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      UPLC/Q-TOF-MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome

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          Abstract

          The present study aimed to develop novel diagnostic methods for polycystic ovarian syndrome (PCOS) by screening and identifying specific PCOS-associated metabolic markers using plasma metabolomics. Ultra-performance liquid chromatography/quadrapole-time of flight-mass spectrometry was adopted to establish the plasma metabolic fingerprint of 49 patients and 50 normal controls, in order to screen the potential metabolic markers. In addition, these markers were integrated with the clinical indexes, followed by focused analysis to obtain diagnostic markers. The present results demonstrated that not only was the concentration of palmitoyl sphingomyelin in plasma of patients with PCOS significantly increased; however, a statistically significant difference between the two PCOS subgroups was additionally demonstrated. At the same time, the concentrations of cyclic guanosine monophosphate (cGMP) and dehydroepiandrosterone sulphate in the plasma of patients of the subgroup 1 were significantly elevated. These markers were additionally integrated with the clinical index number of follicles in the left ovary and high-density lipoprotein (HDL-C), followed by receiver operating characteristic curve analysis, which demonstrated a diagnostic accuracy of ~90% in the control and the two subgroups. The integrated marker system consisting of palmitoyl sphingomyelin, cGMP and androsterone sulfate, as well as the number of left follicles and HDL-C may be used for the accurate diagnosis and classification of PCOS. These results confirmed that the abnormalities in hormone metabolism and lipid metabolism disorder were primarily involved in the onset of PCOS.

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          Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients.

          Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous endocrine disorder affecting women of reproductive age, associated with endocrinopathy and metabolic abnormalities. Although some metabolic parameters have been investigated, very little information has been reported on the changes of small metabolites in biofluids. The aim of this study was to establish the metabolic profile of PCOS and compare it with that of controls. In this cross-sectional study of 34 women with PCOS and 36 controls, contents of small metabolites and lipids in plasma samples were measured using nuclear magnetic resonance (NMR)-based techniques and analyzed using multivariate statistical methods. Significant decrease (P < 0.05) in the levels of amino acids (leucine, isoleucine, methionine, glutamine, and arginine), citrate, choline, and glycerophosphocholine/phosphocholine (GPC/PC), and increase (P < 0.05) in the levels of lactate, dimethylamine (DMA), creatine, and N-acetyl glycoproteins were observed in PCOS patients compared with the controls. Subgroups of patients with obesity, metabolic syndrome, or hyperandrogenism exhibited greater metabolic deviations than their corresponding subgroups without these factors. PCOS patients have perturbations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and gut microflora, as well as mild disturbances in glucose and lipid metabolism. The elevated level of N-acetyl glycoproteins demonstrates the existence of low-grade chronic inflammation in PCOS patients.
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            Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria.

            To determine the prevalence of elevated total and free T, and DHEAS, alone and in combination, in patients with polycystic ovary syndrome (PCOS). Cross-sectional analysis. Tertiary care academic medical center. Seven hundred twenty patients diagnosed with PCOS according to the National Institutes of Health 1990 criteria. History, physical examination, and blood sampling. Hyperandrogenemia, defined as at least one androgen value above the 95th percentile of 98 healthy control women (i.e., total T >88 ng/dL, free T >0.75 ng/dL, and DHEAS >2,750 ng/mL). A total of 716 subjects with PCOS were included. The overall prevalence of hyperandrogenemia in PCOS was 75.3%. Supranormal levels of free T were present in 57.6%, of total T in 33.0%, and of DHEAS in 32.7% of patients with PCOS. When assessing the prevalence of two abnormal values, the prevalence of simultaneously elevated androgens was lowest with total T and DHEAS (1.7%) and highest with total T and free T (20.4%). Altogether, simultaneous elevations in all three markers were found in 8.7% of subjects with PCOS. Approximately three-fourths of patients with PCOS diagnosed by the National Institutes of Health 1990 criteria have evidence of hyperandrogenemia; the single most predictive assay was the measurement of free T with approximately 60% of patients demonstrating supranormal levels. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome.

              Hirsutism is a common endocrine disorder, defined as increased growth of terminal hairs in a male pattern. Hirsutism is most often caused by polycystic ovary syndrome (PCOS), whereas only 5% patients are diagnosed with rare endocrine diseases. PCOS may be considered a multiorgan disease causing not only increased adrenal and ovarian sex hormone secretion but also changed secretion of gonadotrophins, growth hormone, and adrenocorticotrophic hormone (ACTH) from the pituitary. The majority of patients with PCOS are insulin resistant and PCOS is characterized by an increased inflammatory state with abdominal obesity and increased secretion of interleukins, chemokines, and adipokines. PCOS is therefore associated with an increased risk of the metabolic syndrome and type 2 diabetes (T2D). Patients with hirsutism present with increased bone mineral density despite decreased D-vitamin levels. The etiology to hirsutism and PCOS is most likely multifactorial including both genetic and environmental factors such as increased fetal stress and intrauterine growth retardation. In the present review, we give a comprehensive overview of the pathophysiology and multiple endocrine disturbances of hirsutism and PCOS.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                January 2019
                12 November 2018
                12 November 2018
                : 19
                : 1
                : 280-292
                Affiliations
                [1 ]Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China
                [2 ]Department of Obstetrics and Gynecology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
                [3 ]Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
                Author notes
                Correspondence to: Professor Yiming Wang, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, 1 Qinghuayuan, Beijing 100084, P.R. China, E-mail: wangyim@ 123456tsinghua.edu.cn
                Professor Aijun Sun, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Beijing 100730, P.R. China, E-mail: 2249256116@ 123456qq.com
                [*]

                Contributed equally

                Article
                mmr-19-01-0280
                10.3892/mmr.2018.9643
                6297741
                30431132
                724f8e1b-0291-4e26-8929-8b76d57c727b
                Copyright: © Fan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 05 July 2017
                : 18 September 2018
                Categories
                Articles

                polycystic ovarian syndrome,metabolomics,potential metabolic marker,integrated marker system,accurate diagnosis

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