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Zentralbl Gynakol 2003; 125(12): 507-514
DOI: 10.1055/s-2003-44818
Originalarbeit

© Georg Thieme Verlag Stuttgart · New York

Der Einsatz oraler Antidiabetika in der Behandlung des Polyzystischen Ovarsyndroms

The Use of Oral Antidiabetic Drugs in the Treatment of Polycystic Ovary SyndromeS. Tauchert1 , A. K. Schröder1 , O. Ortmann2 , K. Diedrich1 , J. M. Weiss1
  • 1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig- Holstein, Campus Lübeck, Medizinische Universität zu Lübeck
  • 2Klinik für Frauenheilkunde und Geburtshilfe, Caritas-Krankenhaus St. Josef, Universität Regensburg
Further Information

Publication History

Publication Date:
15 December 2003 (online)

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Zusammenfassung

Das Polyzystische Ovarsyndrom (PCOS) ist die häufigste endokrine Erkrankung der Frau in der reproduktiven Lebensphase. Es ist ein komplexes Krankheitsbild mit metabolischen Störungen und ihren Langzeitfolgen. Als gesundheitliche Spätfolge droht die Entwicklung eines Diabetes mellitus Typ 2, der gemeinsam mit der häufig vorkommenden Adipositas und Dyslipidämie zu einem erhöhten Risiko kardiovaskulärer Erkrankungen führt. Die Insulinresistenz mit konsekutiver Hyperinsulinämie spielt eine Schlüsselrolle in der Pathophysiologie des PCOS.
Vor diesem Hintergrund erscheint eine Behandlung des PCOS durch orale Antidiabetika sinnvoll. Die Mehrzahl der Studien zeigte, dass diese Medikamente zu einer Verbesserung der typischen Symptome wie dem Hyperandrogenismus und der Zyklusunregelmäßigkeiten führten. Die Ovulations- und Schwangerschaftsraten wurden gesteigert. Darüber hinaus konnten kardioprotektive Wirkungen und eine verbesserte Insulinsensitivität, die möglicherweise auch beim PCOS vor der Entwicklung eines Diabetes mellitus Typ 2 schützt, nachgewiesen werden. Die vorliegende Übersicht beleuchtet den Einsatz verschiedener oraler Antidiabetika beim PCOS und ihren Einfluss auf die Fertilität, die drohende Entwicklung eines Diabetes mellitus und das Risiko kardiovaskulärer Erkrankungen.

Abstract

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a complex metabolic-endocrine disorder with severe long-term health consequences like type 2 diabetes. The increased risk for cardiovascular diseases in women with PCOS is due to diabetes, adipositas and dyslipidemia. Insulin resistance plays a key role in the pathophysiology of this syndrome.
This makes the use of oral antidiabetic drugs most compelling. The majority of studies have shown a melioration of the typical symptoms like hyperandrogenism and cycle irregularities. Ovulation and pregnancy rates increased. Furthermore these drugs might be cardioprotective by improving insulin sensitivity and reduce the risk for type 2 diabetes. This article reviews the use of different oral antidiabetic drugs in the treatment of PCOS and their influence on fertility, the risk for type 2 diabetes and cardiovascular diseases.

Schlüsselwörter

Polyzystische Ovarsyndrom (PCOS) - Hyperinsulinämie - orale Antidiabetika - Diabetes mellitus Typ 2

Key words

Polycystic ovary syndrome (PCOS) - hyperinsulinemia - oral antidiabetic drugs - type 2 diabetes

Literatur

  • 1 Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?.  Fertil Steril. 1996;  65 946-949
    PubMedGoogle Scholar
  • 2 Amowitz L L, Sobel B E. Cardiovascular consequences of polycystic ovary syndrome.  Endocrinol Metab Clin North Am. 1999;  28 439-458
    CrossrefPubMedGoogle Scholar
  • 3 Azziz R, Ehrmann D A, Legro R S, Whitcomb R W, Hanley R, Fereshetian A G, O'Keefe M, Ghazzi M N. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial.  J Clin Endocrinol Metab. 2001;  86 1626-1632
    CrossrefPubMedGoogle Scholar
  • 4 Azziz R, Ehrmann D A, Legro R S, Fereshetian A G, O'Keefe M, Ghazzi M N. Troglitazone decreases adrenal androgen levels in women with polycystic ovary syndrome.  Fertil Steril. 2003;  79 932-937
    CrossrefPubMedGoogle Scholar
  • 5 Bailey C J, Puah J A. Effect of metformin and glucose metabolism in mouse soleus muscle.  Diabet Metab. 1986;  12 212-218
    PubMedGoogle Scholar
  • 6 Bailey C J, Turner R C. Metformin.  N Engl J Med. 1996;  334 574-579
    CrossrefPubMedGoogle Scholar
  • 7 Barbieri R L, Smith S, Ryan K J. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism.  Fertil Steril. 1988;  50 197-212
    PubMedGoogle Scholar
  • 8 Barbieri R L. Metformin for the treatment of polycystic ovary syndrome.  Obstet Gynecol. 2003;  1001 785-793
    PubMedGoogle Scholar
  • 9 Bischoff H. The mechanism of alpha-glucosidase inhibition in the managment of diabetes.  Clin Invest Med. 1995;  18 303-311
    PubMedGoogle Scholar
  • 10 Buchanan T A, Xiang A H, Peters R K, Kjos S L, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz K, Hodis H N, Azen S P. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women.  Diabetes. 2002;  51 2796-2803
    CrossrefPubMedGoogle Scholar
  • 11 Cavaghan M, Ehrmann D, Byrne M, Polonsky K. Treatment with the oral antidiabetic agent troglitazone improves ß-cell responses to glucose in subjects with impaired glucose tolerance.  J Clin Invest. 1997;  100 530-537
    PubMedGoogle Scholar
  • 12 Ciaraldi T P, El Roeiy A, Madar Z, Reichhart D, Olefsky J M, Yen S S. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome.  J Clin Endocrinol Metab. 1992;  75 577-583
    PubMedGoogle Scholar
  • 13 Ciotta L, Calogero A E, Farina M, DeLeo V, La Marca A, Cianci A. Clinical, endocrine and metabolic effects of acarbose, an alpha-glucosidase inhibitor, in PCOS patients with increased insulin response and normal glucose tolerance.  Hum Reprod. 2001;  16 2066-2072
    CrossrefPubMedGoogle Scholar
  • 14 Coetzee E J, Jackson W P. Oral hypoglycaemics in the first trimester and fetal outcome.  Afr Med J. 1984;  65 635-637
    PubMedGoogle Scholar
  • 15 Conn J J, Jacobs H S, Conway G S. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus.  Clin Endocrinol. 2000;  52 81
    CrossrefPubMedGoogle Scholar
  • 16 Crave J C, Fimbel S, Lejeune H, Cugnardey N, Dechaud H, Pugeat M. Effects of diet and metformin administration on sex hormone binding globulin, androgens and insulin in hirsute and obese women.  J Clin Endocrinol Metab. 1995;  80 2057-2062
    CrossrefPubMedGoogle Scholar
  • 17 Dahlgren E, Janson P O, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarcation. Evaluated from a risk factor model based on a prospective population study of women.  Acta Obstet Gynecol Scand. 1992;  71 599-604
    CrossrefPubMedGoogle Scholar
  • 18 Dahlgren E, Janson P O, Johansson S, Lapidus L, Lindstedt G, Tengborn L. Hemostatic and metabolic variables in women with polycystic ovary syndrome.  Fertil Steril. 1994;  61 445-460
    PubMedGoogle Scholar
  • 19 DeLeo V, la Marca A, Ditto A, Morgante G, Cianci A. Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome.  Fertil Steril. 1999;  72 282-285
    CrossrefPubMedGoogle Scholar
  • 20 Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin in insulin resistance and hyperandrogenism in polycystic ovary syndrome.  Eur J Endocrinol. 1998;  138 269-274
    CrossrefPubMedGoogle Scholar
  • 21 Diamanti-Kandarakis E, Spina G, Kouli C, Migdalis I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy.  J Clin Endocrinol Metab. 2001;  86 4466-4473
    PubMedGoogle Scholar
  • 22 Dunaif A, Segal K R, Futterweit W, Dobransky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome.  Diabetes. 1989;  38 1165-1174
    CrossrefPubMedGoogle Scholar
  • 23 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.  Clin Endocrinol. 1995;  20 643-648
    PubMedGoogle Scholar
  • 24 Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabol and reproductive abnormalities in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1996;  81 3299-3306
    CrossrefPubMedGoogle Scholar
  • 25 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.  Endocr Rev. 1997;  18 774-780
    CrossrefPubMedGoogle Scholar
  • 26 Ehrmann D, Schneider D, Sobel B, Cavaghan M, Imperial J, Rosenfield R, Polonsky K. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidgenesis and fibrinolysis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 2108-2116
    CrossrefPubMedGoogle Scholar
  • 27 Ehrmann D A, Barnes R B, Rosenfield R L, Cavaghan M K, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.  Diabetes Care. 1999;  22 141-146
    CrossrefPubMedGoogle Scholar
  • 28 Ehrmann D A, Cavaghan M K, Imperial J, Sturis J, Rosenfield R L, Polonsky K S. Effects of metformin on insulin secretion, insulin action and ovarian steriodogenesis with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 524-530
    PubMedGoogle Scholar
  • 29 Fantus I G, Brosseau R. Mechanism of action of metformin: insulin receptor and postreceptor effects in vitro and in vivo.  J Clin Endocrinol Metab. 1986;  63 898-905
    PubMedGoogle Scholar
  • 30 Fleming R, Hopkinson Z E, Wallace A M, Greer I A, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.  J Clin Endocrinol Metab. 2002;  87 569-574
    CrossrefPubMedGoogle Scholar
  • 31 Franks S. Polycystic ovary syndrome.  N Engl J Med. 1995;  333 853-861
    CrossrefPubMedGoogle Scholar
  • 32 Geisthovel F, Frorath B, Brabant G. Acarbose reduces elevated testosterone serum concentration in hyperinsulinaemic premenopausal women: a pilot study.  Hum Reprod. 1996;  11 2377-2381
    CrossrefPubMedGoogle Scholar
  • 33 Ghazeeri G, Kutteh W H, Bryer-Ash M, Haas D, Ke R W. Effect of rosiglitazone on spontaneous and clomiphene citrat induced ovulation in women with polycystic ovary syndrome.  Fertil Steril. 2003;  79 562-566
    CrossrefPubMedGoogle Scholar
  • 34 Glueck C J, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91 %) previously amenorrhoic women with polycystic ovary syndrome.  Metabolism. 1999;  48 511-519
    CrossrefPubMedGoogle Scholar
  • 35 Hasegawa I, Murakawa H, Suzuki M, Yamamoto Y, Kurabayashi T, Tanaka K. Effect of troglitazone on endocrine and ovulatory performance in women with polycystic ovary syndrome.  Fertil Steril. 1999;  71 323-327
    CrossrefPubMedGoogle Scholar
  • 36 Hauner H. The mode of action of thiazolidinediones.  Diabetes Metab Res Rev. 2002;  18 10-15
    CrossrefPubMedGoogle Scholar
  • 37 Huber-Buchholz M M, Carey D G, Norman R J. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone.  J Clin Endocrinol Metab. 1999;  84 1470-1474
    CrossrefPubMedGoogle Scholar
  • 38 Ibanez L, Valls C, Ferrer A, Marcos M V, Rodriguez-Hierro F, de Zegher F. Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism.  J Clin Endocrinol Metab. 2001;  86 3595-3598
    CrossrefPubMedGoogle Scholar
  • 39 Inzucchi S E, Maggs D G, Spollett G R, Page S L, Rife F S, Walton V, Shulman G. Efficiency and metabolic effects of metformin and troglitazone in type II diabetes mellitus.  N Engl J Med. 1998;  338 867-872
    CrossrefPubMedGoogle Scholar
  • 40 Iuorno M J, Jakubowicz D J, Dillon P, Gunn R, Allan G, Nestler J E. Effects of d-chiro-inositol in the polycystic ovary syndrome.  Endocr Pract. 2002;  8 417-423
    CrossrefPubMedGoogle Scholar
  • 41 Johnson J A, Majumdar S R, Simpson S H, Toth E L. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes.  Diabetes Care. 2002;  25 2244-2248
    CrossrefPubMedGoogle Scholar
  • 42 Knochenhauer E S, Key T J, Kahsar-Miller M, Waggoner W, Boots L R, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospectve study.  J Clin Endocrinol Metab. 1998;  83 3078-3082
    CrossrefPubMedGoogle Scholar
  • 43 Knowler W C, Barrett-Connor E, Fowler S E, Hamman R F, Lachin J M, Walker E A, Nathan D M. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.  N Engl J Med. 2002;  346 393-403
    CrossrefPubMedGoogle Scholar
  • 44 Kocak M, Caliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates, cervical score and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 101-106
    PubMedGoogle Scholar
  • 45 Kolodziejczyk B, Duleba A J, Spaczynski R Z, Pawelczyk L. Metformin therapy improves hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.  Fertil Steril. 2000;  73 1149-1154
    Google Scholar
  • 46 Legro R S, Kunselman A R, Dodson W C, Dunaif A. Prevalence and predictors of risk for type 2 diabetes and impaired glucose tolerance in polycystic ovary syndrome: a prospective controlled study in 254 affected women.  J Clin Endocrinol Metab. 1999;  84 165-169
    CrossrefPubMedGoogle Scholar
  • 47 Legro R S, Kunselman A R, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome.  Am J Med. 2001;  111 607-613
    CrossrefPubMedGoogle Scholar
  • 48 Legro R S, Strauss J F. Molecular progress in infertility: polycystic ovary syndrome.  Fertil Steril. 2002;  78 569-576
    CrossrefPubMedGoogle Scholar
  • 49 Lord J M, Flight I CH, Norman R J. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.  Cochrane Databases Syst Rev. 2003;  3 CD003053
    PubMedGoogle Scholar
  • 50 Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  53 157-162
    CrossrefPubMedGoogle Scholar
  • 51 Mitwally M F, Kuscu N K, Yalcinkaya T M. High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome.  Hum Reprod. 1999;  14 2700-2703
    CrossrefPubMedGoogle Scholar
  • 52 Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolini 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 six-month trial followed by open, long-term clinical evaluation.  J Clin Endocrinol Metab. 2000;  85 139-146
    CrossrefPubMedGoogle Scholar
  • 53 Morin-Papunen L C, Koivunen R M, Roukonen A, Martikainen H K. Metformin therapy improves menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome.  Fertil Steril. 1998;  69 691-696
    CrossrefPubMedGoogle Scholar
  • 54 Morin-Papunen L C, Vauhkonen I, Koivunen R M, Ruokonen A, Martikainen H K, Tapanainen J S. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproteron acetate in obese women with polycystic ovary syndrome: a randomized study.  J Clin Endocrin Metab. 2000;  85 3161-3168
    PubMedGoogle Scholar
  • 55 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
    PubMedGoogle Scholar
  • 56 Ng E H, Wat N M, Ho P C. Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial.  Hum Reprod. 2001;  16 1625-1631
    CrossrefPubMedGoogle Scholar
  • 57 Nolan J, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subject treated with troglitazone.  N Engl J Med. 1994;  331 1188-1193
    CrossrefPubMedGoogle Scholar
  • 58 Norman R J, Masters L, Milner C R, Wang J X, Davies M J. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome.  Hum Reprod. 2001;  16 1995-1998
    CrossrefPubMedGoogle Scholar
  • 59 Paradisi G, Steinberg H O, Hempfling A, Cronin J, Hook G, Shepard M K, Baron A D. Polycystic ovary syndrome is associated with endothelial dysfunction.  Circulation. 2001;  3 1410-1415
    PubMedGoogle Scholar
  • 60 Peppard H R, Marfori J, Iuorno M J, Nestler J E. Prevalence of polycystic ovary syndrome among premenopausalen women with type 2 diabetes.  Diabetes Care. 2001;  24 1050-1052
    PubMedGoogle Scholar
  • 61 Pierpoint T, McKeigue P M, Isaacs A J, Wild S H, Jacobs H S. Mortality of women with polycystic ovary syndrome at long-term follow-up.  J Clin Epidemiol. 1998;  51 581-586
    CrossrefPubMedGoogle Scholar
  • 62 Pirwany I R, Yates R WS, Cameron I T, Fleming R. Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.  Hum Reprod. 1999;  14 2963-2968
    CrossrefPubMedGoogle Scholar
  • 63 Reaven G M. Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
    CrossrefPubMedGoogle Scholar
  • 64 Reaven G M. Insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension. Parallels between human disease and rodent models.  Diabetes Care. 1991;  14 195-202
    PubMedGoogle Scholar
  • 65 Romualdi D, Guido M, Ciampelli M, Giuliani M, Leoni F, Perri C, Lanzone A. Selctive effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome.  Hum Reprod. 2003;  18 1210-1218
    PubMedGoogle Scholar
  • 66 Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron E L. Insulin resistance in patients with polycystic ovary syndrom is associated with elevated plasma homocysteine.  Hum Reprod. 2003;  18 721-727
    CrossrefPubMedGoogle Scholar
  • 67 Shobokshi A, Shaarawy M. Correction of insulin resistance and hyper-androgenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy.  J Soc Gynecol Investig. 2003;  10 99-104
    PubMedGoogle Scholar
  • 68 Stadtmauer L A, Toma S K, Riehl R M, Talbert L M. Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcome and is associated with modulation of the insulin-growth factors.  Fertil Steril. 2001;  75 505-509
    CrossrefPubMedGoogle Scholar
  • 69 Stadtmauer L A, Toma S K, Riehl R M, Talbert L M. Impact of metformin therapy on ovarian stimulation and outcome in “coasted” patients with polycystic ovary syndrom undergoing in-vitro fertilization.  Reprod Biomed Online. 2002;  5 112-116
    PubMedGoogle Scholar
  • 70 Talbott E, Clerici A, Berga S L, Kuller L, Guzick D, Detre K, Daniels T, Engberg R A. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study.  J Clin Epidemiol. 1998;  51 415-422
    CrossrefPubMedGoogle Scholar
  • 71 Talbott E, Guzieck D, Clerici A, Berga S, Detre K, Weimar K, Kuller L. Coronary heart disease risk factors in women with polycystic ovary syndrome.  Arterioscler Thromb Vasc Biol. 1995;  15 821-826
    CrossrefPubMedGoogle Scholar
  • 72 Talbott E O, Guzieck D S, Suton-Tyrrell K, McHugh-Pemu K P, Zborowski J V, Remsberg K E, Kuller L H. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.  Arterioscler Thromb Vasc Biol. 2000;  20 2414-2421
    PubMedGoogle Scholar
  • 73 Tuomilehto J, Lindstrom J, Eriksson J G, Valle T T, Hamalainen H, Ilanne-Parrika P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rasta M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.  N Engl J Med. 2001;  344 1343-1350
    CrossrefPubMedGoogle Scholar
  • 74 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. 1999;  96 8573-8578
    CrossrefPubMedGoogle Scholar
  • 75 Vandermolen D T, Ratts V S, Evans W S, Stovall D W, Kauma S W, Nestler J E. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.  Fertil Steril. 2001;  75 310-315
    CrossrefPubMedGoogle Scholar
  • 76 Velazquez E M, Mendoza S, Hamer T, Sosa F, Glueck C J. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy.  Metabolism. 1994;  43 647-654
    CrossrefPubMedGoogle Scholar
  • 77 Velazquez E, Costa A, Mendoza S G. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.  Obstet Gynecol. 1997;  90 392-395
    PubMedGoogle Scholar
  • 78 Vribikova J, Bicikova M, Tallova J, Hill M, Starka L. Homocysteine and steriods levels in metformin treated women with polycystic ovary syndrome.  Exp Clin Endocrinol Diabetes. 2002;  110 74-76
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Waterworth D M, Bennett S T, Gharani N, McCarthy M I, Hague S, Batty S, Conway G S, White D, Todd J A, Franks S, Williamson R. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome.  Lancet. 1997;  349 1771-1772
    PubMedGoogle Scholar
  • 80 Wild R A, Painter P C, Coulson P B, Carruth K B, Ranney G B. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1985;  61 946-951
    CrossrefPubMedGoogle Scholar
  • 81 Wild R A. Polycystic ovary syndrome: a risk for coronary artery disease?.  Am J Obstet Gynecol. 2002;  186 35-43
    CrossrefPubMedGoogle Scholar
  • 82 Wild R A. Long-term health consequences of PCOS.  Hum Reprod. 2002;  8 231-241
    PubMedGoogle Scholar
  • 83 Zheng Z, Li M, Lin Y, Ma Y. Effect of rosiglitazone on insulin resistance and hyperandrogenism in polycystic ovary syndrome.  Zhonghua Fu Chan Ke Za Zhi. 2002;  37 271-273
    PubMedGoogle Scholar

Dr. J. M. Weiss

Klinik für Frauenheilkunde und Geburtshilfe

Universitätsklinikum Schleswig-Holstein

Campus Lübeck

Ratzeburger Allee 160

23538 Lübeck

Phone: 04 51-5 00 21 55

Fax: 04 51-5 00 49 05

Email: jmweiss1@hotmail.com

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