Skip to main content
SpringerLink
Log in

Clinical Features

  • Chapter
Metabolic Aspects of PCOS

  • 1320 Accesses

Abstract

Polycystic ovary syndrome (PCOS) is a chronic and self-perpetuating endocrine disorder, whose clinical, endocrine, and metabolic manifestations affect the whole life course of a patient. In PCOS, in fact, we can distinguish two sides of the same coin: endocrine and metabolic aspects.

Insulin resistance and the associated metabolic abnormalities are frequent findings in women with polycystic ovary syndrome. Many women with PCOS meet the criteria for the metabolic syndrome (MS), as they report a higher incidence of hypertension, dyslipidemia, and visceral obesity.

In fact, insulin resistance, and consequent compensatory hyperinsulinemia, appears to be the central pathophysiologic mechanism that links PCOS to its metabolic disorders. In this chapter, all the endocrine and metabolic features of PCOS are deeply described.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rebar R, Judd HL, Yen SS et al (1976) Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 57:1320–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hsueh AJW (1986) Paracrine mechanism involved in granulosa cell differentiation. Clin Endocrinol Metab 15:117–134

    Article  CAS  PubMed  Google Scholar 

  3. Erickson GF, Magoffin DA, Gabriel Garzo V et al (1992) Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum Reprod 7:293–299

    CAS  PubMed  Google Scholar 

  4. Mason HD, Willis DS, Beard RW et al (1994) Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid. J Clin Endocrinol Metab 79:1355–1360

    CAS  PubMed  Google Scholar 

  5. Hillier SG (1994) Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod 9:188–191

    CAS  PubMed  Google Scholar 

  6. Abbott DH, Dumesic DA, Franks S (2002) Developmental origin of polycystic ovary syndrome-hypothesis. J Endocrinol 174:1–5

    Article  CAS  PubMed  Google Scholar 

  7. Zawadzki JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome; towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, Merriam G (eds) Polycystic ovary syndrome. Blackwell Scientific, Boston, pp 377–384

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. Taylor AE, McCourt B, Martin KA et al (1997) Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab 82:2248–2256

    CAS  PubMed  Google Scholar 

  10. Azziz R, Task Force on the Phenotype of the Polycystic Ovary Syndrome of the Androgen Excess PCOS Society et al (2009) The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 91:456–488

    Article  PubMed  Google Scholar 

  11. Molli GW Jr, Rosenfield RL (1979) Testosterone binding and free plasma androgen concentrations under physiological conditions: characterization by flow dialysis technique. J Clin Endocrinol Metab 49:730–736

    Article  Google Scholar 

  12. Nestler JE, Powers LP, Matt DW et al (1991) 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

    Article  CAS  PubMed  Google Scholar 

  13. Yildiz BO, Azziz R (2007) The adrenal and polycystic ovary syndrome. Rev Endocr Metab Disord 8:331–342

    Article  CAS  PubMed  Google Scholar 

  14. Lachelin GC, Barnett M, Hopper BR et al (1979) Adrenal function in normal women and women with the polycystic ovary syndrome. J Clin Endocrinol Metab 49:892–898

    Article  CAS  PubMed  Google Scholar 

  15. Billing H, Furuta I, Hsueh AJW (1993) Estrogens inhibit and androgen enhance ovarian granulosa cell apoptosis. Endocrinology 133:2204–2212

    Google Scholar 

  16. Okutsu Y et al (2010) Exogenous androstenedione induces formation of follicular cysts and premature luteinization of granulosa cells in the ovary. Fertil Steril 93:927–935

    Article  CAS  PubMed  Google Scholar 

  17. Ciotta L, Stracquadanio M et al (2011) Effects of Myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 15:509–514

    CAS  PubMed  Google Scholar 

  18. DeVane GW, Czekala NM, Judd HL, Yen SS (1975) Circulating gonadotropins, estrogens, and androgens in polycystic ovarian disease. J Obstet Gynecol 121:496–500

    CAS  Google Scholar 

  19. Baird DT, Corker CS, Davidson DW et al (1977) Pituitary-ovarian relationships in polycystic ovary syndrome. J Clin Endocrinol Metab 45:798–801

    Article  CAS  PubMed  Google Scholar 

  20. MacDonald PC, Rombaut RP, Siiteri PK (1976) Plasma precursors of estrogen. Extent of conversion of plasma δ-4-androstenedione to estrone in normal males and nonpregnant normal, castrate and adrenalectomized females. J Clin Endocrinol Metab 27:1103–1111

    Article  Google Scholar 

  21. Shen ZQ, Zhu HT, Lin JF (2008) Reverse of progestin-resistant atypical endometrial hyperplasia by metformin and oral contraceptives. Obstet Gynecol 112:465–467

    Article  PubMed  Google Scholar 

  22. Savaris RF, Groll JM, Young SL et al (2011) Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles. J Clin Endocrinol Metab 96:1737–1746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Margarit L, Taylor A, Roberts MH et al (2010) MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab 95:5320–5329

    Article  CAS  PubMed  Google Scholar 

  24. Li X, Feng Y, Lin JF et al (2014) Endometrial progesterone resistance and PCOS. J Biomed Sci 21:2–8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Lee MM, Donahoe PK, Hasegawa T et al (1996) Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol 81:571–576

    CAS  Google Scholar 

  26. Cook CL, Siow Y, Taylor S, Fallat M (2000) Serum mullerian inhibiting substance levels during normal menstrual cycles. Fertil Steril 73:859–861

    Article  CAS  PubMed  Google Scholar 

  27. Weenen C, Laven JS, Von Bergh AR et al (2004) Anti-mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 10:77–83

    Article  CAS  PubMed  Google Scholar 

  28. Durlinger AL, Gruijters MJ, Kramer P et al (2002) Anti-mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 143:1076–1084

    CAS  PubMed  Google Scholar 

  29. Durlinger AL, Visser JA, Themmen AP (2002) Regulation of ovarian function: the role of anti-mullerian hormone. Reproduction 124:601–609

    Article  CAS  PubMed  Google Scholar 

  30. Fallat ME, Siow Y, Marra M et al (1997) Mullerian inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome and endometriosis. Fertil Steril 67:962–965

    Article  CAS  PubMed  Google Scholar 

  31. Cook C, Siow Y, Bremer AG, Fallat ME (2002) Relation between mullerian inhibiting substance and other reproductive hormones in untreated women with PCOS and normal women. Fertil Steril 77:141–146

    Article  PubMed  Google Scholar 

  32. Jonard S, Dewailly D (2004) The follicular excess in polycystic ovaries, due to ovarian hyperandrogenism, may be the culprit for the follicular arrest. Hum Reprod Update 10:107–117

    Article  PubMed  Google Scholar 

  33. Sahmay S, Aydin Y, Atakul N et al (2014) Relation of antimullerian hormone with the clinical signs of hyperandrogenism and polycystic ovary morphology. Gynecol Endocrinol 30(2):130–134

    Article  CAS  PubMed  Google Scholar 

  34. Pellat L, Rice S, Mason HD (2010) Anti-mullerian hormone and polycystic ovary syndrome: a mountain too high? Reproduction 139:825–833

    Article  CAS  Google Scholar 

  35. Xi W, Gong F, Lu G (2012) Correlation of serum anti-mullerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients. J Assist Reprod Genet 29:397–402

    Article  PubMed  PubMed Central  Google Scholar 

  36. Piouka A, Farmakiotis D, Katsikis I et al (2009) Anti-mullerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels. Am J Physiol Endocrinol Metab 296:E238–E243

    Article  CAS  PubMed  Google Scholar 

  37. Febregues F, Castelo-Branco C, Carmona F et al (2011) The effect of different hormone therapies on anti-mullerian hormone serum levels in anovulatory women of reproductive age. Gynecol Endocrinol 27:216–224

    Article  CAS  Google Scholar 

  38. Dewailly D, Pigny P, Soudan B et al (2010) Reconciling the definitions of polycystic ovary syndrome: the ovarian follicle number and serum anti-mullerian hormone concentrations aggregate with the markers of hyperandrogenism. J Clin Endocrinol Metab 95:4399–4405

    Article  CAS  PubMed  Google Scholar 

  39. Caglar GS, Kayaouglu I, Pabuccu R et al (2013) Anti-mullerian hormone and insulin resistance in classic phenotype lean PCOS. Arch Gynecol Obstet 288:905–910

    Article  CAS  PubMed  Google Scholar 

  40. Rojas J, Chavez M, Olivar L et al (2014) Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int J Reprod Med. http://dx.doi.org/10.1155/2014/719050

  41. Brassard M, AinMelk Y, Baillargeon JP (2008) Basic infertility including polycystic ovary syndrome. Med Clin North Am 92:1163–1192

    Article  CAS  PubMed  Google Scholar 

  42. Brower M, Brennan K, Pall M, Azziz R (2013) The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS. J Clin Endocrinol Metab 98(12):E1967–E1971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Strowitzki T, Capp E, von Eye CH (2010) The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients. Eur J Obstet Gynecol Reprod Biol 149:178–181

    Article  CAS  PubMed  Google Scholar 

  44. Chittenden BG, Fullerton G, Maheswari A, Bhattacharya S (2009) Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online 19:398–405

    Article  CAS  PubMed  Google Scholar 

  45. Hardiman P, Pillay OC, Atiomo W (2003) Polycystic ovary syndrome and endometrial carcinoma. Lancet 361:1810–1812

    Article  PubMed  Google Scholar 

  46. Teede H, Deeks A, Moran L (2010) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 8(41):1741–7015

    Google Scholar 

  47. Chakraborty P, Goswami SK, Rajani S et al (2013) Recurrent pregnancy loss in polycystic ovary syndrome: role of hyperhomocysteinemia and insulin resistance. PLoS One 8:e64446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kalra S et al (2013) Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the society for assisted reproductive technology registry to assess the impact of reproductive aging on live-birth rate. Fertil Steril 100:208–213

    Article  PubMed  Google Scholar 

  49. Redmond GP, Bergfeld WF (1990) Diagnostic approach to androgen disorders in women: acne, hirsutism, and alopecia. Cleve Clin J Med 57:423–427

    Article  CAS  PubMed  Google Scholar 

  50. Uno H (1986) Biology of hair growth. Semin Reprod Endocrinol 4:131–141

    Article  Google Scholar 

  51. Wendelin DS, Pope DN, Mallory SB (2003) Hypertrichosis. J Am Acad Dermatol 48:161–179

    Article  PubMed  Google Scholar 

  52. Al-Nuaimi Y, Baier G, Watson REB et al (2010) The cycling hair follicle as an ideal systems biology research model. Exp Dermatol 19:707–713

    Article  PubMed  PubMed Central  Google Scholar 

  53. Burger HG (2002) Androgen production in women. Fertil Steril 77:S3–S5

    Article  PubMed  Google Scholar 

  54. Alonso L, Fuchs E (2006) The hair cycle. J Cell Sci 119(Pt3):391–393

    Article  CAS  PubMed  Google Scholar 

  55. Escobar-Morreale HF, Carmina E, Dewailly D et al (2012) Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society. Hum Reprod Update 18:146–170

    Article  CAS  PubMed  Google Scholar 

  56. Zouboulis CC (2004) Acne and sebaceous gland function. Clin Dermatol 22:360–366

    Article  PubMed  Google Scholar 

  57. Zouboulis CC, Degitz K (2004) Androgen action on human skin—from basic research to clinical significance. Exp Dermatol 13(supplement 4):5–10

    Article  CAS  PubMed  Google Scholar 

  58. Makrantonaki E, Ganceviciene R, Zouboulis C (2011) An update on the role of the sebaceous gland in the pathogenesis of acne. Derm Endocrinol 3:41–49

    Article  Google Scholar 

  59. Cela E, Robertson C, Rush K et al (2003) Prevalence of polycystic ovaries in women with androgenic alopecia. Eur J Endocrinol 149:439–442

    Article  CAS  PubMed  Google Scholar 

  60. Price VH (2003) Androgenetic alopecia in women. J Invest Dermatol Symp Proc 8:24–27

    Article  Google Scholar 

  61. Daniel CR III, Iorizzo M, Piraccini BM, Tosti A (2011) Simple onycholysis. Cutis 87:226–228

    PubMed  Google Scholar 

  62. Van de Kerkhof PCM, Paschc MC, Scher RK et al (2005) Brittle nail syndrome: a pathogenesis-based approach with a proposed grading system. J Am Acad Dermatol 53:644–651

    Article  PubMed  Google Scholar 

  63. Femiano F, Rullo R, Serpico R et al (2009) An unusual case of oral hirsutism in a patient with polycystic ovarian syndrome. Oral Med Oral Pathol Oral Radiol Endod 108:e13–e16

    Article  Google Scholar 

  64. Canaris GJ, Manowitz NR, Mayor G et al (2000) The Colorado thyroid disease prevalence study. Arch Intern Med 160:526–534

    Article  CAS  PubMed  Google Scholar 

  65. Dayan CM, Daniels GH (1996) Chronic autoimmune thyroiditis. N Engl J Med 335:99–107

    Article  CAS  PubMed  Google Scholar 

  66. Cooper DS (2001) Subclinical hypothyroidism. N Engl J Med 345:260–265

    Article  CAS  PubMed  Google Scholar 

  67. Petrikova J, Lazurova I, Yehuda S (2010) Polycystic ovary syndrome and autoimmunity. Eur J Intern Med 21:369–371

    Article  PubMed  Google Scholar 

  68. Benetti-Pinto CL, Santana Berini Piccolo VR, Garmes HM et al (2013) Subclinical hypothyroidism in young women with polycystic ovary syndrome: an analysis of clinical, hormonal, and metabolic parameters. Fertil Steril 99(2):588–592

    Article  CAS  PubMed  Google Scholar 

  69. Mueller A, Schofl C, Dittrich R et al (2009) Thyroid stimulating hormone is associated with insulin resistance independently of body mass index and age in women with polycystic ovary syndrome. Hum Reprod 24:2924–2930

    Article  CAS  PubMed  Google Scholar 

  70. Kelley DE, Mandarino LJ (1988) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–683

    Article  Google Scholar 

  71. Kelley DE, Goodpaster B, Wing RR, Simoneau JA (1999) Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity and weight loss. Am J Physiol 277:E1130–E1141

    CAS  PubMed  Google Scholar 

  72. Ukropcova B, Sereda O, de Jonge L et al (2007) Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes 56:720–727

    Article  CAS  PubMed  Google Scholar 

  73. Diamanti-Kandaris E, Dunaif A (2012) Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 33:981–1030

    Article  CAS  Google Scholar 

  74. Glueck CJ, Papanna R, Wang P et al (2003) Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 52:908–915

    Article  CAS  PubMed  Google Scholar 

  75. Ehrmann DA et al (2006) Prevalence and predictors of metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 91:48–53

    Article  CAS  PubMed  Google Scholar 

  76. Apridonidze et al (2005) Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:1929–1935

    Article  CAS  PubMed  Google Scholar 

  77. Ford ES et al (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359

    Article  PubMed  Google Scholar 

  78. Hoffman LK, Ehrmann DA (2008) Cardiometabolic features of polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab 4(4):215–222

    Article  CAS  PubMed  Google Scholar 

  79. Coviello AD, Legro RS, Dunaif A (2006) Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab 91:492–497

    Article  CAS  PubMed  Google Scholar 

  80. Leibel NI, Baumann E, Kocherginsky M, Rosenfield R (2006) Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome. J Clin Endocrinol Metab 91:1275–1283

    Article  CAS  PubMed  Google Scholar 

  81. Haffner S, Taegtmeyer H (2003) Epidemic obesity and metabolic syndrome. Circulation 108(13):1541–1545

    Google Scholar 

  82. Dunaif A, Finegood DT (2006) Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 81:942–947

    Google Scholar 

  83. Ehrmann DA, Sturis J, Byrne MM et al (1995) Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 96:520–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mahabeer S, Jialal I, Norman RJ et al (1989) Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease. Horm Metab Res 21:502–506

    Article  CAS  PubMed  Google Scholar 

  85. O’Meara NM, Blackman JD, Ehrmann DA et al (1993) Defects in beta-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 76:1241–1247

    PubMed  Google Scholar 

  86. Cara JF et al (1998) Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology 123:733–739

    Article  Google Scholar 

  87. Dunaif A et al (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38:1165–1174

    Article  CAS  PubMed  Google Scholar 

  88. Lambrinoudaki I (2010) Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome. Maturitas 68(1):13–16

    Article  PubMed  Google Scholar 

  89. Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 22:1145–1158

    Article  CAS  PubMed  Google Scholar 

  90. Spiegelman BM, Flier JS (1996) Adipogenesis and obesity: rounding out the big picture. Cell 87:377–389

    Article  CAS  PubMed  Google Scholar 

  91. Fruhbeck G (2004) The adipose tissue as a source of vasoactive factors. Curr Med Chem Cardiovasc Hematol Agents 2:197–208

    Article  CAS  PubMed  Google Scholar 

  92. Lee YH, Pratley RE (2005) The evolving role of inflammation in obesity and metabolic syndrome. Curr Diab Rep 5(1):70–75

    Article  CAS  PubMed  Google Scholar 

  93. Hausman DB, DiGirolamo M, Bartness TJ et al (2001) The biology of white adipocyte proliferation. Obes Rev 2(4):239–254

    Article  CAS  PubMed  Google Scholar 

  94. Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  CAS  PubMed  Google Scholar 

  96. Rondinone CM (2006) Adipocyte-derived hormones, cytokines, and mediators. Endocrine 29:81–90

    Article  CAS  PubMed  Google Scholar 

  97. Yu YH, Ginsberg HN (2005) Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ Res 96:1042–1052

    Article  CAS  PubMed  Google Scholar 

  98. Halleux CM, Takahashi M, Delporte ML et al (2001) Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 288:1102–1107

    Article  CAS  PubMed  Google Scholar 

  99. Matsubara M, Maruoka S, Katayose S (2002) Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 87:2764–2769

    Article  CAS  PubMed  Google Scholar 

  100. Yang WS, Lee WJ, Funahashi T, Tanaka S et al (2001) Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819

    Article  CAS  PubMed  Google Scholar 

  101. Kazumi T, Kawaguchi A, Yoshino G et al (2002) Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 25:971–976

    Article  PubMed  Google Scholar 

  102. Weyer C, Funahashi T, Tanaka S et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935

    Article  CAS  PubMed  Google Scholar 

  103. Stefan N, Bunt JC, Salbe AD et al (2002) Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab 87:4652–4656

    Article  CAS  PubMed  Google Scholar 

  104. Arita Y, Kihara S, Ouchi N et al (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83

    Article  CAS  PubMed  Google Scholar 

  105. Hotta K, Funahashi T, Arita Y et al (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599

    Article  CAS  PubMed  Google Scholar 

  106. Spranger J, Kroke A et al (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228

    Article  CAS  PubMed  Google Scholar 

  107. Toulis KA, Goulis DG et al (2009) Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update 15:297–307

    Article  CAS  PubMed  Google Scholar 

  108. Barber TM, Franks S (2013) Adipocyte biology in polycystic ovary syndrome. Mol Cell Endocrinol 373:68–76

    Article  CAS  PubMed  Google Scholar 

  109. Fruhbeck G, Gomez-Ambrosi J (2001) Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide. Cell Signal 13:827–833

    Article  CAS  PubMed  Google Scholar 

  110. Maffei M, Halaas J, Ravussin E et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and obRNA in obese and weight-reduced subjects. Nat Med 1:1155–1161

    Article  CAS  PubMed  Google Scholar 

  111. Calvar CE, Intebi AD, Bengolea SV et al (2003) Leptin in patients with polycystic ovary syndrome. Direct correlation with insulin resistance. Medicina (B Aires) 63:704–710

    CAS  Google Scholar 

  112. Zachow RJ, Magoffin DA (1997) Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent estradiol-17 beta production by rat ovarian granulosa cells. Endocrinology 138:847–850

    CAS  PubMed  Google Scholar 

  113. Wang P, Vanhoutte PM, Miao CY (2011) Visfatin and cardio-cerebro-vascular disease. J Cardiovasc Pharmacol 59:1–9

    Article  CAS  Google Scholar 

  114. Yildiz BO, Bozdag G, Otegen U et al (2010) Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant women with PCOS. Reprod Biomed Online 20:150–155

    Article  CAS  PubMed  Google Scholar 

  115. Cekmez F, Cekmez Y, Pirgon O et al (2011) Evaluation of new adipocytokines and insulin resistance in adolescents with polycystic ovary syndrome. Eur Cytokine Netw 22:32–37

    CAS  PubMed  Google Scholar 

  116. Dikmen E, Tarkun I, Canturk Z, Cetinarslan B (2010) Plasma visfatin level in women with polycystic ovary syndrome. Gynecol Endocrinol 27:475–479

    Article  PubMed  CAS  Google Scholar 

  117. Manneras-Holm L, Leonhardt H, Kullberg J et al (2011) Adipose tissue has aberrant morphology and function in PCOS: enlarged adipocytes and low serum adiponectin, but not circulating sex steroids, are strongly associated with insulin resistance. J Clin Endocrinol Metab 96:E304–E311

    Article  CAS  PubMed  Google Scholar 

  118. Villa J, Pratley RE (2011) Adipose tissue dysfunction in polycystic ovary syndrome. Curr Diab Rep 11:179–184

    Article  CAS  PubMed  Google Scholar 

  119. Faulds G, Ryden M, Wahrenberg H, Arner P (2003) Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovary syndrome. J Clin Endocrinol Metab 88:2269–2273

    Article  CAS  PubMed  Google Scholar 

  120. Dicker A, Ryden M, Naslund E et al (2004) Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots. Diabetologia 47:420–428

    Article  CAS  PubMed  Google Scholar 

  121. Dunaif A, Segal KR, Shelley DR et al (1992) Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 41:1257–1266

    Article  CAS  PubMed  Google Scholar 

  122. Ciaraldi TP, Morales AJ, Hickman MG et al (1997) Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity. J Clin Endocrinol Metab 82:1421–1425

    CAS  PubMed  Google Scholar 

  123. Diamanti-Kandarakis E, Papavassiliou AG (2006) Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med 12:324–332

    Article  CAS  PubMed  Google Scholar 

  124. Danforth JE (2000) Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet 26(1):13

    Article  CAS  PubMed  Google Scholar 

  125. Barber TM, McCarthy MI, Wass JA, Franks S (2006) Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf) 65:137–145

    Article  CAS  Google Scholar 

  126. Giagulli VA, Verdonck L, Giorgino R, Vermeulen A (1989) Precursors of plasma androstanediol-and androgen-glucuronides in women. J Steroid Biochem 33:935–940

    Article  CAS  PubMed  Google Scholar 

  127. Stewart PM, Shackleton CH, Beastall GH, Edwards CR (1990) 5 alpha-reductase activity in polycystic ovary syndrome. Lancet 355:431–433

    Article  Google Scholar 

  128. Fassnacht M, Schlenz N, Schneider SB et al (2003) Beyond adrenal and ovarian androgen generation: increased peripheral 5alpha-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:2760–2766

    Article  CAS  PubMed  Google Scholar 

  129. Tsilchorozidou T, Honour JW, Conway GS (2003) Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates. J Clin Endocrinol Metab 88:5907–5913

    Article  CAS  PubMed  Google Scholar 

  130. Chin D, Shackleton C, Prasad VK et al (2000) Increased 5alpha-reductase and normal 11 beta-hydroxysteroid dehydrogenase metabolism of C19 and C21 steroids in a young population with polycystic ovarian syndrome. J Pediatr Endocrinol Metab 13:253–259

    Article  CAS  PubMed  Google Scholar 

  131. Engeli S, Schling P, Gorzelniak K et al (2003) The adipose tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome. Int J Biochem Cell Biol 35:807–825

    Article  CAS  PubMed  Google Scholar 

  132. Lee YH, Nair S, Rousseau E et al (2005) Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes. Diabetologia 48(9):1776–1783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Nonogaki K, Fuller GM, Fuentes NL et al (1995) Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136:2143–2149

    CAS  PubMed  Google Scholar 

  134. Kelly CC, Lyall H, Petrie JR et al (2001) Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 86:2453–2455

    Article  CAS  PubMed  Google Scholar 

  135. Bahceci M, Tuzcu A, Canoruc N et al (2004) Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance. Horm Res 62:283–287

    Article  CAS  PubMed  Google Scholar 

  136. Meden-Vrtovec H, Vrtovec B, Osredkar J (2007) Metabolic and cardiovascular changes in women with polycystic ovary syndrome. Int J Gynecol Obstet 99:87–90

    Article  CAS  Google Scholar 

  137. Cho LW, Randeva HS, Atkin SL (2007) Cardiometabolic aspects of polycystic ovarian syndrome. Vasc Health Risk Manag 3(1):55–63

    PubMed  PubMed Central  Google Scholar 

  138. Hahn S, Haselhorst U, Tan S et al (2006) Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 114:577–583

    Article  CAS  PubMed  Google Scholar 

  139. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  CAS  PubMed  Google Scholar 

  140. Pittas AG, Lau J, Hu FB, Dawson-Hughes B (2007) The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92:2017–2029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Freundlich M, Quiroz Y, Zhang Z et al (2008) Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. Kidney Int 74:1394–1402

    Article  CAS  PubMed  Google Scholar 

  142. Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79:820–825

    CAS  PubMed  Google Scholar 

  143. Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24:1496

    Article  CAS  PubMed  Google Scholar 

  144. Bikle D (2009) Nonclassic actions of vitamin D. J Clin Endocrinol Metabol 94:26–34

    Article  CAS  Google Scholar 

  145. Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132:2169–2180

    Article  CAS  PubMed  Google Scholar 

  146. Wehr E, Pilz S et al (2009) Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 161:575–582

    Article  CAS  PubMed  Google Scholar 

  147. Glintborg D, Andersen M, Hagen C, Hermann AP (2005) Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism. Clin Endocrinol (Oxf) 62:683–691

    Article  CAS  Google Scholar 

  148. Balen AH, Conway GS, Kaltsas G et al (1995) Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod 10:2107–2111

    Article  CAS  PubMed  Google Scholar 

  149. Carmina E, Koyama T, Chang L et al (1992) Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 167:1807–1812

    Article  CAS  PubMed  Google Scholar 

  150. Silfen ME, Denburg MR, Manibo AM et al (2003) Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J Clin Endocrinol Metab 88:4682–4688

    Article  CAS  PubMed  Google Scholar 

  151. Norman RJ, Wu R, Stankiewicz MT (2004) Polycystic ovary syndrome. Med J Aust 180:132–137

    PubMed  Google Scholar 

  152. Bjorntrop P (1997) Obesity. Lancet 350:423–426

    Article  Google Scholar 

  153. Basdevant A, Raison J, Guy-Grand B (1987) Influence of the distribution of the body fat on vascular risk. Presse Med 16:167–170

    CAS  PubMed  Google Scholar 

  154. Lefebvre P, Bringer J, Renard E et al (1997) Influence of weight, body fat patterning and nutrition on the management of PCOS. Hum Reprod 12(Suppl 1):72–81

    Article  PubMed  Google Scholar 

  155. Kirchengast S et al (2001) Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 16:1255–1260

    Article  CAS  PubMed  Google Scholar 

  156. Horejsi R et al (2004) Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women. Am J Phys Anthropol 124:275–281

    Article  CAS  PubMed  Google Scholar 

  157. Svendsen P, Nilas L, Norgaard K et al (2008) Obesity, body composition and metabolic disturbances in polycystic ovary syndrome. Hum Reprod 23:2113–2121

    Article  CAS  PubMed  Google Scholar 

  158. Williams DP, Boyden TW, Pamenter RW et al (1993) Relationship of body fat percentage and fat distribution with DHEA-S in premenopausal females. J Clin Endocrinol Metab 77:80–85

    CAS  PubMed  Google Scholar 

  159. Douchi T, Ijuin H, Nakamura S et al (1995) Body fat distribution in women with polycystic ovary syndrome. Obstet Gynecol 86:516–519

    Article  CAS  PubMed  Google Scholar 

  160. Arner P (2005) Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Metab 19:471–482

    Article  CAS  PubMed  Google Scholar 

  161. Nesto R (2004) C-reactive protein, its role in inflammation, type 2 diabetes and cardiovascular disease and the effects of insulin-sensitising treatment with thiazolidinediones. Diabetes Med 21:810–817

    Article  CAS  Google Scholar 

  162. Bays H, Mandarino L, DeFronzo RA (2004) Role of the adipocyte, free fatty acids and ectopic fat in the pathogenesis of type 2 diabetes mellitus: a peroxisome proliferators-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 89:463–478

    Article  CAS  PubMed  Google Scholar 

  163. Hsuch WA, Lyon CJ, Quinones MJ (2004) Insulin resistance and the endothelium. Am J Med 117:109–117

    Article  CAS  Google Scholar 

  164. Bhattacharya SM (2010) Insulin resistance and overweight-obese women with polycystic ovary syndrome. Gynecol Endocrinol 26(5):344–347

    Article  CAS  PubMed  Google Scholar 

  165. Masuzaki H, Flier JS (2003) Tissue-specific glucocorticoid reactivating enzyme, 11-beta-hydroxysteroid dehydrogenase type 1 – a promising drug target for the treatment of metabolic syndrome. Curr Drug Targets Immune Endocr Metab Disord 3:255–262

    Article  CAS  Google Scholar 

  166. Legro RS et al (1998) Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 95:14956–14960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Third report of the National Cholesterol education Program (NCEP) (2002) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421

    Google Scholar 

  168. Wild R (2012) Dyslipidemia in PCOS. Steroids 77:295–299

    Article  CAS  PubMed  Google Scholar 

  169. Pirwany IR, Fleming R et al (2001) Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters. Clin Endocrinol (Oxf) 54(4):447–453

    Article  CAS  Google Scholar 

  170. Pekala P, Kawakami M, Vine W et al (1983) Studies of insulin resistance in adipocytes induced by macrophage mediator. J Exp Med 157:1360–1365

    Article  CAS  PubMed  Google Scholar 

  171. Wild RA, Alaupovic P, Parker IJ (1992) Lipid and apolipoprotein abnormalities in hirsute women. I. The association with insulin resistance. Am J Obstet Gynecol 166(4):1191–1196

    Article  CAS  PubMed  Google Scholar 

  172. Ginsberg HN, Brown WV (2011) Apolipoprotein CIII: 42 years old and even more interesting. Arterioscler Thromb Vasc Biol 31(3):471–473

    Article  CAS  PubMed  Google Scholar 

  173. Dietschy JM, Brown MS (1974) Effect of alterations of the specific activity of the intracellular acetyl CoA pool on apparent rates of hepatic cholesterogenesis. J Lipid Res 15:508–516

    CAS  PubMed  Google Scholar 

  174. Cupisti S, Giltay EJ, Gooren LJ et al (2010) The impact of testosterone administration to female-to-male transsexuals on insulin resistance and lipid parameters compared with women with polycystic ovary syndrome. Fertil Steril 94:2647–2653

    Article  CAS  PubMed  Google Scholar 

  175. Fruzzetti F, Perini D, Lazzarini V et al (2009) Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels. Fertil Steril 92:626–634

    Article  CAS  PubMed  Google Scholar 

  176. Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA et al (2007) Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 18:280–285

    Article  CAS  PubMed  Google Scholar 

  177. Legro RS (2001) Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 111:607–613

    Article  CAS  PubMed  Google Scholar 

  178. Conway GS, Agrawal R, Betteridge DJ et al (1992) Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf) 37:119–125

    Article  CAS  Google Scholar 

  179. Holte J, Bergh T, Berne C et al (1994) Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables. Clin Endocrinol (Oxf) 41:463–471

    Article  CAS  Google Scholar 

  180. Legro RS, Blanche P, Krauss RM et al (1999) Alterations in low-density lipoprotein and high-density lipoprotein subclasses among Hispanic women with polycystic ovary syndrome: influence of insulin and genetic factors. Fertil Steril 72:990–995

    Article  CAS  PubMed  Google Scholar 

  181. Robinson S, Henderson AD, Gelding SV et al (1996) Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries. Clin Endocrinol (Oxf) 44:277–284

    Article  CAS  Google Scholar 

  182. Wild RA, Painter PC, Coulson PB et al (1985) Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 61:946–951

    Article  CAS  PubMed  Google Scholar 

  183. Rocha MP, Marcondes JAM, Barcellos CRG et al (2011) Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors. Gynecol Endocrinol 27(10):814–819

    Article  CAS  PubMed  Google Scholar 

  184. Wilson PW, Abbott RD, Castelli WP (1988) High density lipoprotein cholesterol and mortality. The Framingham heart study. Arteriosclerosis 8:737–741

    Article  CAS  PubMed  Google Scholar 

  185. Vrbikova J, Zamrazilova H, Sedlackova B, Snajderova M (2011) Metabolic syndrome in adolescents with polycystic ovary syndrome. Gynecol Endocrinol 27(10):820–822

    Article  CAS  PubMed  Google Scholar 

  186. Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332:1519–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Ciotta L, Pagano I, Stracquadanio M, Formuso C (2011) Incidenza di sindrome dell’ovaio policistico in giovani donne affette da steatosi epatica non alcolica. Minerva Ginecol 63:429–437

    CAS  PubMed  Google Scholar 

  188. Ahima RS (2007) Insulin resistance: cause or consequence of nonalcoholic steatohepatitis? Gastroenterology 132:444–446

    Article  CAS  PubMed  Google Scholar 

  189. Clark JM, Brancati FL, Diehl AM (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 98:960–967

    Article  CAS  PubMed  Google Scholar 

  190. Cortez-Pinto H, de Moura MC, Day CP (2006) Non-alcoholic steatohepatitis: from cell biology to clinical practice. J Hepatol 44:197–208

    Article  CAS  PubMed  Google Scholar 

  191. Schwimmer JB, Khorram O, Chiu V, Schwimmer WB (2005) Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 83:494–497

    Article  CAS  PubMed  Google Scholar 

  192. Setji TL, Holland ND, Sanders LL et al (2006) Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 91:1741–1747

    Article  CAS  PubMed  Google Scholar 

  193. Lavine JE, Schwimmer JB (2004) Nonalcoholic fatty liver disease in the pediatric population. Clin Liver Dis 8:549

    Article  PubMed  Google Scholar 

  194. Cerda C, Perez-Ayuso RM et al (2007) Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. J Hepatol 47:412–417

    Article  CAS  PubMed  Google Scholar 

  195. Gambarin-Gelwan M, Kinkhabwala SV, Schiano TD et al (2007) Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Clin Gastroenterol Hepatol 5:496–501

    Article  PubMed  Google Scholar 

  196. Baranova A, Tran TP, Birerdinc A, Younossi ZM (2011) Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 33:801–814

    Article  CAS  PubMed  Google Scholar 

  197. Jones H, Sprung V, Pugh CJA et al (2012) Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab 97(10):3709–3716

    Article  CAS  PubMed  Google Scholar 

  198. Brzozowska MM, Ostapowicz G, Weltman MD (2009) An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome. J Gastroenterol Hepatol 24:243–247

    Article  CAS  PubMed  Google Scholar 

  199. Barfield E, Liu YH, Kessler M et al (2009) The prevalence of abnormal liver enzymes and metabolic syndrome in obese adolescent females with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 22:318–322

    Article  PubMed  Google Scholar 

  200. Cascella T, Palomba S et al (2006) Serum aldosterone concentration and cardiovascular risk in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 91:4395–4400

    Article  CAS  PubMed  Google Scholar 

  201. Zavaroni I, Coruzzi P, Bonini L et al (1995) Association between salt sensitivity and insulin concentrations in patients with hypertension. Am J Hypertens 8:855–858

    Article  CAS  PubMed  Google Scholar 

  202. Resnick LM (1992) Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. Am J Med 93:11S–20S

    Article  CAS  PubMed  Google Scholar 

  203. Muller-Wieland D, Kotzka J, Knebel et al (1998) Metabolic syndrome and hypertension: pathophysiology and molecular basis of insulin resistance. Basic Res Cardiol 93(Suppl 2):131–134

    Article  PubMed  Google Scholar 

  204. Sechi LA, Bartoli E (1996) Molecular mechanisms of insulin resistance in arterial hypertension. Blood Press Suppl 1:47–54

    CAS  PubMed  Google Scholar 

  205. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities – the role of insulin resistance and the sympathoadrenal system. N Engl J Med 334:374–381

    Article  CAS  PubMed  Google Scholar 

  206. Barcellos CRG, Rocha MP, Hayashida SAY et al (2007) Impact of body mass index on blood pressure levels in patients with polycystic ovary syndrome. Arq Bras Endocrinol Metab 51(7):1104–1109

    Article  Google Scholar 

  207. Orio F Jr et al (2004) The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study. J Clin Endocrinol Metab 89:3696–3701

    Article  CAS  PubMed  Google Scholar 

  208. Yarali H et al (2001) Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome. Fertil Steril 76:511–516

    Article  CAS  PubMed  Google Scholar 

  209. Dahlgren E et al (1992) Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 57:507–513

    Google Scholar 

  210. Zimmerman S et al (1992) Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance. J Clin Endocrinol Metab 75:508–513

    Google Scholar 

  211. Dahlgren E et al (1992) Polycystic ovary syndrome and risk of myocardial infarction: evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 71:599–604

    Article  CAS  PubMed  Google Scholar 

  212. Holte J et al (1996) Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: a sign of pre-hypertensive state? Hum Reprod 11:23–28

    Article  CAS  PubMed  Google Scholar 

  213. Elting MW, Korsen TJM, Bezemer PD et al (2001) Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum Reprod 16:556–660

    Article  CAS  PubMed  Google Scholar 

  214. Cibula D, Cifkova R, Fanta M et al (2000) Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 15:785–789

    Article  CAS  PubMed  Google Scholar 

  215. Vrbikova J, Cifkova R et al (2003) Cardiovascular risk factors in young Czech females with polycystic ovary syndrome. Hum Reprod 18:980–984

    Article  CAS  PubMed  Google Scholar 

  216. Pauli JM, Raja-Khan N, Wu X, Legro RS (2011) Current perspectives of insulin resistance and polycystic ovary syndrome. Diabet Med 28(12):1445–1454

    Article  CAS  PubMed  Google Scholar 

  217. Ehrmann DA, Barnes RB, Rosenfield RL et al (1999) Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22:141–146

    Article  CAS  PubMed  Google Scholar 

  218. Celik C, Tasdemir N, Abali R et al (2014) Progression to impaired glucose tolerance or type 2 diabetes mellitus in polycystic ovary syndrome: a controlled follow-up study. Fertil Steril 101:1123–1128

    Article  CAS  PubMed  Google Scholar 

  219. Kim JJ, Choi YM, Cho YM et al (2012) Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome. Hum Reprod 27:1439–1444

    Article  CAS  PubMed  Google Scholar 

  220. Barrett-Connor E, Giardina EG, Gitt AK et al (2004) Women and heart disease: the role of diabetes and hyperglycemia. Arch Intern Med 164(9):934–942

    Article  PubMed  Google Scholar 

  221. Wild S, Pierpoint T, McKeigue P, Jacobs H (2000) Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 52:595–600

    Article  CAS  Google Scholar 

  222. Bierwolf C, Struve K, Marshall L et al (1997) Slow wave sleep drives inhibition of pituitary-adrenal secretion in humans. J Neuroendocrinol 9:479–484

    Article  CAS  PubMed  Google Scholar 

  223. Ip MS, Lam B, Ng MM et al (2002) Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165:670–676

    Article  PubMed  Google Scholar 

  224. Punjabi NM, Sorkin JD, Katzel LI et al (2002) Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 165:677–682

    Article  PubMed  Google Scholar 

  225. Meslier N, Gagnadoux F, Giraud P et al (2003) Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Respir J 22:156–160

    Article  CAS  PubMed  Google Scholar 

  226. Punjabi NM, Shahar E, Redline S et al (2004) Sleep-disordered breathing, glucose intolerance, and insulin resistance: the sleep heart health study. Am J Epidemiol 160:521–530

    Article  PubMed  Google Scholar 

  227. Tassone F, Lanfranco F, Gianotti L et al (2003) Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables. Clin Endocrinol (Oxf) 59:374–379

    Article  Google Scholar 

  228. Rexrode KM et al (2003) Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation 108:1688–1693

    Article  CAS  PubMed  Google Scholar 

  229. Vgontzas AN et al (2001) Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 86:517–520

    CAS  PubMed  Google Scholar 

  230. Fogel RB et al (2001) Increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. J Clin Endocrinol Metab 86:1175–1180

    CAS  PubMed  Google Scholar 

  231. Gopal M et al (2002) The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med 3:401–404

    Article  PubMed  Google Scholar 

  232. Mokhlesi B, Scoccia B, Mazzone T, Sam S (2012) Risk of obstructive sleep apnea in obese and non-obese women with polycystic ovary syndrome and healthy reproductively normal women. Fertil Steril 97(3):786–791

    Article  PubMed  PubMed Central  Google Scholar 

  233. Tasali E, Van Cauter E, Ehrmann DA (2006) Relationships between sleep disordered breathing and glucose metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab 91:36–42

    Article  CAS  PubMed  Google Scholar 

  234. Tasali E, Van Cauter E, Hoffman L, Ehrmann DA (2008) Impact of obstructive sleep apnea on insulin resistance and glucose tolerance in women with polycystic ovary syndrome. J Clin Endocrinol Metab 93:3878–3884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Driver HS, McLean H, Kumar DV et al (2005) The influence of the menstrual cycle on upper airway resistance and breathing during sleep. Sleep 28:449–456

    PubMed  Google Scholar 

  236. Pien GW, Schwab RJ (2004) Sleep disorders during pregnancy. Sleep 27:1405–1417

    PubMed  Google Scholar 

  237. Popovic RM, White DP (1998) Upper airway muscle activity in normal women: influence of hormonal status. J Appl Physiol 84:1055–1062

    CAS  PubMed  Google Scholar 

  238. Randeva H, Tan BK et al (2012) Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev 33(5):812–841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Bauer K (1993) Laboratory markers of coagulation activation. Arch Pathol Lab Med 117:71–77

    CAS  PubMed  Google Scholar 

  240. Lowe GDO (1987) Blood rheology in general medicine and surgery. Baillieres Clin Haematol 1:827–862

    Article  CAS  PubMed  Google Scholar 

  241. Mchedlishvili G (1998) Disturbed blood flow structuring as critical factor of hemorheological disorders in microcirculation. Clin Hemorheol Microcirc 19:315–325

    CAS  PubMed  Google Scholar 

  242. Patterson W, Caldwell C, Doll D (1990) Hyperviscosity syndromes and coagulopathies. Semin Oncol 17:210–216

    CAS  PubMed  Google Scholar 

  243. Koenig W, Sund M et al (1998) Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992. Arterioscler Thromb Vasc Biol 18:768–772

    Article  CAS  PubMed  Google Scholar 

  244. Koenig W, Sund M et al (2000) Association between plasma viscosity and all-cause mortality: results from the MONICA-Augsburg Cohort Study 1984–92. Br J Haematol 109:453–458

    Article  CAS  PubMed  Google Scholar 

  245. Coata G, Ventura F, Lombardini R et al (1995) Effect of low-dose oral triphasic contraceptives on blood viscosity, coagulation and lipid metabolism. Contraception 52:151–157

    Article  CAS  PubMed  Google Scholar 

  246. Erdem NT, Ercan M et al (2003) Plasma viscosity as an early cardiovascular risk factor in hirsute women with eumenorrhea or oligomenorrhea. Fertil Steril 80:1195–2008

    Article  PubMed  Google Scholar 

  247. Vervita V, Saltamavros AD, Adonakis G et al (2009) Obesity and insulin resistance increase plasma viscosity in young women with polycystic ovary syndrome. Gynecol Endocrinol 25(10):640–646

    Article  CAS  PubMed  Google Scholar 

  248. Caimi G, Sinagra D, Scarpitta AM, Lo Presti R (2001) Plasma viscosity and insulin resistance in metabolic syndrome. Int J Obestet 25:1856–1857

    Article  CAS  Google Scholar 

  249. Ercan M, Konukoglu D (2008) Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese female subjects. Clin Hemorheol Microcirc 38:227–234

    CAS  PubMed  Google Scholar 

  250. Sola E, Vaya A, Simo M et al (2007) Fibrinogen, plasma viscosity and blood viscosity in obesity. Relationship with insulin resistance. Clin Hemorheol Microcirc 37:309–318

    CAS  PubMed  Google Scholar 

  251. Dereli D, Ozgen G, Buyukkececi F et al (2003) Platelet dysfunction in lean women with polycystic ovary syndrome and association with insulin sensitivity. J Clin Endocrinol Metab 88:2263–2268

    Article  CAS  PubMed  Google Scholar 

  252. Trovati M, Mularoni EM, Burzacca S et al (1995) Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients. Diabetes 44:1318–1322

    Article  CAS  PubMed  Google Scholar 

  253. Ruggeri ZM (2002) Platelets in atherothrombosis. Nat Med 8:1227–1234

    Article  CAS  PubMed  Google Scholar 

  254. Gawaz M, Neumann FJ, Dickfeld T et al (1997) Vitronectin receptor (alpha(v)beta3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction. Circulation 96:1809–1818

    Article  CAS  PubMed  Google Scholar 

  255. Gawaz M, Brand K, Dickfeld T et al (2000) Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis. Atherosclerosis 148:75–85

    Article  CAS  PubMed  Google Scholar 

  256. Tateson JE, Moncada S, Jr V (1977) Effects of prostacyclin (Pgx) on cyclic AMP concentrations in human platelets. Prostaglandins 13:389–397

    Article  CAS  PubMed  Google Scholar 

  257. Shimokawa H (1999) Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol 31:23–37

    Article  CAS  PubMed  Google Scholar 

  258. Orio JRF, Palomba S, Cascella T et al (2004) Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. J Clin Endocrinol Metab 89:4588–4593

    Article  CAS  PubMed  Google Scholar 

  259. Kelly CJG, Speirs A, Gould GW et al (2002) Altered vascular function in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 87:742–746

    Article  CAS  PubMed  Google Scholar 

  260. Vincent D, Ilany J, Kondo T et al (2003) The role of endothelial insulin signalling in the regulation of vascular tone and insulin resistance. J Clin Invest 111:1372–1380

    Google Scholar 

  261. Vryonidou A, Papatheodorou A, Tavridou A et al (2005) Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:2740–2746

    Article  CAS  PubMed  Google Scholar 

  262. Paradisi G, Steinberg HO, Hempfling A et al (2001) Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 103:1410–1415

    Article  CAS  PubMed  Google Scholar 

  263. Bickerton AS, Clark N, Meeking D et al (2005) Cardiovascular risk in women with polycystic ovarian syndrome (PCOS). J Clin Pathol 58:151–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Kawashima S, Yokoyama M (2004) Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 24:998–1005

    Article  CAS  PubMed  Google Scholar 

  265. Bitar MS, Wahid S, Mustafa S et al (2005) Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes. Eur J Pharmacol 511:53–64

    Article  CAS  PubMed  Google Scholar 

  266. Bhagat K, Vallance P (1999) Effects of cytokines on nitric oxide pathways in human vasculature. Curr Opin Nephrol Hypertens 8:89–96

    Article  CAS  PubMed  Google Scholar 

  267. Chan WPA, Ngo DT, Sverdlov AL et al (2013) Premature aging of cardiovascular/platelet function in polycystic ovary syndrome. Am J Med 126:640.e1–640.e7

    Article  CAS  Google Scholar 

  268. Ouchi N, Ohishi M, Kihara S et al (2003) Association of hypoadiponectinemia with impaired vasoreactivity. Am J Med 42:231–234

    CAS  Google Scholar 

  269. Tan KC, Xu A, Chow WS et al (2004) Hypoadiponectinemia is associated with impaired vasoreactivity. J Clin Endocrinol Metab 89:765–769

    Article  CAS  PubMed  Google Scholar 

  270. Motoshima H, Wu X, Mahadev K, Goldstein BJ (2003) Adiponectin suppresses proliferation and superoxide generation and enhances NOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 315:264–271

    Article  CAS  Google Scholar 

  271. Fernandez-Real JM, Castro A, Vazquez G et al (2004) Adiponectin is associated with vascular function independent of insulin sensitivity. Diabetes Care 27:739–745

    Article  CAS  PubMed  Google Scholar 

  272. Matsuda M, Shimomura I, Sata M et al (2002) Role of adiponectin in preventing vascular stenosis: the missing link of adipovascular axis. Biol Chem 277:27487–37491

    Article  CAS  Google Scholar 

  273. Okamoto Y, Kihara S, Ouchi N et al (2002) Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106:2767–2770

    Article  CAS  PubMed  Google Scholar 

  274. Gonzalez F, Rote NS, Minium J, Kirwan JP (2006) Increased activation of nuclear factor kB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab 91:1508–1512

    Article  CAS  PubMed  Google Scholar 

  275. Piotrowski PC, Rzepczynska IJ et al (2005) Oxidative stress induces expression of CYP11A, CYP17, STAR and 3bHSD in rat theca-interstitial cells. J Soc Gynecol Investig 12(2 Suppl):319 A

    Google Scholar 

  276. Escobar-Morreale HF, Luque-Ramírez M, González F (2011) Serum inflammatory markers in polycystic ovary syndrome: a systematic review and meta-analysis. Fertil Steril 95:1048–1058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Blake G, Ridker P (2001) Novel clinical markers of vascular wall inflammation. Circ Res 89:763–771

    Article  CAS  PubMed  Google Scholar 

  278. Engin-Ustun Y, Ustun Y et al (2006) Are polycystic ovaries associated with cardiovascular disease risk as polycystic ovary syndrome. Gynecol Endocrinol 22(6):324–328

    Article  PubMed  Google Scholar 

  279. Yeh ET, Willerson JT (2003) Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation 107:370–371

    Article  PubMed  Google Scholar 

  280. Talbott EO et al (2004) The relationship between C-reactive protein and carotid intima-media thickness in middle-aged women with polycystic ovary syndrome. J Clin Endocrinol Metab 89:6061–6067

    Article  CAS  PubMed  Google Scholar 

  281. Talbottt EO et al (2004) Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab 89:5454–5461

    Article  CAS  Google Scholar 

  282. Christian RC et al (2003) Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:2562–2568

    Article  CAS  PubMed  Google Scholar 

  283. Shroff R et al (2007) Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab 92:4609–4614

    Article  CAS  PubMed  Google Scholar 

  284. Vanky E, Stridskelv S, Skogoy K et al (2011) PCOS – what matters in early pregnancy? Data from a cross-sectional, multicenter study. Acta Obstet Gynecol Scand 90:398–404

    Article  PubMed  Google Scholar 

  285. Freeman EW et al (2007) Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil Steril 87:101–106

    Article  CAS  PubMed  Google Scholar 

  286. Santoro N et al (2004) Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: the Study of Women’s Health across the Nation (SWAN) Daily Hormone Study. J Clin Endocrinol Metab 89:2622–2631

    Article  CAS  PubMed  Google Scholar 

  287. Robker RL et al (2009) Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J Clin Endocrinol Metab 94:1533–1540

    Article  CAS  PubMed  Google Scholar 

  288. Cardozo E, Pavone ME, Hirshfeld-Cytron JE (2011) Metabolic syndrome and oocyte quality. Trends Endocrinol Metab 22:103–109

    Article  CAS  PubMed  Google Scholar 

  289. Agarwal A et al (2005) Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 3:28

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  290. Marquard KL et al (2010) Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. doi:10.1016/j.fertnstert.2010.10.026

    PubMed Central  Google Scholar 

  291. Chakraborty P, Goswami SK, Rajani S et al (2013) Recurrent pregnancy loss in polycystic ovary syndrome: role of hyperhomocysteinemia and insulin resistance. PLoS One 8(e64446):1–6

    Google Scholar 

  292. Rai R, Clifford K, Regan L (1996) The modern preventative treatment of recurrent miscarriage. Br J Obstet Gynaecol 103:106–110

    Article  CAS  PubMed  Google Scholar 

  293. Rai R, Backos M, Rushworth F, Regan I (2000) Polycystic ovaries and recurrent miscarriage – a reappraisal. Hum Reprod 15:612–615

    Article  CAS  PubMed  Google Scholar 

  294. Amer SAK, Gopalan V, Li TC et al (2002) Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Hum Reprod 17:2035–2042

    Article  CAS  PubMed  Google Scholar 

  295. Ford HB, Schust DJ (2009) Recurrent pregnancy lost: etiology, diagnosis and therapy. Rev Obstet Gynecol 2:76–83

    PubMed  PubMed Central  Google Scholar 

  296. Jacubowics DJ, Iuorno MJ et al (2002) Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 87(2):524–529

    Article  Google Scholar 

  297. Jacobs HS, Homburg RR (1990) The endocrinology of conception. Baillieres Clin Endocrinol Metab 4:195–205

    Article  CAS  PubMed  Google Scholar 

  298. Van der Spuy ZM, Dyer SJ (2004) The pathogenesis of infertility and early pregnancy loss in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynecol 18:755–771

    Article  Google Scholar 

  299. Fenkci V, Fenkci S et al (2003) Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 80:123–127

    Article  PubMed  Google Scholar 

  300. Diamanti-Kandarakis E, Paterakis T et al (2006) Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 21:1426–1431

    Article  CAS  PubMed  Google Scholar 

  301. Vanky E, Salvesen KA, Asberg A, Carlsen SM (2008) Haemoglobin, C-reactive protein and androgen levels in uncomplicated and complicated pregnancies of women with polycystic ovary syndrome. Scand J Clin Lab Invest 68:421–426

    Article  CAS  PubMed  Google Scholar 

  302. Palomba S, Russo T, Falbo A et al (2012) Decidual endovascular trophoblast invasion in women with polycystic ovary syndrome: an experimental case-control study. J Clin Endocrinol Metab 97:2441–2449

    Google Scholar 

  303. Giudice LC (2006) Endometrium in PCOS: implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab 20:235–244

    Article  CAS  PubMed  Google Scholar 

  304. Tian L, Shen H, Lu Q et al (2007) Insulin resistance increases the risk of spontaneous abortion after assisted reproduction technology treatment. J Clin Endocrinol Metab 92:1430–1433

    Article  CAS  PubMed  Google Scholar 

  305. Maryam K, Bouzari Z, Basirat Z et al (2012) The comparison of insulin resistance frequency in patients with recurrent early pregnancy loss to normal individuals. BMC Res Notes 5:133. doi:10.1186/1756-0500-5-133

    Article  PubMed  PubMed Central  Google Scholar 

  306. Sun L, Lv H, Wei W et al (2010) Angiotensin-converting enzyme D/I and plasminogen activator inhibitor-1 4G/5G gene polymorphisms are associated with increased risk of spontaneous abortions in polycystic ovarian syndrome. J Endocrinol Invest 33:77–82

    Article  CAS  PubMed  Google Scholar 

  307. Gosman GG, Katcher HI, Legro RS (2006) Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 12:585–601

    Article  CAS  PubMed  Google Scholar 

  308. Atiomo WU, Bates SA, Condon JE et al (1998) The plasminogen activator inhibitor system in women with polycystic ovary syndrome. Fertil Steril 69:236–241

    Article  CAS  PubMed  Google Scholar 

  309. Schacter M, Raziel A, Friedler S et al (2003) Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod 18:721–727

    Article  CAS  Google Scholar 

  310. Wijeyaratne CN, Nirantharakumar K, Balen AH et al (2004) Plasma homocysteine in polycystic ovary syndrome: does it correlate with insulin resistance and ethnicity? Clin Endocrinol 60:560–567

    Article  CAS  Google Scholar 

  311. Boxmeer JC, Steegers-Theunissen R, Lindemans J et al (2008) Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation. Hum Reprod 23:2570–2576

    Article  CAS  PubMed  Google Scholar 

  312. Ebisch IM, Peters WH, Thomas CM et al (2006) Homocysteine, glutathione and related thiols affect fertility parameters in the (sub) fertile couple. Hum Reprod 21:1725–1733

    Article  CAS  PubMed  Google Scholar 

  313. Nafiye Y, Sevtap K, Muammer D et al (2010) The effect of serum and intrafollicular insulin resistance parameters and homocysteine levels of non-obese, nonhyperandrogenemic polycystic ovary syndrome patients on in vitro fertilization outcome. Fertil Steril 93:1864–1869

    Article  CAS  PubMed  Google Scholar 

  314. Motta AB (2012) The role of obesity in the development of polycystic ovary syndrome. Curr Pharm Des 18:2482–2491

    Article  CAS  PubMed  Google Scholar 

  315. Tulppala M, Stenman UH, Cacciatore B, Ylikorkala O (1993) Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women. Br J Obstet Gynaecol 100:348–352

    Article  CAS  PubMed  Google Scholar 

  316. Legro RS, Castracane VD, Kauffman RP (2004) Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 59:141–154

    Article  PubMed  Google Scholar 

  317. American College of Obstetricians and Gynecologists (ACOG) (2001) Gestational diabetes. ACOG Practice Bulletin, n. 30. Obstet Gynecol 98:525–538

    Article  Google Scholar 

  318. Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J (2003) Gestational diabetes and insulin resistance: role in short and long-term implications for mother and fetus. J Nutr 133:1674S–1683S

    CAS  PubMed  Google Scholar 

  319. Lo JC, Feigenbaum SL, Escobar GJ et al (2006) Increased prevalence of gestational diabetes mellitus among women with diagnosed polycystic ovary syndrome: a population-based study. Diabetes Care 29:1915–1917

    Article  PubMed  Google Scholar 

  320. Boomsma CM, Eijkemans MJCE, Hughes EG et al (2006) A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 12:673–683

    Article  CAS  PubMed  Google Scholar 

  321. Lanzone A, Fulghesu AM, Cucinelli F et al (1996) Preconceptional and gestational evaluation of insulin secretion in patients with polycystic ovary syndrome. Hum Reprod 11:2382–2386

    Article  CAS  PubMed  Google Scholar 

  322. Yogev Y, Langer O (2007) Spontaneous preterm delivery and gestational diabetes: the impact of glycemic control. Arch Gynecol Obstet 276:361–365

    Article  PubMed  Google Scholar 

  323. Palomba S, Falbo A, Russo T et al (2012) The risk of a persistent glucose metabolism impairment after gestational diabetes mellitus is increased in patients with polycystic ovary syndrome. Diabetes Care 35:861–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  324. Haakova L, Cibula D, Rezabek K et al (2003) Pregnancy outcome in women with PCOS and in controls matched by age and weight. Hum Reprod 18:1438–1441

    Article  CAS  PubMed  Google Scholar 

  325. Hu S, Leonard A, Seifalian A, Hardiman P (2007) Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod 22:1532–1539

    Article  PubMed  Google Scholar 

  326. Carlsen SM, Romundstad P, Jacobsen G (2004) Early second trimester hyperandrogenemia and subsequent preeclampsia: a prospective study. Acta Obstet Gynecol Scand 84:117–121

    Article  Google Scholar 

  327. Serin IS, Kula M, Basbug M et al (2001) Androgen levels of preeclamptic patients in the third trimester of pregnancy and six weeks after delivery. Acta Obstet Gynecol Scand 80:1009–1013

    Article  CAS  PubMed  Google Scholar 

  328. Steier JA, Ulstein M, Myking OL (2002) Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex. Obstet Gynecol 100:552–556

    CAS  PubMed  Google Scholar 

  329. Troisi R, Potischman N, Roberts JM et al (2003) Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies. Int J Epidemiol 32:455–460

    Article  PubMed  Google Scholar 

  330. Laivuori H, Kaaja R, Rutanen EM et al (1998) Evidence of high circulating testosterone in women with prior preeclampsia. J Clin Endocrinol Metab 83:344–347

    CAS  PubMed  Google Scholar 

  331. Hahnel ME, Martin JD, Michael CA, Hahnel R (1989) Metabolism of androstenedione by placental microsomes in pregnancy hypertension. Clin Chim Acta 181:103–108

    Article  CAS  PubMed  Google Scholar 

  332. Homburg R (2006) Pregnancy complications in PCOS. Best Pract Res Clin Endocrinol Metab 20:281–292

    Article  PubMed  Google Scholar 

  333. Boomsma CM, Fauser BC, Macklon NS (2008) Pregnancy complications in women with polycystic ovary syndrome. Semin Reprod Med 26(1):72–84

    Article  PubMed  Google Scholar 

  334. Pasquali R, Gambineri A (2006) Polycystic ovary syndrome: a multifaceted disease from adolescence to adult age. Ann N Y Acad Sci 1092:158–174

    Article  PubMed  Google Scholar 

  335. Rodriguez-Moran M, Guerrero-Romero F (2003) Insulin resistance is independently related to age in Mexican women. J Endocrinol Invest 26:42–48

    Article  CAS  PubMed  Google Scholar 

  336. Mansfield MJ, Emans SJ (1984) Adolescent menstrual irregularity. J Reprod Med 29:399–410

    CAS  PubMed  Google Scholar 

  337. Diamanti-Kandarakis E (2010) PCOS in adolescents. Best Pract Res Clin Obstet Gynaecol 24:173–183

    Article  PubMed  Google Scholar 

  338. Apter D, Vihko R (1985) Premenarcheal endocrine changes in relation to age at menarche. Clin Endocrinol (Oxf) 22:160–753

    Article  Google Scholar 

  339. Apter D (1980) Serum steroids and pituitary hormones in female puberty: a partly longitudinal study. Clin Endocrinol (Oxf) 12:107–120

    Article  CAS  Google Scholar 

  340. Hsu M-I (2013) Changes in the PCOS phenotype with age. Steroids 78:761–766

    Article  CAS  PubMed  Google Scholar 

  341. Wiksten-Almstromer M, Hirschberg AL, Hagenfeldt K (2008) Prospective follow-up of menstrual disorders in adolescence and prognostic factors. Acta Obstet Gynecol Scand 87:1162–1168

    Article  PubMed  Google Scholar 

  342. Holm K, Laursen EM, Brocks V, Muller J (1995) Pubertal maturation of the internal genitalia: an ultrasound evaluation of 166 healthy girls. Ultrasound Obstet Gynecol 6:175–181

    Article  CAS  PubMed  Google Scholar 

  343. Codner E, Villarroel C, Eyzaguirre FC et al (2011) Polycystic ovarian morphology in postmenarchal adolescents. Fertil Steril 95:702–706

    Article  PubMed  Google Scholar 

  344. Jeffrey CR, Coffler MS (2007) Polycystic ovary syndrome: early detection in the adolescent. Clin Obstet Gynecol 50:178–187

    Article  Google Scholar 

  345. Carmina E, Oberfield SE, Lobo RA (2010) The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol 203:201.e1–201.e5

    Article  Google Scholar 

  346. Ibanez L, Potau N, Virdis R et al (1993) Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab 76:1599–1603

    CAS  PubMed  Google Scholar 

  347. McCartney CR, Blank SK, Prendergast KA et al (2007) Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J Clin Endocrinol Metab 92:430–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  348. Lewy VD, Danadian K, Witchel SF, Arslanian S (2001) Early metabolic abnormalities in adolescent girls with polycystic ovary syndrome. J Pediatr 138:38–44

    Article  CAS  PubMed  Google Scholar 

  349. Carroll J, Saxena R, Welt CK (2012) Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome. J Pediatr Endocrinol Metab 25:459–466

    Article  PubMed  PubMed Central  Google Scholar 

  350. Rosenfield RL, Lipton RB, Drum ML (2009) Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatrics 123:84–88

    Article  PubMed  Google Scholar 

  351. Stark O, Peckham CS, Moynihan C (1989) Weight and age at menarche. Arch Dis Child 64:383–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  352. Welt CK, Carmina E (2013) Lifecycle of polycystic ovary syndrome (PCOS): from in utero to menopause. J Clin Endocrinol Metab 98(12):4629–4638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  353. Birdsall MA, Farquhar CM (1996) Polycystic ovaries in pre and post-menopausal women. Clin Endocrinol (Oxf) 44:269–276

    Article  CAS  Google Scholar 

  354. Elting MW, Korsen TJ, Rekers-Mombarg LT, Schoemaker J (2000) Women with polycystic ovary syndrome gain regular menstrual cycles when ageing. Hum Reprod 15:24–28

    Article  CAS  PubMed  Google Scholar 

  355. Elting MW, Kwee J, Korsen TJ et al (2003) Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles. Fertil Steril 79:1154–1160

    Article  PubMed  Google Scholar 

  356. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  357. Brown ZA, Louwers YV, Fong SL et al (2011) The phenotype of polycystic ovary syndrome ameliorates with aging. Fertil Steril 96:1259–1265

    Article  PubMed  Google Scholar 

  358. Davison SL, Bell R, Donath S et al (2005) Androgen levels in adult females: changes with age, menopause and oophorectomy. J Clin Endocrinol Metab 90:3847–3853

    Article  CAS  PubMed  Google Scholar 

  359. Carmina E, Campagna AM, Lobo RA (2012) A 20-year follow-up of young women with polycystic ovary syndrome. Obstet Gynecol 119:263–269

    Article  PubMed  Google Scholar 

  360. Winters SJ, Talbott E, Guzick DS et al (2000) Serum testosterone level decrease in middle age in women with polycystic ovary syndrome. Fertil Steril 73:724–729

    Article  CAS  PubMed  Google Scholar 

  361. Puurunen J, Piltonen T, Jaakola P et al (2009) Adrenal androgen production capacity remains high up to menopause in women with polycystic ovary syndrome. J Clin Endocrinol Metab 94:1973–1978

    Article  CAS  PubMed  Google Scholar 

  362. Puurunen J, Piltonen T, Morin-Papunen L et al (2011) Unfavorable hormonal, metabolic, and inflammatory alterations persist after menopause in women with PCOS. J Clin Endocrinol Metab 96(6):1827–1834

    Article  CAS  PubMed  Google Scholar 

  363. Alsamarai S, Adams JM, Murphy MK et al (2009) Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a function of age. J Clin Endocrinol Metab 94:4961–4970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  364. Tehrani FR, Solaymani-Dodaran M, Hedayati M, Azizi F (2010) Is polycystic ovary syndrome an exception for reproductive aging? Hum Reprod 25:1775–1781

    Article  CAS  PubMed  Google Scholar 

  365. La Marca A, Volpe A (2006) Anti-mullerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool? Clin Endocrinol (Oxf) 64:603–610

    Article  CAS  Google Scholar 

  366. Lambalk CB, van Disseldorp J, de Koning CH, Broekmans FJ (2009) Testing ovarian reserve to predict age at menopause. Maturitas 63:280–291

    Article  CAS  PubMed  Google Scholar 

  367. Rowe JW, Minaker KL, Pallotta JA, Flier SJ (1983) Characterization of the insulin resistance of aging. J Clin Invest 71:1581–1587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  368. Fink RI, Kolterman OG, Griffin J, Olefsky JM (1983) Mechanisms of insulin resistance in aging. J Clin Invest 71:1523–1535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  369. Schmidt J, Landin-Wilhelmsen K et al (2011) Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab 96:3794–3803

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Obstetrics and Gynecological Pathology, P.O. “S. Bambino”, University of Catania, Catania, Italy

    Mariagrazia Stracquadanio & Lilliana Ciotta

Authors
  1. Mariagrazia Stracquadanio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilliana Ciotta
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Stracquadanio, M., Ciotta, L. (2015). Clinical Features. In: Metabolic Aspects of PCOS. Springer, Cham. https://doi.org/10.1007/978-3-319-16760-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-16760-2_3

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-16759-6

  • Online ISBN: 978-3-319-16760-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation