{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:41:44Z","timestamp":1790242904516,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T00:00:00Z","timestamp":1225843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Context and aim\u2002<\/jats:bold> Metformin plus oestro\u2010progestagen is a combination treatment for non\u2010obese women with hyperinsulinaemic androgen excess. We explored whether low\u2010dose pioglitazone (Pio) and flutamide (Flu) has readily detectable add\u2010on effects.<\/jats:p><jats:p><jats:bold>Design patients, intervention\u2002<\/jats:bold> Randomized, double\u2010placebo pilot study over 24\u00a0months; 38 women with hyperinsulinaemic androgen excess (mean age 20\u00a0years; BMI 23\u00b77\u00a0kg\/m<jats:sup>2<\/jats:sup>); all women received metformin and an oestro\u2010progestagen for 24\u00a0months, and add\u2010on Flu (62\u00b75\u00a0mg\/day; 21\/28 days) for 18\u00a0months. A first randomization was performed at start of the study, for Pio (7\u00b75\u00a0mg\/day; 21\/28 days) <jats:italic>vs.<\/jats:italic> Pio\u2010placebo, with a cross\u2010over of Pio subgroups at 18\u00a0month. A second randomization was performed at 18\u00a0months, for Flu <jats:italic>vs.<\/jats:italic> Flu\u2010placebo until 24\u00a0months.<\/jats:p><jats:p><jats:bold>Main outcomes\u2002<\/jats:bold> Intima media thickness (IMT); body composition by absorptiometry; abdominal fat partitioning by magnetic resonance; circulating glucose, insulin, IGF\u2010I, androgens, LDL : HDL ratio, RBP4, vaspin.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Add\u2010on effects of Pio included a gain of lean mass (mirrored by a loss of fat) and an accelerated lowering of IMT (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00\u00b7001). Add\u2010on effects of flutamide included a further reduction of androgen excess. Between 0 and 18\u00a0months, women lost a quarter of their visceral fat (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b7001; independently of Pio); beyond 18\u00a0months, a rebound of visceral fat occurred in women who had stopped Pio and Flu. Between 0 and 24\u00a0months, insulin sensitivity increased, as did circulating RBP\u20104 and vaspin (all <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7001).<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> Low\u2010dose Pio and Flu further improve long\u2010term markers \u2013 such as IMT, lean mass and visceral fat \u2013 when jointly added to a treatment of metformin plus an oestro\u2010progestagen in non\u2010obese women with hyperinsulinaemic androgen excess.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03472.x","type":"journal-article","created":{"date-parts":[[2008,11,5]],"date-time":"2008-11-05T08:21:20Z","timestamp":1225873280000},"page":"351-357","source":"Crossref","is-referenced-by-count":24,"title":["Low\u2010dose pioglitazone and low\u2010dose flutamide added to metformin and oestro\u2010progestagens for hyperinsulinaemic women with androgen excess: add\u2010on benefits disclosed by a randomized double\u2010placebo study over 24\u00a0months"],"prefix":"10.1111","volume":"71","author":[{"given":"Lourdes","family":"Ib\u00e1\u00f1ez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"L\u00f3pez\u2010Bermejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goya","family":"Enr\u00edquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Del R\u00edo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"De Zegher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,8,14]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.9.1165"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(94)90209-7"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.12.4075"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806253382603"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3526"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.8.7756"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei072"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041536"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2012"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0047"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmi054"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2684"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.03137.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054862"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.264"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.10.011"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2759"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0102"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","unstructured":"Hutchison S.K. 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