title: Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause.
abstract: Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intra-uterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil doctor_asmelo@yahoo.com.br.
authors.forename: Anderson Sanches
authors.initials: AS
authors.lastname: de Melo
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sabrine Vilan
authors.initials: SV
authors.lastname: Dias
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ricardo de Carvalho
authors.initials: Rde C
authors.lastname: Cavalli
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Viviane Cunha
authors.initials: VC
authors.lastname: Cardoso
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Bettiol
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Barbieri
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rui Alberto
authors.initials: RA
authors.lastname: Ferriani
authors.affiliation: Unit of Human Reproduction and Gynecological EndocrinologyDepartment of Gynecology and ObstetricsDepartment of PaediatricsMedical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Campus Universitário - Monte Alegre, CEP: 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Carolina Sales
authors.initials: CS
authors.lastname: Vieira
mesh_terms: D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007236:Infant, Small for Gestational Age; D008593:Menopause; D011085:Polycystic Ovary Syndrome / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide