Skip to main content
SpringerLink
Log in

Novel inflammatory markers in overweight women with and without polycystic ovary syndrome and following pharmacological intervention

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities. Aim: The aim of this study was to assess novel inflammatory markers [adipokines leptin, adiponectin, and leptin-adiponectin ratio (L/A)] in overweight women with and without PCOS and to examine alterations in these markers [aldosterone, leptin, adiponectin, and L/A] with pharmacological interventions modulating insulin resistance (IR) in PCOS. Materials/subjects and methods: Overweight age, and body mass index (BMI)-matched women with (no.=80) or without PCOS (no.=27) were assessed cross-sectionally. Subjects with PCOS were then randomised to 6 months metformin (1 g b.d, no.=26) or oral contraceptive pill (OCP) (35 g ethinyl estradiol/2 mg cytoproterone acetate, no.=30). Outcome measures were leptin, adiponectin, L/A, aldosterone, highly sensitive C-reactive protein, lipid profile, IR, and androgen levels. Results: Leptin levels were lower (156.4±85.9 vs 208.5±105.2 ng/ml, p=0.015) while adiponectin and L/A were not different between women with and without PCOS. Following intervention, IR increased for the OCP and decreased for metformin, however leptin and aldosterone decreased equivalently with the OCP and metformin with no difference between each treatment (p=0.583 and p=0.801, respectively). There was no change in adiponectin or L/A with the OCP or metformin. On multiple regression, the only baseline predictor of leptin was BMI (r2=0.485, p<0.001) and the strongest predictor of change in leptin was change in weight (r2=0.402, p<0.001). Conclusions: Alterations in leptin between women with and without PCOS and following pharmacological interventions are primarily related to adiposity and not IR. Aldosterone was reduced equivalently with metformin and the OCP despite differential effects on IR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Shaw LJ, Bairey Merz CN, et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health—National Heart, Lung, and Blood Institute sponsored Women’s Ischemia Syndrome Evaluation. J Clin Endocrinol Metab 2008, 93: 1276–84.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Meyer C, McGrath BP, Teede HJ. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. J Clin Endocrinol Metab 2005, 90: 5711–6.

    Article  PubMed  CAS  Google Scholar 

  3. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999, 84: 165–9.

    PubMed  CAS  Google Scholar 

  4. Diamanti-Kandarakis E, Paterakis T, Kandarakis HA. Indices of low-grade inflammation in polycystic ovary syndrome. Ann N Y Acad Sci 2006, 1092: 175–86.

    Article  PubMed  CAS  Google Scholar 

  5. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006, 116: 1784–92.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1 RA in human leukocytes. Biochem Biophys Res Commun 2004, 323: 630–5.

    Article  PubMed  CAS  Google Scholar 

  7. Gualillo O, Gonzalez-Juanatey JR, Lago F. The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trends Cardiovasc Med 2007, 17: 275–83.

    Article  PubMed  CAS  Google Scholar 

  8. Oda N, Imamura S, Fujita T, et al. The ratio of leptin to adiponectin can be used as an index of insulin resistance. Metabolism 2008, 57: 268–73.

    Article  PubMed  CAS  Google Scholar 

  9. Kumagai S, Kishimoto H, Masatakasuwa, Zou B, Harukasasaki. The leptin to adiponectin ratio is a good biomarker for the prevalence of metabolic syndrome, dependent on visceral fat accumulation and endurance fitness in obese patients with diabetes mellitus. Metab Syndr Relat Disord 2005, 3: 85–94.

    Article  PubMed  CAS  Google Scholar 

  10. Satoh N, Naruse M, Usui T, et al. Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004, 27: 2488–90.

    Article  PubMed  CAS  Google Scholar 

  11. Callera GE, Touyz RM, Tostes RC, et al. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension 2005, 45: 773–9.

    Article  PubMed  CAS  Google Scholar 

  12. Fejes-Toth G, Naray-Fejes-Toth A. Early aldosterone-regulated genes in cardiomyocytes: clues to cardiac remodeling? Endocrinology 2007, 148: 1502–10.

    Article  PubMed  CAS  Google Scholar 

  13. Ingelsson E, Pencina MJ, Tofler GH, et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study. Circulation 2007, 116: 984–92.

    Article  PubMed  CAS  Google Scholar 

  14. Giallauria F, Palomba S, De Sio I, et al. Inflammatory markers and visceral fat are inversely associated with maximal oxygen consumption in women with polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2009, 70: 394–400.

    Article  CAS  Google Scholar 

  15. Tarkun I, Arslan BC, Canturk Z, Turemen 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: 5592–6.

    Article  PubMed  CAS  Google Scholar 

  16. Atamer A, Demir B, Bayhan G, Atamer Y, Ilhan N, Akkus Z. Serum levels of leptin and homocysteine in women with polycystic ovary syndrome and its relationship to endocrine, clinical and metabolic parameters. J Int Med Res 2008, 36: 96–105.

    Article  PubMed  CAS  Google Scholar 

  17. Brzechffa PR, Jakimiuk AJ, Agarwal SK, Weitsman SR, Buyalos RP, Magoffin DA. Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1996, 81: 4166–9.

    PubMed  CAS  Google Scholar 

  18. 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: 4609–14.

    Article  PubMed  CAS  Google Scholar 

  19. Carmina E, Orio F, Palomba S, et al. Endothelial dysfunction in PCOS: role of obesity and adipose hormones. Am J Med 2006, 119: 356.e1-6.

    Article  PubMed  Google Scholar 

  20. Cascella T, Palomba S, Tauchmanovà L, et al. Serum aldosterone concentration and cardiovascular risk in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2006, 91: 4395–400.

    Article  PubMed  CAS  Google Scholar 

  21. Spranger J, Mohlig M, Wegewitz U, et al. Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2004, 61: 738–46.

    Article  CAS  Google Scholar 

  22. Xita N, Papassotiriou I, Georgiou I, Vounatsou M, Margeli A, Tsatsoulis A. The adiponectin-to-leptin ratio in women with polycystic ovary syndrome: relation to insulin resistance and proin-flammatory markers. Metabolism 2007, 56: 766–71.

    Article  PubMed  CAS  Google Scholar 

  23. Meyer C, McGrath BP, Teede HJ. Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome. Diabetes Care 2007, 30: 471–8.

    Article  PubMed  CAS  Google Scholar 

  24. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–9.

    Article  PubMed  CAS  Google Scholar 

  25. Wolever TM, Jenkins DJ, Jenkins AL, Josse RG. The glycemic index: methodology and clinical implications. Am J Clin Nutr 1991, 54: 846–54.

    PubMed  CAS  Google Scholar 

  26. Pearson TA, Mensah GA, Alexander RW, et al; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003, 107: 499–511.

    Article  PubMed  Google Scholar 

  27. Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS. Metformin versus ethinyl estradiolcyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2003, 88: 148–56.

    Article  PubMed  CAS  Google Scholar 

  28. Moran LJ, Noakes M, Clifton PM, Wittert GA, Belobrajdic DP, Norman RJ. C-reactive protein before and after weight loss in overweight women with and without polycystic ovary syndrome. J Clin Endocrinol Metab 2007, 92: 2944–51.

    Article  PubMed  CAS  Google Scholar 

  29. Mohlig M, Spranger J, Osterhoff M, et al. The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol 2004, 150: 525–32.

    Article  PubMed  Google Scholar 

  30. 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 premenopausal women. Diabetologia 2003, 46: 625–33.

    PubMed  CAS  Google Scholar 

  31. Festa A, D’Agostino R Jr, Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000, 102: 42–7.

    Article  PubMed  CAS  Google Scholar 

  32. Barber TM, Golding SJ, Alvey C, et al. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008, 93: 999–1004.

    Article  PubMed  CAS  Google Scholar 

  33. Knudson JD, Dincer UD, Zhang C, et al. Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol 2005, 289: H48–56.

    Article  PubMed  CAS  Google Scholar 

  34. Loffreda S, Yang SQ, Lin HZ, et al. Leptin regulates proinflammatory immune responses. Faseb J 1998, 12: 57–65.

    PubMed  CAS  Google Scholar 

  35. Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature 1995, 377: 527–29.

    Article  PubMed  CAS  Google Scholar 

  36. Remsberg KE, Talbott EO, Zborowski JV, Evans RW, McHughPemu K. Evidence for competing effects of body mass, hyperinsulinemia, insulin resistance, and androgens on leptin levels among lean, overweight, and obese women with polycystic ovary syndrome. Fertil Steril 2002, 78: 479–86.

    Article  PubMed  Google Scholar 

  37. Pasquali R, Gambineri A, Biscotti D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000, 85: 2767–74.

    Article  PubMed  CAS  Google Scholar 

  38. Morin-Papunen LC, Koivunen RM, Tomás C, Ruokonen A, Martikainen HK. Decreased serum leptin concentrations during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998, 83: 2566–8.

    Article  PubMed  CAS  Google Scholar 

  39. Romualdi D, Campagna G, Selvaggi L Jr, et al. Metformin treatment does not affect total leptin levels and free leptin index in obese patients with polycystic ovary syndrome. Fertil Steril 2008, 89: 1273–6.

    Article  PubMed  CAS  Google Scholar 

  40. Krotkiewski M, Landin K, Dahlgren E, Janson PO, Holm G. Effect of two modes of antiandrogen treatment on insulin sensitivity and serum leptin in women with PCOS. Gynecol Obstet Invest 2003, 55: 88–95.

    Article  PubMed  CAS  Google Scholar 

  41. Chapman IM, Wittert GA, Norman RJ. Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters. Clin Endocrinol (Oxf) 1997, 46: 175–81.

    Article  CAS  Google Scholar 

  42. Pirwany IR, Fleming R, Sattar N, Greer IA, Wallace AM. Circulating leptin concentrations and ovarian function in polycystic ovary syndrome. Eur J Endocrinol 2001, 145: 289–94.

    Article  PubMed  CAS  Google Scholar 

  43. Mantzoros CS, Dunaif A, Flier JS. Leptin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab 1997, 82: 1687–91.

    PubMed  CAS  Google Scholar 

  44. Escobar-Morreale HF, Villuendas G, Botella-Carretero JI, et al. Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study. Hum Reprod 2006, 21: 2257–65.

    Article  PubMed  CAS  Google Scholar 

  45. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol 2004, 219: 9–15.

    Article  PubMed  CAS  Google Scholar 

  46. Carmina E, Chu MC, Moran C, Tortoriello D, Vardhana P, Tena G, Preciado R, Lobo R. Subcutaneous and omental fat expression of adiponectin and leptin in women with polycystic ovary syndrome. Fertil Steril 2008, 89: 642–8.

    Article  PubMed  CAS  Google Scholar 

  47. Vrbíková J, Dvoráková K, Hill M, et al. Determinants of circulating adiponectin in women with polycystic ovary syndrome. Gynecol Obstet Invest 2005, 60: 155–61.

    Article  PubMed  CAS  Google Scholar 

  48. Nishizawa H, Shimomura I, Kishida K, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 2002, 51: 2734–41.

    Article  PubMed  CAS  Google Scholar 

  49. Tan BK, Chen J, Digby JE, Keay SD, Kennedy CR, Randeva HS. Upregulation of adiponectin receptor 1 and 2 mRNA and protein in adipose tissue and adipocytes in insulin-resistant women with polycystic ovary syndrome. Diabetologia 2006, 49: 2723–8.

    Article  PubMed  CAS  Google Scholar 

  50. Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008, 93: 2670–8.

    Article  PubMed  CAS  Google Scholar 

  51. Ibáñez L, de Zegher F. Ethinylestradiol-drospirenone, flutamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism: opposite effects on adipocytokines and body adiposity. J Clin Endocrinol Metab 2004, 89: 1592–7.

    Article  PubMed  CAS  Google Scholar 

  52. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997, 18: 774–800.

    PubMed  CAS  Google Scholar 

  53. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003, 301: 1045–50.

    Article  PubMed  CAS  Google Scholar 

  54. Kotani K, Sakane N, Saiga K, Kurozawa Y. Leptin: adiponectin ratio as an atherosclerotic index in patients with type 2 diabetes: relationship of the index to carotid intima-media thickness. Diabetologia 2005, 48: 2684–6.

    Article  PubMed  CAS  Google Scholar 

  55. Dobbelsteyn CJ, Joffres MR, MacLean DR, Flowerdew G. A comparative evaluation of waist circumference, waist-to-hip ratio and body mass index as indicators of cardiovascular risk factors. The Canadian Heart Health Surveys. Int J Obes Relat Metab Disord 2001, 25: 652–61.

    Article  PubMed  CAS  Google Scholar 

  56. Weerakiet S, Bunnag P, Phakdeekitcharoen B, et al. Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: using the International Diabetes Federation criteria. Gynecol Endocrinol 2007, 23: 153–60.

    Article  PubMed  Google Scholar 

  57. Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension 2004, 43: 358–63.

    Article  PubMed  CAS  Google Scholar 

  58. Kraus D, Jager J, Meier B, Fasshauer M, Klein J. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res 2005, 37: 455–9.

    Article  PubMed  CAS  Google Scholar 

  59. Eguchi K, Tomizawa H, Ishikawa J, Hoshide S, Numao T, Fukuda T, Shimada K, Kario K. Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes. Hypertens Res 2007, 30: 23–30.

    Article  PubMed  CAS  Google Scholar 

  60. Dorella M, Giusto M, Da Tos V, et al. Improvement of insulin sensitivity by metformin treatment does not lower blood pressure of nonobese insulin-resistant hypertensive patients with normal glucose tolerance. J Clin Endocrinol Metab 1996, 81: 1568–74.

    PubMed  CAS  Google Scholar 

  61. Ohyama K, Fujimoto M, Nakagomi Y, Ohta M, Yamori T, Kato K. Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature. Horm Res 1991, 36: 216–9.

    Article  PubMed  CAS  Google Scholar 

  62. Takeda Y, Miyamori I, Yoneda T, et al. Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab 1996, 81: 2797–800.

    PubMed  CAS  Google Scholar 

  63. Szmuilowicz ED, Adler GK, Williams JS, et al. Relationship between aldosterone and progesterone in the human menstrual cycle. J Clin Endocrinol Metab 2006, 91: 3981–7.

    Article  PubMed  CAS  Google Scholar 

  64. Wunder DM, Yared M, Bersinger NA, Widmer D, Kretschmer R, Birkhäuser MH. Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women. Eur J Endocrinol 2006, 155: 137–42.

    Article  PubMed  CAS  Google Scholar 

  65. Galván RE, Basurto L, Saucedo R, Campos S, Hernández M, Zárate A. [Adiponectin concentrations during menstrual cycle]. Ginecol Obstet Mex 2007, 75: 435–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Jean Hailes Foundation for Women’s Health, Monash Institute of Health Services Research, Monash University, Monash Medical Centre, Locked bag 29, 246 Clayton Road, Clayton, Victoria, 3168, Australia

    L. J. Moran BSc (Hons), BND, PhD, S. K. Hutchison, S. Zoungas & H. J. Teede

  2. Diabetes Unit, Southern Health, Clayton, Victoria, Australia

    C. Meyer, S. Zoungas & H. J. Teede

Authors
  1. L. J. Moran BSc (Hons), BND, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. K. Hutchison
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Zoungas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. J. Teede
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. J. Moran BSc (Hons), BND, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moran, L.J., Meyer, C., Hutchison, S.K. et al. Novel inflammatory markers in overweight women with and without polycystic ovary syndrome and following pharmacological intervention. J Endocrinol Invest 33, 258–265 (2010). https://doi.org/10.1007/BF03345790

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345790

Key Words

Search

Navigation