{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:49:11Z","timestamp":1788468551820,"version":"build-2803163510"},"reference-count":45,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,10,1]]},"DOI":"10.1210\/jc.2005-2250","type":"journal-article","created":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T22:09:15Z","timestamp":1153865355000},"page":"3970-3980","source":"Crossref","is-referenced-by-count":189,"title":["Treatment with Flutamide, Metformin, and Their Combination Added to a Hypocaloric Diet in Overweight-Obese Women with Polycystic Ovary Syndrome: A Randomized, 12-Month, Placebo-Controlled Study"],"prefix":"10.1210","volume":"91","author":[{"given":"Alessandra","family":"Gambineri","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Patton","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Vaccina","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Cacciari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Maria","family":"Morselli-Labate","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cavazza","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"key\n\t\t\t\t2019041114124360100_R1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199509283331307","article-title":"Polycystic ovary syndrome","volume":"333","author":"Franks","year":"1995","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t2019041114124360100_R2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1210\/jcem-68-1-173","article-title":"Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss","volume":"68","author":"Pasquali","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R3","first-page":"556","article-title":"17\u03b1-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss","volume":"82","author":"Jakubowicz","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R4","first-page":"4075","article-title":"Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17\u03b1 activity and serum androgens","volume":"82","author":"Nestler","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R5","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1056\/NEJM199806253382603","article-title":"Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome","volume":"338","author":"Nestler","year":"1998","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t2019041114124360100_R6","first-page":"139","article-title":"Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation","volume":"85","author":"Moghetti","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R7","first-page":"1626","article-title":"Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial","volume":"86","author":"Azziz","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1210\/jcem.83.1.4500","article-title":"Hormonal effects of flutamide in young women with polycystic ovary syndrome","volume":"83","author":"De Leo","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R9","first-page":"4047","article-title":"Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone","volume":"85","author":"Eagleson","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R10","first-page":"3251","article-title":"Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide","volume":"85","author":"Iba\u0301nez","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/00060793-200212000-00004","article-title":"Treatment of the polycystic ovary syndrome with lifestyle intervention","volume":"9","author":"Pasquali","year":"2002","journal-title":"Curr Opin Endocrinol Diab"},{"key":"key\n\t\t\t\t2019041114124360100_R12","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1210\/jc.2002-020815","article-title":"Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome","volume":"88","author":"Moran","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R13","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.fertnstert.2003.08.023","article-title":"A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome","volume":"81","author":"Stamets","year":"2004","journal-title":"Fertil Steril"},{"key":"key\n\t\t\t\t2019041114124360100_R14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1365-2265.1992.tb02909.x","article-title":"Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome","volume":"36","author":"Kiddy","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"key":"key\n\t\t\t\t2019041114124360100_R15","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1210\/jcem.85.8.6738","article-title":"Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome","volume":"85","author":"Pasquali","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2265.2004.01973.x","article-title":"Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome","volume":"60","author":"Gambineri","year":"2004","journal-title":"Clin Endocrinol (Oxf)"},{"key":"key\n\t\t\t\t2019041114124360100_R17","author":"WHO","year":"1997"},{"key":"key\n\t\t\t\t2019041114124360100_R18","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","volume":"19","author":"The Rotterdam ESHRE\/ASMR-sponsored PCOS consensus workshop group","year":"2004","journal-title":"Hum Reprod"},{"key":"key\n\t\t\t\t2019041114124360100_R19","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/jcem-21-11-1440","article-title":"Clinical assessment of body hair growth in women","volume":"21","author":"Ferriman","year":"1961","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R20","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1210\/jc.2004-2490","article-title":"Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome","volume":"90","author":"Gambineri","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R21","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1093\/ajcn\/36.5.936","article-title":"A short questionnaire for the measurement of habitual physical activity in epidemiological studies","volume":"36","author":"Baecke","year":"1982","journal-title":"Am J Clin Nutr"},{"key":"key\n\t\t\t\t2019041114124360100_R22","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1046\/j.1365-2265.1999.00701.x","article-title":"The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment","volume":"50","author":"Pasquali","year":"1999","journal-title":"Clin Endocrinol (Oxf)"},{"key":"key\n\t\t\t\t2019041114124360100_R23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"key\n\t\t\t\t2019041114124360100_R24","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"},{"key":"key\n\t\t\t\t2019041114124360100_R25","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"key\n\t\t\t\t2019041114124360100_R26","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"key\n\t\t\t\t2019041114124360100_R27","first-page":"SPSS","article-title":"Inc","volume":"Chicago","author":"Norusis","year":"1990","journal-title":"SPSS\/PC + 4.0 base and advanced statistics manuals."},{"key":"key\n\t\t\t\t2019041114124360100_R28","author":"Dixon","year":"1990"},{"key":"key\n\t\t\t\t2019041114124360100_R29","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.fertnstert.2004.02.104","article-title":"A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and\/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study","volume":"82","author":"Hoeger","year":"2004","journal-title":"Fertil Steril"},{"key":"key\n\t\t\t\t2019041114124360100_R30","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1016\/S0140-6736(00)03491-7","article-title":"Effect of sibutramine on weight maintenance after weight loss: a randomized trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance","volume":"356","author":"James","year":"2000","journal-title":"Lancet"},{"key":"key\n\t\t\t\t2019041114124360100_R31","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/sj.ijo.0801687","article-title":"The Swedish Obese Subjects (SOS) study: rationale and results","volume":"1","author":"Torgerson","year":"2001","journal-title":"Int J Obes Relat Metab Disord"},{"key":"key\n\t\t\t\t2019041114124360100_R32","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1136\/bmj.327.7421.951","article-title":"Metformin in polycystic ovary syndrome: systematic review and meta-analysis","volume":"327","author":"Lord","year":"2003","journal-title":"BMJ"},{"key":"key\n\t\t\t\t2019041114124360100_R33","first-page":"CD003053","article-title":"Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome","volume":"3","author":"Lord","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"key\n\t\t\t\t2019041114124360100_R34","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/S1472-6483(10)60928-5","article-title":"Should insulin-sensitizing drugs be used in the treatment of polycystic ovary syndrome?","volume":"8","author":"Cheang","year":"2004","journal-title":"Reprod Biomed Online"},{"key":"key\n\t\t\t\t2019041114124360100_R35","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1210\/edrv.20.4.0374","article-title":"The insulin-related ovarian regulatory system in health and disease","volume":"20","author":"Poretsky","year":"1999","journal-title":"Endocr Rev"},{"key":"key\n\t\t\t\t2019041114124360100_R36","first-page":"2057","article-title":"Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women","volume":"80","author":"Crave","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R37","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/humupd\/dmi013","article-title":"Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome?","volume":"11","author":"Abbott","year":"2005","journal-title":"Hum Reprod Update"},{"key":"key\n\t\t\t\t2019041114124360100_R38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/j.1550-8528.1993.tb00614.x","article-title":"Visceral obesity: a \u201ccivilization syndrome.\u201d","volume":"1","author":"Bjo\u0308rntorp","year":"1993","journal-title":"Obes Res"},{"key":"key\n\t\t\t\t2019041114124360100_R39","first-page":"2198","article-title":"Exogenous androgens influence body composition and regional body fat distribution in obese post-menopausal women: a clinical research center study","volume":"81","author":"Lovejoy","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R40","first-page":"291","article-title":"The regulation of adipose tissue distribution in humans","volume":"20","author":"Bjo\u0308rntorp","year":"1996","journal-title":"Int J Obes Relat Metab Dis"},{"key":"key\n\t\t\t\t2019041114124360100_R41","first-page":"E851","article-title":"Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats","volume":"262","author":"Holmang","year":"1992","journal-title":"Am J Physiol"},{"key":"key\n\t\t\t\t2019041114124360100_R42","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2337\/diab.45.5.615","article-title":"Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment","volume":"45","author":"Rincon","year":"1996","journal-title":"Diabetes"},{"key":"key\n\t\t\t\t2019041114124360100_R43","first-page":"265","article-title":"Induction of insulin resistance by androgens and estrogens","volume":"79","author":"Polderman","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R44","first-page":"952","article-title":"The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women","volume":"81","author":"Moghetti","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041114124360100_R45","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0026-0495(95)90062-4","article-title":"Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome","volume":"44","author":"Diamanti-Kandarakis","year":"1995","journal-title":"Metabolism"}],"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/91\/10\/3970\/9063211\/jcem3970.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T09:08:17Z","timestamp":1587114497000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/91\/10\/3970\/2656548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,1]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2006,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2005-2250","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,1]]}}}