title: Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth.
abstract: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela ; Institute of Clinical Immunology, The University of Los Andes, Mérida 5101, Venezuela.
authors.forename: Joselyn
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: Mervin
authors.initials: M
authors.lastname: Chávez
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: Luis
authors.initials: L
authors.lastname: Olivar
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: Milagros
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: Jessenia
authors.initials: J
authors.lastname: Morillo
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: José
authors.initials: J
authors.lastname: Mejías
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: María
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
authors.forename: Valmore
authors.initials: V
authors.lastname: Bermúdez