Background/Aims: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities and carries a number of cardiovascular risk factors. Low-grade chronic inflammation has been thought to play a role in the pathogenesis of atherosclerosis and PCOS patients have an increased rate of subclinical inflammation. In the present study, considering the major role that hepcidin plays in the regulation of iron metabolism and as an inflammatory marker, we investigated hepcidin in PCOS patients and its role in predicting cardiovascular disease (CVD) development. Methods: Forty patients with PCOS and 40 age- and body mass index-matched healthy controls were included in the study. Iron metabolites, insulin resistance (IR), inflammatory markers and hepcidin levels were analyzed. Results: IR parameters, inflammatory markers, iron parameters and hepcidin levels were similar between the PCOS and control groups. While the inflammatory markers were significantly high in the overweight and obese PCOS subgroup, the hepcidin levels were also high but this elevation was not statistically significant. Conclusion: Obesity is the principle mechanism of chronic inflammation and IR in PCOS patients. C-reactive protein and interleukin-6 should be used to predict and follow the risk of CVD development in PCOS cases. Hepcidin may be used as an additional marker in the follow-up of PCOS patients in the future.

Keywords:
Polycystic ovary syndrome, Hepcidin, Cardiovascular disease, Obesity, Insulin resistance
1.
Seow KM, Juan CC, Wang PH, Ho LT, Hwang JL: Expression levels of vascular cell adhesion molecule-1 in young and nonobese women with polycystic ovary syndrome. Gynecol Obstet Invest 2012;73:236-241.
2.
Siebert TI, Viola MI, Steyn DW, Kruger TF: Is metformin indicated as primary ovulation induction agent in women with PCOS? A systematic review and meta-analysis. Gynecol Obstet Invest 2012;73:304-313.
3.
Vrbikova J, Fanta M, Cibula D, Vondra K, Bendlova B: Impaired glucose metabolism in women with polycystic ovary syndrome. Gynecol Obstet Invest 2009;68:186-190.
4.
Shroff R, Kerchner A, Maifeld M, Van Beek EJ, Jagasia D, Dokras A: Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab 2007;92:4609-4614.
5.
Blake GJ, Ridker PM: Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med 2002;252:283-294.
6.
Nakanishi T, Hasuike Y, Otaki Y Kida A, Nonoguchi H, Kuragano T: Hepcidin: another culprit for complications in patients with chronic kidney disease? Nephrol Dial Transplant 2011;26:3092-3100.
7.
Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-788.
8.
Park CH, Valore EV, Waring AJ, Ganz T: Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806-7810.
9.
Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, Iannelli A, Staccini-Myx A, Casanova D, Ben Amor I, Saint-Paul MC, Huet PM, Sadoul JL, Gugenheim J, Srai SK, Tran A, Le Marchand-Brustel Y: Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006;131:788-796.
10.
Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003;101:2461-2463.
11.
Fleming MD: The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology Am Soc Hematol Educ Program 2008;151-158.
12.
Kuragano T, Itoh K, Shimonaka Y Kida A, Furuta M, Kitamura R, Yahiro M, Nanami M, Otaki Y, Hasuike Y, Nonoguchi H, Nakanishi T: Hepcidin as well as TNF alpha are significant predictors of arterial stiffness in patients on maintenance hemodialysis. Nephrol Dial Transplant 2011;26:2663-2667.
13.
Valenti L, Dongiovanni P, Motta BM, Swinkels DW, Bonara P, Rametta R, Burdick L, Frugoni C, Fracanzani AL, Fargion S: Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular damage in patients with metabolic syndrome alterations. Arterioscler Thromb Vasc Biol 2011;31:683-690.
14.
Sullivan JL: Macrophage iron, hepcidin, and atherosclerotic plaque stability. Exp Biol Med (Maywood) 2007;232:1014-1020.
15.
Luque-Ramírez M, Álvarez-Blasco F, Alpañés M, Escobar-Morreale HF: Role of decreased circulating hepcidin concentrations in the iron excess of women with the polycystic ovary syndrome. J Clin Endocrinol Metab 2011;96:846-852.
16.
Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S: Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002;99:4596-4601.
17.
Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C: Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 2003;33:21-22.
18.
Escobar-Morreale HF, Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Sancho J, San Millán JL: Body iron stores are increased in overweight and obese women with polycystic ovary syndrome. Diabetes Care 2005;28:2042-2044.
19.
Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI, Sanchón R, San Millán JL, Escobar-Morreale HF: Increased body iron stores of obese women with polycystic ovary syndrome are a consequence of insulin resistance and hyperinsulinism and are not a result of reduced menstrual losses. Diabetes Care 2007;30:2309-2313.
20.
Le Guenno G, Chanseaume E, Ruivard M, Morio B, Mazur A: Study of iron metabolism disturbances in an animal model of insulin resistance. Diabetes Res Clin Pract 2007;77:363-370.
21.
Sanad M, Osman M, Gharib A: Obesity modulate serum hepcidin and treatment outcome of iron deficiency anemia in children: a case control study. Ital J Pediatr 2011;37:34.
22.
Wenzel BJ, Stults HB, Mayer J: Hypoferraemia in obese adolescents. Lancet 1962;2:327-328.
23.
Pinhas-Hamiel O, Newfield RS, Koren I, Agmon A, Lilos P, Phillip M: Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes Relat Metab Disord 2003;27:416-418.
24.
Greenberg AS, Obin MS: Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461-465.
25.
Escobar-Morreale HF, Villuendas G, Botella-Carretero JI, Sancho J, San Millán JL: Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. Diabetologia 2003;46:625-633.
26.
Möhlig M, Spranger J, Osterhoff M, Ristow M, Pfeiffer AF, Schill T, Schlösser HW, Brabant G, Schöfl C: The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol 2004;150:525-532.
27.
Orio F Jr, Palomba S, Cascella T, Di Biase S, Manguso F: The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. J Clin Endocrinol Metab2005;90:2-5.
28.
Chiu KM, Arnaud CD, Ju J, Mayes D, Bacchetti P, Weitz S, Keller ET: Correlation of estradiol, parathyroid hormone, interleukin-6, and soluble interleukin-6 receptor during the normal menstrual cycle. Bone 2000;26:79-85.
29.
Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N: Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001;86:2453-2455.
30.
Tarkun I, Arslan BC, Cantürk Z, Türemen E, Sahin T, Duman C: Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 2004;89:5592-5596.
31.
Diamanti-Kandarakis E, Paterakis T, Alexandraki K, Piperi C, Aessopos A, Katsikis I, Katsilambros N, Kreatsas G, Panidis D: Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 2006;21:1426-1431.
32.
Rajapurkar MM, Shah SV, Lele SS, Hegde UN, Lensing SY, Gohel K, Mukhopadhyay B, Gang S, Eigenbrodt ML: Association of catalytic iron with cardiovascular disease. Am J Cardiol 2012;109:438-442.
33.
Saeed O, Otsuka F, Polavarapu R, Karmali V, Weiss D, Davis T, Rostad B, Pachura K, Adams L, Elliott J, Taylor WR, Narula J, Kolodgie F, Virmani R, Hong CC, Finn AV: Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis. Arterioscler Thromb Vasc Biol 2012;32:299-307.
34.
Finn AV, Nakano M, Polavarapu R Karmali V, Saeed O, Zhao X, Yazdani S, Otsuka F, Davis T, Habib A, Narula J, Kolodgie FD, Virmani R: Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J Am Coll Cardiol 2012;59:166-177.
© 2013 S. Karger AG, Basel
2013
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