Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy
Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose...
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| Veröffentlicht in: | PloS one 2011-12, Vol.6 (12), p.e29052 |
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| description | Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients. |
| doi_str_mv | 10.1371/journal.pone.0029052 |
| format | Article |
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Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0029052</identifier><identifier>PMID: 22194988</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abdominal Fat - drug effects ; Abdominal Fat - metabolism ; Acids ; Adipose tissue ; Androgens ; Antidiabetics ; Arteriosclerosis ; Atherosclerosis ; Biology ; Biomarkers - metabolism ; Biomedical research ; Blood cholesterol ; Cardiovascular diseases ; Carotid Intima-Media Thickness ; Chemistry ; Cholesterol ; Chromatography, Gas ; Chromatography, Liquid ; Diabetes ; Dicarboxylic Acids - blood ; Dose-Response Relationship, Drug ; Drug dosages ; Drug Therapy, Combination ; Dyslipidemia ; Endocrinology ; Endothelium ; Female ; Flutamide ; Flutamide - administration & dosage ; Flutamide - pharmacology ; Flutamide - therapeutic use ; Health ; Health risks ; High density lipoprotein ; Humans ; Hypertension ; Hypoglycemic agents ; Insulin ; Insulin resistance ; Internal medicine ; Linoleic Acid - chemistry ; Linoleic Acid - metabolism ; Lipoproteins (high density) ; Lipoproteins (low density) ; Lipoproteins - metabolism ; Low density lipoprotein ; Low density lipoproteins ; Magnetic Resonance Spectroscopy ; Malalties de l'ovari ; Markers ; Medicine ; Metabolic disorders ; Metabolic syndrome ; Metabolites ; Metabolomics ; Metabolomics - methods ; Metabòlits ; Metformin ; Metformin - administration & dosage ; Metformin - pharmacology ; Metformin - therapeutic use ; Multivariate Analysis ; NMR ; Nuclear magnetic resonance ; Obesity ; Ovary diseases ; Oxidation ; Oxidation-Reduction - drug effects ; Oxidation-reduction reactions ; Particulates ; Pharmacy ; Physiology ; Pioglitazone ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - blood ; Polycystic Ovary Syndrome - drug therapy ; Polycystic Ovary Syndrome - metabolism ; Spectrometry, Mass, Electrospray Ionization ; Thiazolidinediones - administration & dosage ; Thiazolidinediones - pharmacology ; Thiazolidinediones - therapeutic use ; Young Adult</subject><ispartof>PloS one, 2011-12, Vol.6 (12), p.e29052</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Vinaixa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>cc-by (c) Vinaixa, Maria et al., 2011 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a></rights><rights>Vinaixa et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c733t-b2c854ae945e1ff74815315f22e058c578d373f2ac389e6cdbe241d38f022ef03</citedby><cites>FETCH-LOGICAL-c733t-b2c854ae945e1ff74815315f22e058c578d373f2ac389e6cdbe241d38f022ef03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241700/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241700/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,26974,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22194988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wold, Loren E.</contributor><creatorcontrib>Vinaixa, Maria</creatorcontrib><creatorcontrib>Rodriguez, Miguel Angel</creatorcontrib><creatorcontrib>Samino, Sara</creatorcontrib><creatorcontrib>Díaz, Marta</creatorcontrib><creatorcontrib>Beltran, Antoni</creatorcontrib><creatorcontrib>Mallol, Roger</creatorcontrib><creatorcontrib>Bladé, Cinta</creatorcontrib><creatorcontrib>Ibañez, Lourdes</creatorcontrib><creatorcontrib>Correig, Xavier</creatorcontrib><creatorcontrib>Yanes, Oscar</creatorcontrib><title>Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.</description><subject>Abdominal Fat - drug effects</subject><subject>Abdominal Fat - metabolism</subject><subject>Acids</subject><subject>Adipose tissue</subject><subject>Androgens</subject><subject>Antidiabetics</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Biomedical research</subject><subject>Blood cholesterol</subject><subject>Cardiovascular diseases</subject><subject>Carotid Intima-Media Thickness</subject><subject>Chemistry</subject><subject>Cholesterol</subject><subject>Chromatography, Gas</subject><subject>Chromatography, Liquid</subject><subject>Diabetes</subject><subject>Dicarboxylic Acids - blood</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>Drug Therapy, Combination</subject><subject>Dyslipidemia</subject><subject>Endocrinology</subject><subject>Endothelium</subject><subject>Female</subject><subject>Flutamide</subject><subject>Flutamide - 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methods</subject><subject>Metabòlits</subject><subject>Metformin</subject><subject>Metformin - administration & dosage</subject><subject>Metformin - pharmacology</subject><subject>Metformin - therapeutic use</subject><subject>Multivariate Analysis</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Obesity</subject><subject>Ovary diseases</subject><subject>Oxidation</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Oxidation-reduction reactions</subject><subject>Particulates</subject><subject>Pharmacy</subject><subject>Physiology</subject><subject>Pioglitazone</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - blood</subject><subject>Polycystic Ovary Syndrome - drug therapy</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Thiazolidinediones - administration & dosage</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Thiazolidinediones - 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chemistry</topic><topic>Linoleic Acid - metabolism</topic><topic>Lipoproteins (high density)</topic><topic>Lipoproteins (low density)</topic><topic>Lipoproteins - metabolism</topic><topic>Low density lipoprotein</topic><topic>Low density lipoproteins</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Malalties de l'ovari</topic><topic>Markers</topic><topic>Medicine</topic><topic>Metabolic disorders</topic><topic>Metabolic syndrome</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Metabolomics - methods</topic><topic>Metabòlits</topic><topic>Metformin</topic><topic>Metformin - administration & dosage</topic><topic>Metformin - pharmacology</topic><topic>Metformin - therapeutic use</topic><topic>Multivariate Analysis</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Obesity</topic><topic>Ovary diseases</topic><topic>Oxidation</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Oxidation-reduction reactions</topic><topic>Particulates</topic><topic>Pharmacy</topic><topic>Physiology</topic><topic>Pioglitazone</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - blood</topic><topic>Polycystic Ovary Syndrome - drug therapy</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Thiazolidinediones - administration & dosage</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Thiazolidinediones - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vinaixa, Maria</creatorcontrib><creatorcontrib>Rodriguez, Miguel Angel</creatorcontrib><creatorcontrib>Samino, Sara</creatorcontrib><creatorcontrib>Díaz, Marta</creatorcontrib><creatorcontrib>Beltran, Antoni</creatorcontrib><creatorcontrib>Mallol, Roger</creatorcontrib><creatorcontrib>Bladé, Cinta</creatorcontrib><creatorcontrib>Ibañez, Lourdes</creatorcontrib><creatorcontrib>Correig, Xavier</creatorcontrib><creatorcontrib>Yanes, Oscar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vinaixa, Maria</au><au>Rodriguez, Miguel Angel</au><au>Samino, Sara</au><au>Díaz, Marta</au><au>Beltran, Antoni</au><au>Mallol, Roger</au><au>Bladé, Cinta</au><au>Ibañez, Lourdes</au><au>Correig, Xavier</au><au>Yanes, Oscar</au><au>Wold, Loren E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-12-16</date><risdate>2011</risdate><volume>6</volume><issue>12</issue><spage>e29052</spage><pages>e29052-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22194988</pmid><doi>10.1371/journal.pone.0029052</doi><tpages>e29052</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-12, Vol.6 (12), p.e29052 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312178452 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); Recercat; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abdominal Fat - drug effects Abdominal Fat - metabolism Acids Adipose tissue Androgens Antidiabetics Arteriosclerosis Atherosclerosis Biology Biomarkers - metabolism Biomedical research Blood cholesterol Cardiovascular diseases Carotid Intima-Media Thickness Chemistry Cholesterol Chromatography, Gas Chromatography, Liquid Diabetes Dicarboxylic Acids - blood Dose-Response Relationship, Drug Drug dosages Drug Therapy, Combination Dyslipidemia Endocrinology Endothelium Female Flutamide Flutamide - administration & dosage Flutamide - pharmacology Flutamide - therapeutic use Health Health risks High density lipoprotein Humans Hypertension Hypoglycemic agents Insulin Insulin resistance Internal medicine Linoleic Acid - chemistry Linoleic Acid - metabolism Lipoproteins (high density) Lipoproteins (low density) Lipoproteins - metabolism Low density lipoprotein Low density lipoproteins Magnetic Resonance Spectroscopy Malalties de l'ovari Markers Medicine Metabolic disorders Metabolic syndrome Metabolites Metabolomics Metabolomics - methods Metabòlits Metformin Metformin - administration & dosage Metformin - pharmacology Metformin - therapeutic use Multivariate Analysis NMR Nuclear magnetic resonance Obesity Ovary diseases Oxidation Oxidation-Reduction - drug effects Oxidation-reduction reactions Particulates Pharmacy Physiology Pioglitazone Polycystic ovary syndrome Polycystic Ovary Syndrome - blood Polycystic Ovary Syndrome - drug therapy Polycystic Ovary Syndrome - metabolism Spectrometry, Mass, Electrospray Ionization Thiazolidinediones - administration & dosage Thiazolidinediones - pharmacology Thiazolidinediones - therapeutic use Young Adult |
| title | Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy |
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