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      Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment

       
      Nature Reviews Endocrinology
      Springer Nature

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          Abstract

          Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. The aetiology of this syndrome remains largely unknown, but mounting evidence suggests that PCOS might be a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. The diagnosis and treatment of PCOS are not complicated, requiring only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches addressing hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders. This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS.

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          Most cited references135

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          The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

          Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.
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            Diagnosis and classification of diabetes mellitus.

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              Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement.

              The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.
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                Author and article information

                Journal
                Nature Reviews Endocrinology
                Nat Rev Endocrinol
                Springer Nature
                1759-5029
                1759-5037
                March 23 2018
                March 23 2018
                :
                :
                Article
                10.1038/nrendo.2018.24
                29569621
                eefe48b1-9ef0-4f18-aba3-8aff23f6ded3
                © 2018
                History

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