{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T22:24:07Z","timestamp":1794349447376,"version":"4.9.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eClinicalMedicine"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.eclinm.2025.103594","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T21:59:20Z","timestamp":1761861560000},"page":"103594","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Oral prolonged-release dienogest 2 mg and ethinylestradiol 0.02 mg in a 24\/4-day regimen for polycystic ovary syndrome-associated hirsutism: a double-blind, randomised, placebo-controlled trial"],"prefix":"10.1016","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1472-8313","authenticated-orcid":false,"given":"Roger","family":"Lobo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicyoy","family":"Angulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Colli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-1644","authenticated-orcid":false,"given":"H\u00e9ctor F.","family":"Escobar-Morreale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-4237","authenticated-orcid":false,"given":"Manuel","family":"Luque-Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos","family":"Zatik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-2847","authenticated-orcid":false,"given":"Pedro-Antonio","family":"Regidor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.eclinm.2025.103594_bib1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrendo.2018.24","article-title":"Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment","volume":"14","author":"Escobar-Morreale","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib2","first-page":"106","article-title":"Diagnosis and treatment of polycystic ovary syndrome","volume":"94","author":"Williams","year":"2016","journal-title":"Am Fam Physician"},{"issue":"9","key":"10.1016\/j.eclinm.2025.103594_bib3","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S2213-8587(22)00163-2","article-title":"Polycystic ovary syndrome","volume":"10","author":"Joham","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"8","key":"10.1016\/j.eclinm.2025.103594_bib4","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.3390\/diagnostics12081922","article-title":"Hirsutism, normal androgens and diagnosis of PCOS","volume":"12","author":"Spritzer","year":"2022","journal-title":"Diagnostics"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-024-00511-3","article-title":"Polycystic ovary syndrome","volume":"10","author":"Stener-Victorin","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1741-7015-8-41","article-title":"Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan","volume":"8","author":"Teede","year":"2010","journal-title":"BMC Med"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib7","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1210\/jc.2018-00241","article-title":"Evaluation and treatment of hirsutism in premenopausal women: an endocrine society\u2217 clinical practice guideline","volume":"103","author":"Martin","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/cen.13389","article-title":"Association between biochemical hyperandrogenism parameters and ferriman-gallwey score in patients with polycystic ovary syndrome: a systematic review and meta-regression analysis","volume":"87","author":"Amiri","year":"2017","journal-title":"Clin Endocrinol"},{"issue":"6","key":"10.1016\/j.eclinm.2025.103594_bib9","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.fertnstert.2008.12.138","article-title":"Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the national institutes of health 1990 criteria","volume":"93","author":"Huang","year":"2010","journal-title":"Fertil Steril"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib10","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2008.06.035","article-title":"The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report","volume":"91","author":"Azziz","year":"2009","journal-title":"Fertil Steril"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib11","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/ejendo\/lvaf030","article-title":"The PCOS phenotype in unselected populations study: ethnic variation in population-based normative cut-offs for defining hirsutism","volume":"192","author":"Bizuneh","year":"2025","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.eclinm.2025.103594_bib12","author":"Teede"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib13","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.fertnstert.2023.07.025","article-title":"Recommendations from the 2023 international evidence-Based guideline for the assessment and management of polycystic ovary syndrome","volume":"120","author":"Teede","year":"2023","journal-title":"Fertil Steril"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib14","doi-asserted-by":"crossref","DOI":"10.2196\/resprot.9024","article-title":"Comparing the effects of combined oral contraceptives containing progestins with low androgenic and antiandrogenic activities on the hypothalamic-pituitary-gonadal axis in patients with polycystic ovary syndrome: systematic review and meta-analysis","volume":"7","author":"Amiri","year":"2018","journal-title":"JMIR Res Protoc"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib15","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/humupd\/dmt038","article-title":"The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis","volume":"20","author":"Zimmerman","year":"2014","journal-title":"Hum Reprod Update"},{"issue":"12","key":"10.1016\/j.eclinm.2025.103594_bib16","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3109\/09513590.2013.831834","article-title":"Effects of an oral contraceptive containing estradiol valerate and dienogest on circulating androgen levels and acne in young patients with PCOS: an observational preliminary study","volume":"29","author":"Di Carlo","year":"2013","journal-title":"Gynecol Endocrinol"},{"issue":"10\u201313","key":"10.1016\/j.eclinm.2025.103594_bib17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.steroids.2003.08.008","article-title":"Conception and pharmacodynamic profile of drospirenone","volume":"68","author":"Elger","year":"2003","journal-title":"Steroids"},{"issue":"10","key":"10.1016\/j.eclinm.2025.103594_bib18","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","article-title":"A critical evaluation of simple methods for the estimation of free testosterone in serum","volume":"84","author":"Vermeulen","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"10.1016\/j.eclinm.2025.103594_bib19","first-page":"1976","article-title":"Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS)","volume":"83","author":"Cronin","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.eclinm.2025.103594_bib20","first-page":"1","article-title":"A randomised double-blind trial to determine the bleeding profile of the prolonged-release contraceptive dienogest 2 mg\/ethinylestradiol 0.02 mg versus an immediate-release formulation of drospirenone 3 mg\/ethinylestradiol 0.02 mg","volume":"30","author":"Biskupska-Bodova","year":"2024","journal-title":"Eur J Contracept Reprod Health Care"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/humupd\/dmx039","article-title":"Combined oral contraceptives and\/or antiandrogens versus insulin sensitizers for polycystic ovary syndrome: a systematic review and meta-analysis","volume":"24","author":"Luque-Ram\u00edrez","year":"2017","journal-title":"Hum Reprod Update"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib22","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/humrep\/deg115","article-title":"Ultrasound examination of polycystic ovaries: is it worth counting the follicles?","volume":"18","author":"Jonard","year":"2003","journal-title":"Hum Reprod"},{"issue":"5","key":"10.1016\/j.eclinm.2025.103594_bib23","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1530\/EJE-17-0516","article-title":"Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial","volume":"177","author":"Alpa\u00f1\u00e9s","year":"2017","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib24","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.fertnstert.2012.06.035","article-title":"Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome","volume":"98","author":"Bhattacharya","year":"2012","journal-title":"Fertil Steril"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib25","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1093\/ejendo\/lvad082","article-title":"Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis","volume":"189","author":"Forslund","year":"2023","journal-title":"Eur J Endocrinol"},{"issue":"6","key":"10.1016\/j.eclinm.2025.103594_bib26","doi-asserted-by":"crossref","first-page":"681","DOI":"10.2165\/11536320-000000000-00000","article-title":"Ethinylestradiol\/dienogest in oral contraception","volume":"70","author":"P\u00e9rez-Campos","year":"2010","journal-title":"Drugs"},{"issue":"8","key":"10.1016\/j.eclinm.2025.103594_bib27","article-title":"Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome","volume":"8","author":"Fraison","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"issue":"5","key":"10.1016\/j.eclinm.2025.103594_bib28","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.fertnstert.2011.08.022","article-title":"Reanalyzing the modified Ferriman-Gallwey score: is there a simpler method for assessing the extent of hirsutism?","volume":"96","author":"Cook","year":"2011","journal-title":"Fertil Steril"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib29","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1210\/jc.2010-2279","article-title":"Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome","volume":"96","author":"Manner\u00e5s-Holm","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib30","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/cvr\/cvz180","article-title":"Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring","volume":"116","author":"Manti","year":"2020","journal-title":"Cardiovasc Res"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib31","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/humupd\/dmr042","article-title":"Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society","volume":"18","author":"Escobar-Morreale","year":"2012","journal-title":"Hum Reprod Update"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0010-7824(01)00310-9","article-title":"Effect of dienogest-containing oral contraceptives on lipid metabolism","volume":"65","author":"Wiegratz","year":"2002","journal-title":"Contraception"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1783\/147118910791749416","article-title":"Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: results from a German case-control study","volume":"36","author":"Dinger","year":"2010","journal-title":"J Fam Plann Reprod Health Care"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib34","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1210\/jc.2014-3196","article-title":"Approach to the patient: contraception in women with polycystic ovary syndrome","volume":"100","author":"Yildiz","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.eclinm.2025.103594_bib35","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b2921","article-title":"The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study","volume":"339","author":"van Hylckama Vlieg","year":"2009","journal-title":"BMJ"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib36","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3803\/EnM.2021.958","article-title":"An update on contraception in polycystic ovary syndrome","volume":"36","author":"Oguz","year":"2021","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMcp1514916","article-title":"CLINICAL PRACTICE. Polycystic ovary syndrome","volume":"375","author":"McCartney","year":"2016","journal-title":"N Engl J Med"},{"issue":"7","key":"10.1016\/j.eclinm.2025.103594_bib38","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.3390\/cancers12071766","article-title":"Endocrine risk factors of endometrial cancer: polycystic ovary syndrome, oral contraceptives, infertility, tamoxifen","volume":"12","author":"Ignatov","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/humupd\/dmi046","article-title":"New progestagens for contraceptive use","volume":"12","author":"Sitruk-Ware","year":"2006","journal-title":"Hum Reprod Update"},{"issue":"47","key":"10.1016\/j.eclinm.2025.103594_bib40","doi-asserted-by":"crossref","first-page":"83334","DOI":"10.18632\/oncotarget.19833","article-title":"Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone","volume":"8","author":"Regidor","year":"2017","journal-title":"Oncotarget"},{"issue":"4","key":"10.1016\/j.eclinm.2025.103594_bib41","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.contraception.2008.10.010","article-title":"Efficacy of a combined oral contraceptive containing 0.030 mg ethinylestradiol\/2 mg dienogest for the treatment of papulopustular acne in comparison with placebo and 0.035 mg ethinylestradiol\/2 mg cyproterone acetate","volume":"79","author":"Palombo-Kinne","year":"2009","journal-title":"Contraception"},{"issue":"3","key":"10.1016\/j.eclinm.2025.103594_bib42","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/13625187.2020.1736546","article-title":"Evaluation of different antiandrogenic progestins on clinical and biochemical variables in polycystic ovary syndrome","volume":"25","author":"Morgante","year":"2020","journal-title":"Eur J Contracept Reprod Health Care"},{"issue":"8","key":"10.1016\/j.eclinm.2025.103594_bib43","doi-asserted-by":"crossref","first-page":"883","DOI":"10.4103\/0366-6999.179783","article-title":"Comparison of Drospirenone- with cyproterone acetate-containing oral contraceptives, combined with metformin and lifestyle modifications in women with polycystic ovary syndrome and metabolic disorders: a prospective randomized control trial","volume":"129","author":"Wang","year":"2016","journal-title":"Chin Med J (Engl)"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib44","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humrep\/deh098","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)","volume":"19","author":"Ea-Spcwg","year":"2004","journal-title":"Hum Reprod"},{"issue":"1","key":"10.1016\/j.eclinm.2025.103594_bib45","first-page":"103","article-title":"Effects of sex steroids on skin 5\u03b1 reductase activity in vitro","volume":"78","author":"Cassidenti","year":"1991","journal-title":"Obstet Gynecol"},{"issue":"2","key":"10.1016\/j.eclinm.2025.103594_bib46","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/00016348209156536","article-title":"A comparative longitudinal study on sex hormone binding globulin capacity during estrogen replacement therapy","volume":"61","author":"Helgason","year":"1982","journal-title":"Acta Obstet Gynecol Scand"},{"key":"10.1016\/j.eclinm.2025.103594_bib47","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2020.03.004","article-title":"After another decade: LC\u2013MS\/MS became routine in clinical diagnostics","volume":"82","author":"Seger","year":"2020","journal-title":"Clin Biochem"}],"container-title":["eClinicalMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537025005279?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537025005279?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:34:20Z","timestamp":1794346460000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589537025005279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":47,"alternative-id":["S2589537025005279"],"URL":"https:\/\/doi.org\/10.1016\/j.eclinm.2025.103594","relation":{},"ISSN":["2589-5370"],"issn-type":[{"value":"2589-5370","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Oral prolonged-release dienogest 2 mg and ethinylestradiol 0.02 mg in a 24\/4-day regimen for polycystic ovary syndrome-associated hirsutism: a double-blind, randomised, placebo-controlled trial","name":"articletitle","label":"Article Title"},{"value":"eClinicalMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.eclinm.2025.103594","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"103594"}}