Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review

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Abstract

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

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  • Al-Eisa E Gabr SA Alghadir AH. Effects of supervised aerobic training on the levels of anti-Mullerian hormone and adiposity measures in women with normo-ovulatory and polycystic ovary syndrome. J Pak Med Assoc 67 499-507 2017.

  • Arner P. Human fat cell lipolysis: biochemistry regulation and clinical role. Best Pract Res Clin Endocrinol Metab 19 471-482 2005.

  • Artimani T Karimi J Mehdizadeh M Yavangi M Khanlarzadeh E Ghorbani M Asadi S Kheiripour N. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol 34 148-152 2018.

  • Aytan AN Bastu E Demiral I. Blulut H Dogan M Buyru F. Relationship between hyperandrogenism obesity inflammation and polycystic ovary syndrome. Gynecol Endocrinol 32 709-713 2016.

  • Azziz R Marin C Hoq L Badamgarav E Song P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol 90 4650-4658 2005.

  • Azziz R. Polycystic Ovary Syndrome Is a Family Affair. J Clin Endocrinol Metab 93 1579-1581 2008.

  • Azziz R Carmina E Chen Z Dunaif A Laven JS Legro RS Lizneva D Natterson-Horowtiz B Teede HJ Yildiz BO. Polycystic ovary syndrome. Nat Rev Dis Primers 2 16057 2016.

  • Bachanek M Abdalla N Cendrowski K Sawicki W. Value of ultrasonography in the diagnosis of polycystic ovary syndrome - literature review. J Ultrason 15 410-422 2015.

  • Bachelot A. Polycystic ovarian syndrome: clinical and biological diagnosis. Ann Biol Clin Ann Biol Clin (Paris) 74 661-667 2016.

  • Bagatini SR. Polimorfismos do gene da adiponectina e variaveis clinicas metabolicas e hormonais em mulheres com ousem a sindrome dos ovarios policisticos (PCOS) e a investigacao de um modelo animal para o estudo da PCOS. Doctoral thesis - Physiology Program - Universidade Federal do Rio Grande do Sul. Porto Alegre Rio Grande do Sul 2010.

  • Barbosa-Desongles A Hernandez C Simo R Selva DM. Testosterone induces cell proliferation and cell cycle gene overexpression in human visceral preadipocytes. Am J Physiol Cell Physiol 305 C355-C359 2013.

  • Bartha JL Comino-Delgado R Romero-Carmona R Gomez-Jaen MC. Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scand 79 839-845 2000.

  • Birukov KG. Oxidized lipids: the two faces of vascular inflammation. Curr Atheroscler Rep 8 223-231 2006.

  • Burchall GF Piva TJ Linden MD Gibson-Helm ME Ranasinha S Teede HJ. Comprehensive assessment of the hemostatic system in polycystic ovarian syndrome. Semin Thromb Hemost 42 55-62 2016.

  • Burt Solorzano CM Beller JP Abshire MY Collins JS McCartney CR Marshall JC. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids 77 332-337 2012.

  • Burtis CA Ashwood EA Tietz BD. Fundamentos de Quimica Clinica 6ed. Filadelfia: Saunders pp. 984 2008.

  • Carvalho LML Ferreira CN Soter MO Sales MF Rodrigues KF Martins SR Candido AL Reis FM Silva IFO Campos FMF Gomes KB. Microparticles: Inflammatory and haemostatic biomarkers in Polycystic Ovary Syndrome. Mol Cell Endocrinol 443 155-162 2017a.

  • Carvalho LML Ferreira CN De Oliveira DKD Rodrigues KD Duarte RCF Teixeira MFA Xavier LB Candido AL Reis FM Silva IFO Campos FMF Gomes KB. Haptoglobin levels but not Hp1-Hp2 polymorphism are associated with polycystic ovary syndrome. J Assist Reprod Genet 34 1691-1698 2017b.

  • Carvalho LML Ferreira CN Candido AL Reis FM Soter MO Sales MD Silva IFO Nunes FC Gomes KB. Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome. Arch Gynecol Obstet 296 617-621 2017c.

  • Chang HM Klausen C Leung PCK. Antimullerian hormone inhibits follicle-stimulating hormone-induced adenylyl cyclase activation aromatase expression and estradiol production in human granulosa-lutein cells. Fertil Steril 100 585-592 2013.

  • Chen J Shen S Tan Y Xia D Cia Y Cao Y Cao Y Wang W Wu X Wang H Yi L Gao Q Wang Y. The correlation of aromatase activity and obesity in women with or without polycystic ovary syndrome. J Ovarian Res 22 11 2015.

  • Cimino I Casoni F Liu X. Novel role for anti-Mullerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nat Commun 7 10055 2016.

  • De Leo V Musacchio MC Cappelli V Massaro MG Morgante G Petraglia F. Genetic hormonal and metabolic aspects of PCOS: an update. Reprod Biol Endocrinol 14 38 2016.

  • Deligeoroglou E Vrachnis N Athanasopoulos N Iliodromiti Z Sifakis S Iliodromiti S Siristatidis C Creatsas G. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol 28 974-978 2012.

  • Delitala AP Capobianco G Delitala G Cherchi PL Dessole S. Polycystic ovary syndrome adipose tissue and metabolic syndrome. Arch Gynecol Obstet 296 405-419 2017.

  • Deswal R Yadav A Dang AS. Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis. Syst Biol Reprod Med 64 12-24 2018.

  • Diamanti-Kandarakis E Papavassiliou AG Kandrarakis SA Chrousos GP. Focus on Polycystic Ovary Syndrome pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 19 280-285 2007.

  • Di Segni C Silvestrini A Fato R Bergamini C Guidi F Raimondo S Meucci E Romualdi D Apa R Lanzone A Mancini A. Plasmatic and intracellular markers of oxidative stress in normal weight and obese patients with Polycystic Ovary Syndrome. Exp Clin Endocrinol Diabetes 125 506-513 2017.

  • Duleba AJ Dokras A. Is PCOS an inflammatory process? Fertil Steril 97 7-12 2012.

  • Dumesic DA Akopians AL Madrigal VK. Hyperandrogenism accompanies increased intra-abdominal fat storage in normal weight Polycystic Ovary Syndrome women. J Clin Endocrinol Metab 101 4178-4188 2016.

  • Dumont A Robin G Catteau-Jonard S Dewailly D. Role of anti-Mullerian hormone in pathophysiology diagnosis and treatment of Polycystic Ovary Syndrome: a review. Reprod Biol Endocrinol 13 137 2015.

  • Dunaif A. Perspectives in Polycystic Ovary Syndrome: From hair to eternity. J Clin Endocrinol Metab 101 759-768 2016.

  • Echiburu B Perez-Bravo F Galgani JE Sandoval D Saldias C Crisosto N Maliqueo M Sir-Petermann T. Enlarged adipocytes in subcutaneous adipose tissue associated to hyperandrogenism and visceral adipose tissue volume in women with polycystic ovary syndrome. Steroids 130 15-21 2018.

  • Eder K Baffy N Falus A Fulop AK. The major inflammatory mediator interleukin-6 and obesity. Inflamm Res 58 727-736 2009.

  • Escobar-Morreale HF San Millan JL. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 18 266-272 2007.

  • Faghfoori Z Fazelian S Shadnoush M Goodarzi R. Nutritional management in women with polycystic ovary syndrome: A review study. Diabetes Metab Syndr 11 429-432 2017.

  • Fan W Li S Chen Q Huang Z. Association between the (TAAAA)n SHBG polymorphism and PCOS: a systematic review and meta-analysis. Gynecol Endocrinol 29 645-650 2013.

  • Fonseca-Alaniz MH Takada J Alonso-Vale MI Lima FB. Adipose tissue as an endocrine organ: from theory to practice. J Pediatr 83 192-203 2007.

  • Foroozanfard F Jamilian M Bahmani F Talaee R Talaee N Hashmi T Nasri K Asemi Z Esmaillzadeh A. Calcium plus vitamin D supplementation influences biomarkers of inflammation and oxidative stress in overweight and vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Clin Endocrinol 83 888-894 2015.

  • Ghafurniyan H Azarnia M Nabiuni M Karimzadeh L. The effect of green tea extract on reproductive improvement in estradiol valerate-induced polycystic ovary Polycystic Ovarian Syndrome in rat. Iran J Pharm Res 14 1215-1233 2015.

  • Glintborg D Andersen M. Management of endocrine disease: morbidity in polycystic ovary syndrome. Eur J Endocrinol 176 R53-R65 2017.

  • Gonzalez F Rote NS Minium J Kirwan JP. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 91 336-340 2006.

  • Gonzalez F Kirwan JP Rote NS Minium J. Elevated circulating levels of tissue factor in polycystic ovary syndrome. Clin Appl Thromb Hemost 19 66-72 2013.

  • Goodarzi MO Shah NA Antoine HJ Pall M Guo X Azziz R. Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab 91 4085-4091 2006.

  • Green A Rumberger JM Stuart CA Ruhoff MS. Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is glucose dependent: implications for long-term regulation of lipolysis. Diabetes 53 74-81 2004.

  • Groth SW. Adiponectin and polycystic ovary syndrome. Biol Res Nurs 12 62-72 2010.

  • Hosseini AH Kohan L Aledavood A Rostami S. Association of miR-146a rs2910164 and miR-222 rs2858060 polymorphisms with the risk of polycystic ovary syndrome in Iranian women: A case-control study. Taiwan J Obstet Gynecol 56 652-656 2017.

  • Insenser M Martinez-Garcia MA San-Milan JL Escobar-Morreale HF. Proteomic analysis of plasma in the Polycystic Ovary Syndrome identifies novel markers involved in iron metabolism Acute-Phase Response and Inflammation. J Clin Endocrinol Metab 95 3863-3870 2010.

  • Insenser M Escobar-Morreale. Proteomics and polycystic ovary syndrome. Expert Rev Proteomics 10 435-447 2013.

  • Jayasena C Franks S. The management of patients with polycystic ovary syndrome. Nature Reviews Endocrinology 10 624-636 2014.

  • Jakimiuk AJ Weitsman SR Magoffin DA. 5alpha-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 84 2414-2418 1999.

  • Jalilian A Kiani F Sayehmiri F Sayehmiri K Khodaee Z Akbari M. Prevalence of polycystic ovary syndrome and its associated complications in Iranian women: A meta-analysis. Iran J Reprod Med 13 591-604 2015.

  • Jia H Yu L Guo X Gao W Jiang Z. Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis. Endocrine 42 299-306 2012.

  • Jiao J Fang Y Wang T Wang Z Zhuou M Wang X. Epidemiologic investigation of polycystic ovarian syndrome (PCOS) in Han ethnic women of reproductive age in Liaoning Province China. Clin Exp Obstet Gynecol 41 304-309 2014.

  • Joham AE Teede HJ Ranasinha S Zoungas S Boyele J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Womens Health (Larchmt) 24 299-307 2015.

  • Kahsar-Miller M Azziz R. The development of the polycystic ovary syndrome: family history as a risk factor. Trends Endocrinol Metab 9 55-58 1998.

  • Karakas SE. New biomarkers for diagnosis and management of polycystic ovary syndrome. Clin Chim Acta. 471 248-253 2017.

  • Koiou E Tziomalos K Katsikis I Dinas K Tsourdi EA Delkos D Papadakis E Panidis D. Plasma Von Willebrand factor antigen levels are elevated in the classic phenotypes of polycystic ovary syndrome. Hormones 11 77-85 2012.

  • Kopelman PG. Obesity as a medical problem. Nature 404 635-643 2000.

  • Kristiansen SB Endoh A Casson PR Buster JE Hornsby PJ. Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. Steroids 62 258-265 1997.

  • Kurobe FMC Dzik A Cavagna M Drezett J. Importancia do hormonio anti-Mullerian on a infertilidade. Reprod Clim 27 104-108 2012.

  • Lamanna C Monami M Marchionni N Mannucci EE. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 13 221-228 2011.

  • Langin D. Control of fatty acid and glycerol release in adipose tissue lipolysis. C R Biol 329 598-607 2006.

  • Lehr S Hartwig S Sell H. Adipokines: A treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 6 91-101 2012.

  • Liu Y Nair MG. An efficient and economical MTT assay for determining the antioxidant activity of plant natural product extracts and pure compounds. J Nat Prod 73 1193-1195 2010.

  • Liu H Zhao H Chen ZJ. Genome-wide association studies for Polycystic Ovary Syndrome. Semin Reprod Med 34 224-229 2016.

  • Mackman N. The role of tissue factor and factor VIIa in hemostasis. Anesth Analg 108 1447-1452 2009.

  • Macut D Damjanovic S Panidis D Spanos N Glisic B Petakov M Rousso D Kourtis A Bjekic J Milic N. Oxidised low-density lipoprotein concentration - early marker of an altered lipid metabolism in young women with PCOS. Eur J Endocrinol 155 131-136 2006.

  • Macut D Bjekic-Macut J Savic-Radojevic A. Dyslipidemia and oxidative stress in PCOS. Front Horm Res 40 51-63 2013.

  • Magoffin DA. Ovarian theca cell. Int J Biochem Cell Biol 37 1344-1349 2005.

  • Mahde A Shaker M Al-Mashhadani Z. Study of Omentin1 and Other Adipokines and Hormones in PCOS Patients. Oman Med J 24 108-18 2009.

  • Maliqueo M Sun M Johansson J Benrick A Labrie F Svensson H Lonn M Duleba AJ Stener-Victorin E. Continuous administration of a P450 aromatase inhibitor induces Polycystic Ovary Syndrome with a metabolic and endocrine phenotype in female rats at adult age. Endocrinology 154 434-445 2013.

  • Manneras-Holm L Baghaei F Holm G Janson PO Ohlsson C Lonn M Stener-Victorin E. Coagulation and fibrinolytic disturbances in women with polycystic ovary syndrome. J Clin Endocrinol Metab 96 1068-1076 2011.

  • Matharoo-Ball B Hughes C Lancashire L Tooth D Ball G Creaser C Elgasim M Rees R Layfield R Atiomo W. Characterization of biomarkers in polycystic ovary syndrome (PCOS) using multiple distinct proteomic platforms. J Proteome Res 6 3321-3328 2007.

  • Mesri M Altieri DC. Endothelial cell activation by leukocyte microparticles. J Immunol 161 4382-4387 1998.

  • Miller VM Lahr BD Bailey KR Hodis HN Mulvagh SL Jayachandran M. Specific cell-derived microvesicles: Linking endothelial function to carotid artery intima-media thickness in low cardiovascular risk menopausal women. Atherosclerosis 246 24-28 2016.

  • Mirza SS Shafique K Shaikh AR Khan NA Anwar Qureshi M. Association between circulating adiponectin levels and polycystic ovarian syndrome. J Ovarian Res 7 18 2014.

  • Mombaini E Jafarirad S Husain D Haghighizadeh MH Padfar P. The impact of green tea supplementation on anthropometric indices and inflammatory cytokines in women with Polycystic Ovary Syndrome. Phytother Res 31 747-754 2017.

  • Moran LJ Hutchison SK Meyer C Zoungas S Teede HJ. A comprehensive assessment of endothelial function in overweight women with and without polycystic ovary syndrome. Clin Sci 116 761-770 2009.

  • Morgante G Cappelli V Di Sabatino A Massaro MG De Leo V. Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association. Minerva Ginecol 67 457-463 2015.

  • Mortada R Kallail KJ Dong F Karakas S. HbA1c in Patients with Polycystic Ovary Syndrome: A Potential Marker of Inflammation. J Reprod Infertil 16 203-206 2015.

  • Murri M Luque-Ramirez M Insenser M Ojeda-Ojeda M Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 19 268-288 2013.

  • Musmar S Afaneh A Mo’alla H. Epidemiology of polycystic ovary syndrome: a cross sectional study of university students at An-Najah national university-Palestine. Reprod Biol Endocrinol 11 47 2013.

  • Nahum R Thong KJ Hillier SG. Metabolic regulation of androgen production by human thecal cells in vitro. Hum Reprod 10 75-81 1995.

  • National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106 3143-3421 2002.

  • Nestler JE Powers LP Matt DW Steingold KA Plymate SR Rittmaster RS Clore JN Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 72 83-89 1991.

  • Nielsen S Karpe F. Determinants of VLDL-triglycerides production. Curr Opin Lipidol 29 321-326 2012.

  • Norman RJ Dewailly D Legro RS Hickey TE. Polycystic ovary syndrome. Lancet 370 385-397 2007.

  • Ouchi N Parker JL Lugus JJ Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11 85-97 2011.

  • Ozer A Bakacak M Kıran H Ercan O Kostu B Kanat-Pektaş M Kilinc M Aslan F. Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome. Ginekol Pol 87 733-738 2016.

  • Palomba S Falbo SSA La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health 7 745-763 2015.

  • Papadakis G Kandaraki E Papalou O Vryonidou A Diamanti-Kandarakis E. Is cardiovascular risk in women with PCOS a real risk? Current insights. Minerva Endocrinol 42 340-355 2017.

  • Pavaleanu I Gafitanu D Popovici D Duceac LD Pavaleanu M. Treatment of metabolic alterations in Polycystic Ovary Syndrome. Rev Med Chir Soc Med Nat Iasi 120 258-263 2016.

  • Peng Z Sun Y Lv X Zhang H Liu C Dai S. Interleukin-6 levels in women with Polycystic Ovary Syndrome: A systematic review and meta-analysis. PLoS One 11 e0148531 2016.

  • Quinn MM Kao CN Ahmad AK Haisenleder DJ Santoro N Eisenberg E Legro RS Cedars MI Huddleston HG. Age-stratified thresholds of anti-Mullerian hormone improve prediction of polycystic ovary syndrome over a population-based threshold. Clin Endocrinol 87 733-740 2017.

  • Razavi M Jamilian M Karamali M Bahmani F Aghadovod E Asemi Z. The effects of vitamin D-K-calcium co-supplementation on endocrine inflammation and oxidative stress biomarkers in vitamin D-deficient women with polycystic ovary syndrome: a randomized double-blind placebo-controlled trial. Horm Metab Res 48 446-451 2016.

  • Reddy TV Govatati S Deenadayal M Shivaji S Bhanoori M. Polymorphisms in the TFAM and PGC1-α genes and their association with polycystic ovary syndrome among South Indian women. Gene 641 129-136 2018.

  • Reis GVOP Gontijo NA Rodrigues KF Alves MT Ferreira CN Gomes KB. Vitamin D receptor polymorphisms and the polycystic ovary syndrome: A systematic review. J Obstet Gynaecol Res 43 436-446 2017.

  • Repaci A Gambineri A Pasquali R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335 30-41 2011.

  • Rittmaster RS Deshwal N Lehman L. The role of adrenal hyperandrogenism insulin resistance and obesity in the pathogenesis of polycystic ovarian syndrome. J Clin Endocrinol Metab 76 1295-1300 1993.

  • Rocha MP Maranhao RC Maranhao RC Seydell TM Barcellos CRG Baracat EC Hayashida SAY Bydlowski SP Marcondes JAM. Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome. Fertil Steril 93 1948-1956 2010.

  • Rojas J Chavez M Olivar L Rojas M Morillo J Mejias J Calvo M Bermudez V. Polycystic ovary syndrome insulin resistance and obesity: navigating the pathophysiologic labyrinth. Int J Reprod Med 2014 719050 2014.

  • Rosenfield RL Ehrmann DA. The pathogenesis of Polycystic Ovary Syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 37 467-520 2016.

  • Ruan Y Ma J Xie X. Association of IRS-1 and IRS-2 genes polymorphisms with polycysticovary syndrome: a metaanalysis. Endocr J 59 601-619 2012.

  • Sales MF Soter MO Candido AL Fernandes AP Oliveira FR Ferreira ACS Souza MO Ferreira CN Gomes KB. Correlation between plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphism and metabolic/ proinflammatory factors in polycystic ovary syndrome. Gynecol Endocrinol 29 936-939 2013.

  • Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag 3 69-73 2007.

  • Santos LC Torrent IF. O tecido adiposo e a producao de adipocinas. Synthesis Revista Digital FAPAM 2 110-119 2010.

  • Sarray S Madan S Saleh LR Mahmoud N Almawi WY. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertil Steril 104 460-466 2015.

  • Seyfart T Friedrich N Kische H Bulow R Wallaschofski H Volzke H Nauck M Keevil BG Haring R. Association of sex hormones with physical laboratory and imaging markers of anthropometry in men and women from the general population. PLoS One 13 e0189042 2018.

  • Shen CC Yang AC Hung J Hu LY Tsai SJ. A nationwide population-based retrospective cohort study of the risk of uterine ovarian and breast cancer in women with polycystic ovary syndrome. Oncologist 20 45-49 2015.

  • Silva FS Soter MO Sales MF Candido AL Reis FM Silva IFO Souza MO Ferreira CN Gomes KB. Estrogen receptor α lpha gene (ESR1) Pvu II and Xba I polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome. Gene 560 44-49 2015.

  • Skalba P Dabkowska-Huc A Kazimierczak W Samojedny A Samojedny MP Chelmicki Z. Content of 5-alphareductase (type 1 and type 2) mRNA in dermal papillae from the lower abdominal region in women with hirsutism. Clin Exp Dermatol 31 564-570 2006.

  • Song GJ Kim SM Park KH Kim J Choi I Cho KH. SR-BI mediates high density lipoprotein (HDL)-induced antiinflammatory effect in macrophages. Biochem Biophys Res Commun 457 112-118 2015.

  • Soter MO Ferreira CN Sales MF Candido AL Reis FM Milagres KS Ronda C Silva IO Sousa MO Gomes KB. Peripheral blood-derived cytokine gene polymorphisms and metabolic profile in women with polycystic ovary syndrome. Cytokine 76 227-235 2015.

  • Spritzer PM Poy M Wiltgen D Mylius LS Capp E. Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal metabolic and anthropometric measurements. Hum Reprod 16 1340-1346 2001.

  • Targuer G Zoppini G Bonora E Moghetti P. Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome. Semin Thromb Hemost 40 600-618 2014.

  • Tata B Mimouni NEH Barbotin AL Malone SA Loyens A Pigny P Dewailly D Catteau-Jonard S Sundstrom- Poromaa I Piltonen TT Dal Bello F Medana C Prevot V Clasadonte J Giacobini P. Elevated prenatal anti- Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nat Med 24 834-846 2018.

  • Tehrani FR Simbar M Tohidi M Hosseinpanah F Azizi F. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Reprod Biol Endocrinol 9 39 2011.

  • Thathapudi S Kodati V Raj AY Addepallyn U Katragadda A Hasan Q. Role of TNF α in the etiopathogenesis of PCOS: a clinical biochemical and molecular genetic study. Mol Cytogenet 7 94 2014.

  • Unluturk U Sezgin E Yildiz BO. Evolutionary determinants of polycystic ovary syndrome-part 1. Fertil Steril 106 33-41 2016.

  • Van-Hall G Stennsberg A Sacchetti M Fischer C Keeller C Schjerling P Hiscock N Moller K Saltin B Febbraio MA Pedersen BK. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 88 3005-3010 2003.

  • Vassiliadi DA Barber TM Hughes BA McCarthy MI Wass JA Franks S Nightingale P Tomlinson JW Arlt W Stewart PM. Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. J Clin Endocrinol Metab 94 3558-3566 2009.

  • Vink JM Ssadzadeh S Lambalk CB Boomsma DI. Heritability of Polycystic Ovary Syndrome in a Dutch Twin- Family Study. J Clin Endocrinol Metab 91 2100-2104 2006.

  • Vodo S Bechi N Petroni A Muscoli C Aloisi AM. Testosterone-induced effects on lipids and inflammation. Mediators Inflamm 2013 1-8 2013.

  • Vrbikova J Dvorakova K Hill M Vcelak J Stanicka S Vankova M Sramkova D Vondra K Bendlova B Starka L. Determinants of circulating adiponectin in women with polycystic ovary syndrome. Gynecol Obstet Invest 60 155-161 2005.

  • Vural P Degirmencioglu S Saral NY Akgul C. Tumor necrosis factor alpha (-308) interleukin-6 (-174) and interleukin- 10 (-1082) gene polymorphisms in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 150 61-65 2010.

  • Wang Y Ng MC So WY Ma R Ko GT Tong PC Chan JC. Association between tumour necrosis factor-alpha G- 308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients. Nephrol Dial Transplant 20 2733-2738 2005.

  • Wellen KE Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112 1785-1788 2013.

  • Wilson AG Symons JA McDowell TL McDevitt HO Duff GW. Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation. Proc Natl Acad Sci USA 94 3195-3199 1997.

  • Wojta J. Platelet-derived microparticles in patients with high cardiovascular risk and subclinical atherosclerosis. Thromb Haemost 114 1099 2015.

  • Xavier LB Soter MO Sales MF Oliveira DKD Reis HJ Candido AL Reis FM Silva IO Gomes KB Ferreira CN. Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome. Gene 644 129-136 2018.

  • Xu X Du C Zheng Q Peng L Sun Y. Effect of metformin on serum interleukin-6 levels in polycystic ovary syndrome: a systematic review. BMC Womens Health 14 93 2014.

  • Zhang HH Halbleib M Ahmad F Manganiello VC Greenberg AS. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51 2929-2935 2002.

  • Zhao JL Chen ZJ Zhao LX Geng L Wang S Gao SS Zhang P Liu S Zhou FR. [Epidemiological study of clinical characteristics of Chinese Han ethnic women with polycystic ovary syndrome]. Zhonghua Fu Chan Ke Za Zhi 41 375-379 2006. [Article in Chinese].

  • Zhao H Lv Y Li L Chen ZJ. Genetic studies on Polycystic Ovary Syndrome. Best Pract Res Clin Obstet Gynaecol 37 56-65 2016.

  • Zheng SH Li XL. Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS. Gynecol Endocrinol 32 177-183 2016.

  • Zuo T Zhu M Xu W. Roles of oxidative stress in Polycystic Ovary Syndrome and cancers. Oxid Med Cell Longev 2016 8589318 2016.

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