Download PDF
Dtsch Med Wochenschr 2003; 128(43): 2261-2266
DOI: 10.1055/s-2003-43103
Übersichten
Endokrinologie
© Georg Thieme Verlag Stuttgart · New York

Polyzystisches Ovarsyndrom: Bedeutung der Insulinresistenz

Insulin resistence in polycystic ovary syndromeSt Grott1 , P. Algenstaedt1
  • 1Zentrum für Innere Medizin (Direktor: Prof. Dr. H. Greten), Universitätsklinikum Hamburg-Eppendorf
Further Information

Publication History

eingereicht: 18.7.2002

akzeptiert: 31.7.2003

Publication Date:
23 October 2003 (online)

Also available at
   Permissions and Reprints
Preview

Epidemiologie, Symptomatik und Definition

Das polyzystische Ovarsyndrom (PCOS) gehört mit einer Prävalenz von 5 - 10 % zu den häufigsten endokrinologischen Störungen der Frau [12]. Etwa drei Viertel aller Frauen mit Oligomenorrhoe und nahezu ein Drittel aller Frauen mit Amenorrhoe weisen die Diagnose PCOS auf [10] [18]. Das gemeinsame Auftreten von Amenorrhoe und Hirsutismus bei gleichzeitig bestehenden polyzystischen Ovarien wurde erstmals 1935 von Stein und Leventhal als eigenständiges Syndrom beschrieben [47]. Zu den möglichen Symptomen zählen:

Oligo-/Amenorrhoe, Anovulation mit Infertilität, Hyperandrogenämie mit Hirsutismus, Akne und Alopezie, Insulinresistenz und Adipositas, Dyslipoproteinämie.

Eine einheitliche Definition des polyzystischen Ovarsyndroms existiert bisher nicht. US-amerikanische Minimalkriterien sind das Vorliegen einer Oligo-/Amenorrhoe sowie klinische oder biochemische Hinweise einer Hyperandrogenämie unter Ausschluss anderer Ursachen einer Hyperandrogenämie [12]. Das sonomorphologische Bild der polyzystischen Ovarien ist dort nicht notwendig, in Europa steht es jedoch neben typischer Klinik und Laborkonstellation mehr im Vordergrund der Diagnosestellung, eine eindeutige Übereinkunft wie in den USA gibt es hier bisher nicht [18].

Literatur

  • 1 Bates G, Whitworth M S. Effect of body weight reduction on plasma androgens in obese, infertile women.  Fertil Steril. 1992;  39 406-409
    Search in Google Scholar
  • 2 Beckman J A, Creager M A, Libby P. Diabetes and atherosclerosis - epidemiology, pathophysiology, and management.  JAMA. 2002;  297 2570-2591
    Search in Google Scholar
  • 3 Book C B, Dunaif A. Selective Insulin Resistance in the Polycystic Ovary Syndrome.  J Clin Endocrinol Metab. 1999;  94 3110-3116
    Search in Google Scholar
  • 4 Burghen G A, Givens J R, Kitabchi A E. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease.  J Clin Endocrinol Metab. 1990;  50 113-116
    Search in Google Scholar
  • 5 Carey A H, Waterworth D, Patel K, White D, Little J, Novelli P, Franks S, Williamson R. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17.  Hum Mol Genet. 1994;  3 1973-1976
    Search in Google Scholar
  • 6 Cataldo N A, Abbasi F, McLaufhlin T L, Lamendola C, Reaven G M. Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone.  Fertil Steril. 2001;  76 1057-1059
    Search in Google Scholar
  • 7 Ciaraldi T P, El-Roeiy A, Madar Z, Reichart D, Olefsky J M, Yen S SC. Cellular Mechanisms of Insulin Resistance in Polycystic Ovarian Syndrome.  J Clin Endocrinol Metab. 1992;  75 577-593
    Search in Google Scholar
  • 8 Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Oden A, Janson P O, Mattson L, Crona N, Lundberg P. 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. 1992;  57 505-513
    Search in Google Scholar
  • 9 Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1996;  81 3299-3306
    Search in Google Scholar
  • 10 Dunaif A, Thomas A. Current Concepts in the Polycystic Ovary Syndrome.  Annu Rev Med. 2001;  52 401-419
    Search in Google Scholar
  • 11 Dunaif A, Xia J, Book C B, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and skeletal muscle: a potential mechanism for insulin resistance in the polycystic ovary syndrome.  J Clin Invest. 1995;  96 801-810
    Search in Google Scholar
  • 12 Dunaif A. Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis.  Endocrine Rev. 1997;  18 774-800
    Search in Google Scholar
  • 13 Ehrmann D A, Barnes R B, Rosenfield R L. Polyycystic Ovary Syndrome as a Form of Functional Ovarian Hyperandrogenism Due to Dysregulation of Androgen Secretion.  Endocrine Rev. 1995;  16 322-353
    Search in Google Scholar
  • 14 Ehrmann D A, Cavaghan M K, Barnes R B, Imperial J, Rosenfield R L. Prevalence of Impaired Glucose Tolerance and Diabetes in Women With Polycystic Ovary Syndrome.  Diabetes Care. 1999;  22 141-146
    Search in Google Scholar
  • 15 Ehrmann D A, Schneider D J, Sobel B E, Cavaghan M K, Imperial J, Rosenfield R L, Polonsky K S. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 2108-2116
    Search in Google Scholar
  • 16 Escobedo L G, Lee N C, Peterson H B, Wingo P A. Infertility-associated endometrial cancer risk may be limited to specific subgroups of infertile women.  Obstet Gynecol. 1991;  77 124-128
    Search in Google Scholar
  • 17 Franks S, Mason H, Willis D. Follicular dynamics in the polycystic ovary syndrome.  Mol Cell Endocrinol. 2000;  163 49-52
    Search in Google Scholar
  • 18 Franks S. Polycystic Ovary Syndrome.  N Engl J Med. 1995;  333 853-861
    Search in Google Scholar
  • 19 Fürnsinn C, Nowotny P, Brunmair B, Gras F, Roden M, Waldhäusl W, Vierhapper H. Thiazolidinediones Influence Plasma Steroids of Male Obese Zucker Rats.  Endocrinology. 2002;  143 327-330
    Search in Google Scholar
  • 20 Gharani N, Waterworth D M, Batty S, White D, Gilling-Smith C, Conway G s, McCarthy M, Franks S, Williamson R. Association of the steroid synthesis gene CYP11α with polycystic ovary syndrome and hyperandrogenism.  Hum Mol Genet. 1997;  6 397-402
    Search in Google Scholar
  • 21 Gharani N, Waterworth D M, Williamson R, Franks S. 5’Polymorphism of the CYP17 Gene is Not Associated with Serum Testosterone Levels in Women with Polycystic Ovaries.  J Clin Endocrinol Metab. 1996;  81 4174
    Search in Google Scholar
  • 22 Guzick D S, Wing R, Smith D, Berga S L, Winters S J. Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women.  Fertil Steril. 1994;  61 589-604
    Search in Google Scholar
  • 23 Holte J, Bergh T, Berne C, Wide L, Lithell H. Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1995;  80 2586-2593
    Search in Google Scholar
  • 24 Ito Y, Fisher C R, Conte F A, Grumbach M M, Simpson E R. Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.  Proc Natl Acad Sci USA. 1993;  90 11673-11677
    Search in Google Scholar
  • 25 Kelly C JG, Connell J MC, Cameron I T, Gould G W, Lyall H. The long term health consequences of polycystic ovary syndrome.  Br J Obstet Gynaecol. 2000;  107 1327-1338
    Search in Google Scholar
  • 26 Koivunen R, Laatikainen T, Tomas C, Huhtaniemi I, Tapanainen J, Martikainen H. Prevalence of polycystic ovary syndrome in healthy women.  Acta Obstet Gynecol Scand. 1999;  78 137-141
    Search in Google Scholar
  • 27 Krause J, Karasu T, Grunwald K, Neulen J. Syndrom der polyzystischen Ovarien: Klinische Einteilung.  Gynäkologe. 2002;  35 64-68
    Search in Google Scholar
  • 28 Legro R S, Kunselman A R, Dodson W C, 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;  84 165-169
    Search in Google Scholar
  • 29 Legro R S, Spielman R, Urbanek M. Phenotype and genotype in polycystic ovary syndrome.  Recent Prog Horm Res. 1998;  53 217-256
    Search in Google Scholar
  • 30 Lobo R A, Carmina E. The Importance of diagnosing the polycystic ovary syndrome.  Ann Intern Med. 2000;  132 989-993
    Search in Google Scholar
  • 31 Luft D, Schmulling R M, Eggstein M. Lactic acidosis in biguanide-treated diabetics: A review of 330 cases.  Diabetologia. 1978;  14 75-82
    Search in Google Scholar
  • 32 Matthaei S, Hamann A, Klein H H, Benecke H, Kreymann G, Flier J S, Greten H. Association of metformin effect to increase insulin-stimulated glucose transport with potentiation of insulin-induced translocation of glucose transporters from intracellular pool to plasma membrane in rat adipocytes.  Diabetes. 1993;  40 850-857
    Search in Google Scholar
  • 33 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and B cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
    Search in Google Scholar
  • 34 Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.  J Clin Endocrinol Metab. 2000;  85 139-146
    Search in Google Scholar
  • 35 Nestler J E, Jakubowicz D J, de Vargas A F, Brik C, Quintero N, Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system.  J Clin Endocrinol Metab. 1998;  83 2001-2005
    Search in Google Scholar
  • 36 Nestler J E, Jakubowicz D J, Evans W S, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.  N Engl J Med. 1998;  338 1876-1880
    Search in Google Scholar
  • 37 Nestler J E, Jakubowicz D J, Reamer P, Gunn R D, Allan G. Ovulatory and Metabolic Effects of D-Chiro-Inositol in the Polycystic Ovary Syndrome.  N Engl J Med. 1999;  340 1314-1320
    Search in Google Scholar
  • 38 Nestler J E, Powers L P, Matt D W, Steingold K A, Plymate S R, Rittmaster R S, Clore J N, Blackard W G. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1991;  72 83-89
    Search in Google Scholar
  • 39 Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, Fiorini S, Cognigni G E, Filicori M, Morselli-Labate A M. 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 2767-2774
    Search in Google Scholar
  • 40 Pierpoint T, McKeigue P M, Isaacs A J, Wild S H, Jacobs H S. Mortality of women with polycystic ovary syndrom at long-term follow-up.  J Clin Epidemiol. 1998;  51 581-586
    Search in Google Scholar
  • 41 Reaven G M, Litthell H, Landsberg L. Hypertension and associated metabolic abnormalities - the role of insulin resistance and the sympathoadrenal system.  N Engl J Med. 1996;  334 374-381
    Search in Google Scholar
  • 42 Romualdi D, Guido M, Ciampelli M, Giuliani M, Leoni F, Perri C, Lanzone A. Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome.  Hum Reprod. 2003;  18 1210-1218
    Search in Google Scholar
  • 43 Sampson M, Kong C, Patel A. et al . Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without polycystic ovary syndrome.  Clin Endocrinol (Oxf). 1996;  45 623-629
    Search in Google Scholar
  • 44 Singh A, Hamilton-Fairley D, Koistinen R, Seppala M, Janes V HT, Franks S, Reed M J. Effect of insulin-like growth factor-I (IGF-I) and insulin on the secretion of sex hormone-binding globulin and IGF-binding protein (IGFBP-1) by human hepatoma cels.  J Endocrinol. 1990;  124 R1-3
    Search in Google Scholar
  • 45 Slowey M J. Polycystic Ovary Syndrome: New Perspective on an Old Problem.  South Med J. 2001;  94 190-196
    Search in Google Scholar
  • 46 Spiegelman B M. PPAR-γ: Adipogenic Regulator and Thiazolidinedione Receptor.  Diabetes. 1998;  47 507-514
    Search in Google Scholar
  • 47 Stein I F, Leventhal M L. Amenorrhea associated with bilateral polycystic ovaries.  Am J Obstet Gynecol. 1935;  29 181-191
    Search in Google Scholar
  • 48 Takayama K, Fukaya T, Sasano H, Funayama Y, Suzuki T, Takaya R, Wada Y, Yajima A. Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome.  Hum Reprod. 1996;  11 1387-1392
    Search in Google Scholar
  • 49 Techatraisak K, Conway G S, Rumsby G. Frequency of a polymorphism in the regulatory region of the 17α-hydroxylase-17,20 lyase (CYP17) gene in hyperandrogenic states.  Clin Endocrinol. 1997;  46 131-134
    Search in Google Scholar
  • 50 Urbanek M, Legro R S, Driscoll D A, Azziz R, Ehrmann D A, Norman R J, Strauss J F, Spielman R S, Dunaif A. Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin.  Proc Natl Acad Sci USA. 1999;  96 8573-8578
    Search in Google Scholar
  • 51 Urbanek M, Wu X, Vickery K R, Kao L -C, Christenson L K, Schneyer A, Legro R S, Driscoll D A, Strauss I II JF, Dunaif A, Spielman R S. Allelic Variants of the Follistatin Gene in Polycystic Ovary Syndrome.  J Clin Endocrinol Metab. 2000;  85 4455-4461
    Search in Google Scholar
  • 52 Urman B, Sarac E, Dugan L, Gurgan T. Pregnancy in infertile PCOD patients: complications and outcome.  J Reprod Med. 1997;  442 501-505
    Search in Google Scholar
  • 53 Velazquez E M, Mendoza S G, Wang P, Glueck C J. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome.  Metabolism. 1997;  46 454-457
    Search in Google Scholar
  • 54 Willis D, Franks S. Insulin action in human granulosa cells from normal and poycystic ovaries is mediated by the insulin receptor and not the type-I insulin-like growth factor receptor.  J Clin Endocrinol Metab. 1995;  80 3788-3790
    Search in Google Scholar
  • 55 Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle stimulating and luteinizing hormone action in human granulosa cells of normal and polycystic ovaries.  J Clin Endocrinol Metab. 1996;  81 302-309
    Search in Google Scholar

Dr. med. Stefan Grott
c/o Dr. med. Petra Algenstaedt

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Innere Medizin

Martinistraße 52

20246 Hamburg

Email: algensta.uke.uni-hamburg.de