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This is largely dependent on the influence of obesity and metabolic alterations, including an insulin\u2010resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity <jats:italic>per se<\/jats:italic> represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long\u2010term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.<\/jats:p>","DOI":"10.1111\/j.1471-0528.2006.00990.x","type":"journal-article","created":{"date-parts":[[2006,7,7]],"date-time":"2006-07-07T23:19:52Z","timestamp":1152314392000},"page":"1148-1159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":285,"title":["Review article: The impact of obesity on reproduction in women with polycystic ovary syndrome"],"prefix":"10.1111","volume":"113","author":[{"given":"R","family":"Pasquali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Gambineri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Pagotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,10]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041536"},{"key":"e_1_2_8_3_2","first-page":"377","volume-title":"Polycystic Ovary Syndrome","author":"Zawadski JK","year":"1992"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh098"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1365.014"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801994"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67483-1"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2004.03.004"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2004.00147.x"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmg024"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031122"},{"key":"e_1_2_8_12_2","unstructured":"World Health Organization.Obesity. 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