{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:45:57Z","timestamp":1758123957846},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Addition of androgen receptor (AR) blockade (flutamide) to insulin-sensitising therapy (metformin) may confer synergistic benefits in girls with hyperinsulinaemic androgen excess. We hypothesised that girls with shorter AR gene CAG repeat alleles, and thus greater receptor sensitivity, might benefit more from the addition of low-dose flutamide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Open randomised crossover study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, 32 post-menarcheal girls (mean age 12.1 years) with a history of low birth weight and precocious pubarche were subgrouped by CAG genotype (\u2018short\u2019: CAG mean length \u226420, <jats:italic>n<\/jats:italic>=14; \u2018long\u2019: CAG &gt;20, <jats:italic>n<\/jats:italic>=18). Within each subgroup, girls were 1:1 randomised to metformin alone (850\u200amg\/day) or in combination with flutamide (62.5\u200amg\/day) for 12 months. To allow comparisons with no treatment, long-CAG girls randomised to flutamide\u2013metformin, and short-CAG girls randomised to metformin alone were observed for 12 months before treatment. Body composition by absorptiometry, fasting lipid profiles and levels of insulin, glucose and androgens were measured during the first 12 months on each treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all girls, 12 months flutamide\u2013metformin lowered body fat and improved lipid profiles when compared with no treatment. Compared with metformin alone, flutamide\u2013metformin achieved greater reductions in the percentage of body fat and abdominal fat mass in the short-CAG subgroup (<jats:italic>P<\/jats:italic>=0.001 to <jats:italic>P<\/jats:italic>&lt;0.0001). In contrast, in the long-CAG subgroup, flutamide\u2013metformin produced no further improvements when compared with metformin alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In young post-menarcheal girls with preclinical androgen excess, low-dose flutamide\u2013metformin improved body composition and key endocrine\u2013metabolic abnormalities. However, only those girls with genetic markers of greater AR sensitivity may benefit from the addition of flutamide above metformin alone.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-07-0261","type":"journal-article","created":{"date-parts":[[2007,11,5]],"date-time":"2007-11-05T20:49:43Z","timestamp":1194295783000},"page":"661-668","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":11,"title":["Flutamide\u2013metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype"],"prefix":"10.1093","volume":"157","author":[{"given":"Ken K","family":"Ong","sequence":"first","affiliation":[{"name":"1Medical Research Council Epidemiology UnitCambridge CB0 2QQ, UK"},{"name":"2Department of PediatricsUniversity of Cambridge, Cambridge CB0 2QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"de Zegher","sequence":"additional","affiliation":[{"name":"3Department of Woman and ChildUniversity of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"L\u00f3pez-Bermejo","sequence":"additional","affiliation":[{"name":"4DiabetesEndocrinology and Nutrition Unit, Dr Josep Trueta Hospital, 17007 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B","family":"Dunger","sequence":"additional","affiliation":[{"name":"2Department of PediatricsUniversity of Cambridge, Cambridge CB0 2QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"5Endocrinology UnitHospital Sant Joan de D\u00e9u, University of Barcelona, Passeig de Sant Joan de D\u00e9u, 2, 08950 Esplugues, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"9","key":"2_10481308","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1210\/jc.85.9.3484","volume":"85","author":"Mifsud","year":"2000","journal-title":"Journal of Clinical Endocrinology &amp; 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