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Dtsch Med Wochenschr 2002; 127(18): 971-977
DOI: 10.1055/s-2002-26735
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© Georg Thieme Verlag Stuttgart · New York

Polyzystisches Ovarsyndrom und metabolisches Syndrom

Polycystic ovary syndrome and metabolic syndromeC. J. Auernhammer, D. Engelhardt, K. G. Parhofer
  • 1Medizinische Klinik II Großhadern, Klinikum der Ludwig Maximilians Universität München
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Publication History

15.1.2001

19.3.2002

Publication Date:
02 May 2002 (online)

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Das Krankheitsbild des polyzystischen Ovarsyndroms (PCOS) ist definiert durch eine primär ovarielle Hyperandrogenämie und chronische Anovulation. Mit einer Prävalenz von 5-7 % stellt das PCOS eine der häufigsten gynäkologisch-endokrinologischen Erkrankungen dar. Als ein wesentlicher pathogenetischer Faktor besteht häufig eine Insulinresistenz. Überdurchschnittlich häufig finden sich auch eine gestörte Glukosetoleranz oder ein Diabetes mellitus Typ 2, eine Adipositas oder ein metabolisches Syndrom. Die Assoziation von kardiovaskulären Risikofaktoren legt eine erhöhte kardiovaskuläre Morbidität und Mortalität nahe. Aktuelle klinische Studien zeigen positive Effekte von Gewichtsreduktion, Metformin und Insulinsensitizern nicht nur auf die Insulinresistenz und das metabolische Syndrom, sondern auch auf die Hyperandrogenämie und die ovarielle Dysfunktion. Ziel dieser Übersichtsarbeit ist es, die zentrale Rolle der Insulinresistenz in der Pathogenese des PCOS darzustellen und aktuelle Therapiemöglichkeiten der Insulinresistenz beim PCOS zu diskutieren.

Literatur

  • 1 Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?.  Fertil Steril. 1996;  65 946-949
    Search in Google Scholar
  • 2 Asuncion M, Calvo R M, San Millan J L, Sancho J, Avila S, Escobar-Morreale H F. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.  J Clin Endocrinol Metab. 2000;  85 2434-2448
    Search in Google Scholar
  • 3 Azziz R, Ehrmann D, 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
    Search in Google Scholar
  • 4 Batukan C, Baysal B. Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome.  Arch Gynecol Obstet. 2001;  265 124-127
    Search in Google Scholar
  • 5 Cagnacci A, Arangino S, Renzi A, Cagnacci P, Volpe A. Insulin sensitivity in women: a comparison among values derived from intravenous glucose tolerance tests with different sampling frequency, oral glucose tolerance test or fasting.  Eur J Endocrinol. 2001;  145 281-287
    Search in Google Scholar
  • 6 Ciampelli M, Fulghesu A M, Cucinelli F, Pavone V, Ronsisvalle E, Guido M, Caruso A, Lanzone A. Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome.  Metabolism. 1999;  48 167-172
    Search in Google Scholar
  • 7 Clayton R N, Ogden V, Hodgkinson J, Worswick L, Rodin D A, Dyer S, Meade T W. How common are polycystic ovaries in normal women and what is their significance for the fertility of the population?.  Clin Endocrinol (Oxf). 1992;  37 127-134
    Search in Google Scholar
  • 8 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
    Search in Google Scholar
  • 9 De Leo V, La Marca A, Orvieto R, Morgante G. Effect of metformin on insulin-like growth factor (IGF) I and IGF-binding protein I in polycystic ovary syndrome.  J Clin Endocrinol Metab. 2000;  85 1598-1600
    Search in Google Scholar
  • 10 Dewailly D. Definition and significance of polycystic ovaries.  Baill Clin Obstet Gynaecol. 1997;  11 349-368
    Search in Google Scholar
  • 11 Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome.  Eur J Endocrinol. 1998;  138 269-74
    Search in Google Scholar
  • 12 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 4666-4673
    Search in Google Scholar
  • 13 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.  Endocr Rev. 1997;  18 774-800
    Search in Google Scholar
  • 14 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
    Search in Google Scholar
  • 15 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 steroidogenesis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 524-530
    Search in Google Scholar
  • 16 Glueck C J, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91 %) previously amenorrheic women with the polycystic ovary syndrome.  Metabolism. 1999;  48 511-519
    Search in Google Scholar
  • 17 Glueck C J, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS).  J Adolesc Health. 2001;  29 160-169
    Search in Google Scholar
  • 18 Hoeger K. Obesity and weight loss in polycystic ovary syndrome.  Obstet Gynecol Clin North Am. 2001;  28 85-97
    Search in Google Scholar
  • 19 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
    Search in Google Scholar
  • 20 Ibanez L, Valls C, Potau N, Marcos M V, de Zegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche.  J Clin Endocrinol Metab. 2000;  85 3526-3530
    Search in Google Scholar
  • 21 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
    Search in Google Scholar
  • 22 Jakubowicz D J, Seppala M, Jakubowicz S, Rodriguez-Armas O, Rivas-Santiago A, Koistinen H, Koistinen R, Nestler J E. Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 2001;  86 1126-1133
    Search in Google Scholar
  • 23 Kahsar-Miller M D, Nixon C, Boots L R, Go R C, Azziz R. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS.  Fertil Steril. 2001;  75 53-58
    Search in Google Scholar
  • 24 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 prospective study.  J Clin Endocrinol Metab. 1998;  83 3078-3082
    Search in Google Scholar
  • 25 Koivunen R, Laatikainen T, Tomas C, Huhtaniemi I, Tapanainen J, Martikainen H. The prevalence of polycystic ovaries in healthy women.  Acta Obstet Gynecol Scand. 1999;  78 137-141
    Search in Google Scholar
  • 26 Koivunen R M, Morin-Papunen L C, Ruokonen A, Tapanainen J S, Martikainen H K. Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin.  Hum Reprod. 2001;  16 2546-2551
    Search in Google Scholar
  • 27 Kolodziejczyk B, Duleba A J, Spaczynski R Z, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.  Fertil Steril. 2000;  73 1149-1154
    Search in Google Scholar
  • 28 Kowalska I, Kinalski M, Straczkowski M, Wolczyski S, Kinalska I. Insulin, leptin, IGF-I and insulin-dependent protein concentrations after insulin-sensitizing therapy in obese women with polycystic ovary syndrome.  Eur J Endocrinol. 2001;  144 509-515
    Search in Google Scholar
  • 29 la Marca A, Morgante G, Paglia T, Ciotta L, Cianci A, De Leo V. Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.  Fertil Steril. 1999;  72 985-989
    Search in Google Scholar
  • 30 la Marca A, Egbe T O, Morgante G, Paglia T, Cianci A, De Leo V, Ciani A. Metformin treatment reduces ovarian cytochrome P-450c17alpha response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome.  Hum Reprod. 2000;  15 21-23
    Search in Google Scholar
  • 31 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
  • 32 Michelmore K F, Balen A H, Dunger D B, Vessey M P. Polycystic ovaries and associated clinical and biochemical features in young women.  Clin Endocrinol (Oxf). 1999;  51 779-786
    Search in Google Scholar
  • 33 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
  • 34 Morin-Papunen L C, Koivunen R M, Ruokonen A, Martikainen H K. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome.  Fertil Steril. 1998;  69 691-696
    Search in Google Scholar
  • 35 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-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study.  J Clin Endocrinol Metab. 2000;  85 3161-3168
    Search in Google Scholar
  • 36 Nestler J E, Jakubowicz D J. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.  N Engl J Med. 1996;  335 617-623
    Search in Google Scholar
  • 37 Nestler J E, Jakubowicz D J. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens.  J Clin Endocrinol Metab. 1997;  82 4075-4079
    Search in Google Scholar
  • 38 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
  • 39 Nestler J E, Stovall D, AkhterN, Iuorno M J, Jakubowicz D J. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome.  Fert Steril. 2002;  77 209-215
    Search in Google Scholar
  • 40 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
    Search in Google Scholar
  • 41 Parsanezhad M E, Alborzi S, Zarei A, Dehbashi S, Omrani G. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.  Int J Gynaecol Obstet. 2001;  75 43-50
    Search in Google Scholar
  • 42 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
  • 43 Pirwany I R, Yates R W, 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
    Search in Google Scholar
  • 44 Unluhizarci K, Kelestimur F, Bayram F, Sahin Y, Tutus A. The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 1999;  51 231-236
    Search in Google Scholar
  • 45 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
    Search in Google Scholar
  • 46 Velazquez E M, Mendoza S, Hamer T, Sosa F, G lueck 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
    Search in Google Scholar
  • 47 Velazquez E, Acosta A, Mendoza S G. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.  bstet Gynecol. 1997;  90 392-395
    Search in Google Scholar
  • 48 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
  • 49 Vrbikova J, Hill M, Starka L, Cibula D, Bendlova B, Vondra K, Sulcova J, Snajderova M. The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome.  Eur J Endocrinol. 2001;  144 619-628
    Search in Google Scholar
  • 50 Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study.  Clin Endocrinol (Oxf). 2000;  52 595-600
    Search in Google Scholar

Dr. med. Christoph J. Auernhammer

Medizinische Klinik II, Klinikum der Ludwig-Maximilians-Universität, Standort Grosshadern

Marchioninistr. 15

81377 München

Phone: +49/89/70950

Fax: +49/89/7004418

Email: Christoph.Auernhammer@med2.med.uni-muenchen.de