":"Archives of Pediatrics and Adolescent Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0096-8994","issn-type":"print"},{"issue":"9","key":"44_10463074","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.2337\/diacare.23.9.1227","volume":"23","author":"Bauman","year":"2000","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"3","key":"45_30604258","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.amjmed.2007.10.025","volume":"121","author":"Zakai","year":"2008","journal-title":"The American journal of medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9343","issn-type":"print"},{"issue":"5","key":"46_23576400","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.2337\/dc06-2142","volume":"30","year":"2007","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"key":"47_34082351","doi-asserted-by":"crossref","first-page":"392E","DOI":"10.1152\/ajpendo.2001.281.2.E392","volume":"281","year":"2001","journal-title":"AMERICAN JOURNAL OF PHYSIOLOGYENDOCRINOLOGY AND METABOLISM"},{"issue":"3","key":"48_18902746","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.thromres.2004.11.026","volume":"116","author":"Carmassi","year":"2005","journal-title":"Thrombosis research","ISSN":"https:\/\/id.crossref.org\/issn\/0049-3848","issn-type":"print"},{"issue":"4","key":"49_30953131","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1210\/er.2007-0041","volume":"29","year":"2008","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"5","key":"50_18836704","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1016\/j.fertnstert.2004.11.070","volume":"83","author":"DeUgarte","year":"2005","journal-title":"Fertility and sterility","ISSN":"https:\/\/id.crossref.org\/issn\/0015-0282","issn-type":"print"},{"issue":"1","key":"51_21074748","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1210\/jc.2005-1804","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"52_34082352","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.metabol.2006.12.021","volume":"56","year":"2007","journal-title":"METABOLISM CLINICAL AND EXPERIMENTAL"},{"issue":"9","key":"53_31400915","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1210\/jc.2008-0626","volume":"93","year":"2008","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"54_17588729","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1210\/er.2001-0025","volume":"24","author":"Wu","year":"2003","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"4","key":"55_18134495","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1177\/1099800403262927","volume":"5","author":"Littleton-Kearney","year":"2004","journal-title":"Biological Research For Nursing","ISSN":"https:\/\/id.crossref.org\/issn\/1099-8004","issn-type":"print"},{"key":"56_28377958","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1042\/CS19980148","volume":"95","year":"1998","journal-title":"Clinical science","ISSN":"https:\/\/id.crossref.org\/issn\/0009-9287","issn-type":"print"},{"issue":"11","key":"57_19578261","doi-asserted-by":"publisher","first-page":"6072","DOI":"10.1210\/jc.2005-0965","volume":"90","year":"2005","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4","key":"58_31579240","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1530\/EJE-08-0507","volume":"159","year":"2008","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/160\/3\/469.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/160\/3\/469.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:22:44Z","timestamp":1676391764000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/160\/3\/469\/6676277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":56,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-08-0725","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}