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Hormonelle Therapie des polyzystischen Ovarsyndroms (PLOS)

Endocrine therapy of polycystic ovary syndrome

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Zusammenfassung

Zur endokrinen Therapie des heterogenen polyzystischen Ovarsyndroms (PCOS) stehen verschiedene Strategien zur Verfügung, die individuell auf die Patientin abgestimmt werden. Sind hyperandrogenämische Symptome wie Akne und Hirsutismus zu behandeln, wird antiandrogen therapiert und ein Zyklus etabliert. Orale Kontrazeptiva mit antiandrogenen Gestagenen sind dazu Mittel der ersten Wahl, in schwereren Fällen werden zusätzlich höher dosierte Gestagene eingesetzt. Bei Kinderwunsch erfolgt eine ovarielle Stimulation, ideal mit niedrig dosiertem FSH. Die Risiken einer ovariellen Überstimulation und höhergeradigen Mehrlingsschwangerschaft sind zu beachten. Zur Behandlung einer Insulinresistenz können Insulinsensitizer eingesetzt werden. Sie führen in einem großen Anteil der Patientinnen zu Ovulationen, durch Kombination mit einer ovariellen Stimulation lässt sich dieser Effekt noch weiter verbessern.

Abstract

Different strategies exist for endocrine therapy in the heterogenic polycystic ovary syndrome (PCOS), which can be customized for the individual patient. When hyperandrogenemic symptoms as acne and hirsutism are present, an antiandrogenic therapy and the establishment of a cycle is desired. Oral contraceptives containing antiandrogenic progestins are the drugs of choice, in severe cases additional progestin of a higher dosage is required. In case of infertility an ovarian stimulation is performed, preferably with low dose FSH. Care has to be taken to avoid ovarian hyperstimulation and higher grade multiples. To ameliorate insulin-resistance, insulin-sensitizers can be chosen. They will lead to ovulations in a significant number of patients. Combining them with an ovarian stimulation regimen will yield even higher ovulation rates.

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Literatur

  1. Franks S (1995) Polycystic ovary syndrome. N Engl J Med 333: 853–861

    Google Scholar 

  2. 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. Fertil Steril 81: 19–25

    Google Scholar 

  3. Geisthövel F (2003) A comment on the European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine consensus of the polycystic ovarian syndrome. Reprod Biomed Online 7: 602–605

    Google Scholar 

  4. Legro RS, Strauss JF (2002) Molecular progress in infertility: polycystic ovary syndrome. Fertil Steril 2002 78: 569–576

    Google Scholar 

  5. Schüring AN, Gromoll J, Sonntag B, Nieschlag E, Kiesel L, Greb RR (2004) A polymorphism in the androgen receptor gene (CAG repeats) is associated with polycystic ovary syndrome (PCOS). 60th annual ASRM-meeting, Philadelphia, USA

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

    Article  CAS  PubMed  Google Scholar 

  7. Dunaif A, Segal KR, Futterweit W, Dobrjansky A (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38: 1165–1174

    CAS  PubMed  Google Scholar 

  8. Burghen GA, Givens JR, Kitabchi AE (1980) Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 50: 113–116

    Google Scholar 

  9. Cattrall FR, Healy DL (2004) Long-term metabolic, cardiovascular and neoplastic risks with polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 185: 803–812

    Google Scholar 

  10. Legro RS (2003) Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rev 24: 302–312

    Google Scholar 

  11. Balen A (2001) Polycystic ovary syndrome and cancer. Hum Reprod Update 7: 522–525

    Google Scholar 

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

    Google Scholar 

  13. Farquhar C, Vandekerckhove P, Lilford R (2001) Laparoscopic „drilling“ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev 4: CD001122

    Google Scholar 

  14. Azziz R (2003) The evaluation and management of hirsutism. Obstet Gynecol 101: 995–1007

    Google Scholar 

  15. Van Vloten WA, van Haselen CW, van Zuuren EJ, Gerlinger C, Heithecker R (2002) The effect of 2 combined oral contraceptives containing either drospirenone or cyproterone acetate on acne and seborrhea. Cutis 69 [Suppl]: 2–15

    Google Scholar 

  16. Raudrant D, Rabe T (2003) Progestogens with antiandrogenic properties. Drugs 63: 463–492

    Google Scholar 

  17. Venturoli S, Marescalchi O, Colombo FM et al. (1999) A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of hirsutism. J Clin Endocrinol Metab 84: 1304–1310

    Google Scholar 

  18. Falsetti L, Gambera A, Platto C, Legrenzi L (2000) Management of hirsutism. Am J Clin Dermatol 1: 89–99

    Google Scholar 

  19. Dahlgren E, Landin K, Krotkiewski M, Holm G, Janson PO (1998) Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod 13: 2706–2711

    Google Scholar 

  20. Van der Spuy ZM, le Roux PA (2003) Cyproterone acetate for hirsutism. Cochrane Database Syst Rev 4: CD001125

    Google Scholar 

  21. Guido M, Romualdi D, Giuliani M, Suriano R, Selvaggi L, Apa R, Lanzone A (2004) Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab 89: 2817–2823

    Google Scholar 

  22. Shulman LP (2002) Safety and efficacy of a new oral contraceptive containing drospirenone. J Reprod Med 47 [Suppl]: 981–984

    Google Scholar 

  23. Farquhar C, Lee O, Toomath R, Jepson R (2003) Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev 4: CD000194

    Google Scholar 

  24. Shaw JC (2000) Low-dose adjunctive spironolactone in the treatment of acne in women: a retrospective analysis of 85 consecutively treated patients. J Am Acad Dermatol 43: 498–502

    Google Scholar 

  25. Moghetti P, Tosi F, Tosti A et al. (2000) Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab 85: 89–94

    Google Scholar 

  26. Kelestimur F, Sahin Y (1998) Comparison of Diane 35 and Diane 35 plus spironolactone in the treatment of hirsutism. Fertil Steril 69: 66–69

    Google Scholar 

  27. Muderris II, Bayram F, Guven M (2000) A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride(5 mg/d) in the treatment of hirsutism. Fertil Steril 73: 984–987

    Google Scholar 

  28. Muderris II, Bayram F, Guven M (2000) Treatment of hirsutism with lowest-dose flutamide (62.5 mg/day). Gynecol Endocrinol 14: 38–41

    Google Scholar 

  29. Ibanez L, Potau N, Marcos MV, de Zegher F (2000) Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. J Clin Endocrinol Metab 85: 3251–3255

    Google Scholar 

  30. Wild RA, Umstot ES, Andersen RN, Ranney GB, Givens JR (1983) Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol 146: 602–606

    Google Scholar 

  31. Carmina E, Rosato F, Janni A (1986) Increased DHEAS levels in PCO syndrome: evidence for the existence of two subgroups of patients. J Endocrinol Invest 9: 5–9

    Google Scholar 

  32. Azziz R, Black VY, Knochenhauer ES, Hines GA, Boots LR (1999) Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic ovary syndrome is not predicted by the basal dehydroepiandrosterone sulfate level. J Clin Endocrinol Metab 84: 946–950

    Google Scholar 

  33. Daly DC, Walters CA, Soto-Albors CE, Tohan N, Riddick DH (1984) A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril 41: 844–848

    Google Scholar 

  34. Bider D, Blankstein J, Levron J, Tur-Kaspa I (1997) Gonadotropins and glucocorticoid therapy for „low responders“ — a controlled study. J Assist Reprod Genet 14: 328–331

    Google Scholar 

  35. Carmina E, Wong L, Chang L, Paulson RJ, Sauer MV, Stanczyk FZ, Lobo RA (1997) Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound. Hum Reprod 12: 905–909

    Google Scholar 

  36. Acien P, Mauri M, Gutierrez M (1997) Clinical and hormonal effects of the combination gonadotrophin-releasing hormone agonist plus oral contraceptive pills containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone on polycystic ovarian disease-related hyperandrogenisms. Hum Reprod 12: 423–429

    Google Scholar 

  37. Lemay A, Faure N (1994) Sequential estrogen-progestin addition to gonadotropin-releasing hormone agonist suppression for the chronic treatment of ovarian hyperandrogenism: a pilot study. J Clin Endocrinol Metab 79: 1716–1722

    Google Scholar 

  38. Azziz R, Ochoa TM, Bradley EL, Potter HD, Boots LR (1995) Leuprolide and estrogen versus oral contraceptive pills for the treatment of hirsutism: a prospective randomized study. J Clin Endocrinol Metab 80: 3406–3411

    Google Scholar 

  39. Hughes E, Collins J, Vandekerckhove P (2000) Ovulation induction with urinary follicle stimulating hormone versus human menopausal gonadotropin for clomiphene-resistant polycystic ovary syndrome. Cochrane Database Syst Rev 2: CD000087

    Google Scholar 

  40. Nugent D, Vandekerckhove P, Hughes E, Arnot M, Lilford R (2000) Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev 4: CD000410

    Google Scholar 

  41. Olivennes F, Cunha-Filho JS, Fanchin R, Bouchard P, Frydman R (2002) The use of GnRH antagonists in ovarian stimulation. Hum Reprod Update 8: 279–290

    Google Scholar 

  42. Reissmann T, Felberbaum R, Diedrich K, Engel J, Comaru-Schally AM, Schally AV (1995) Development and applications of luteinizing hormone-releasing hormone antagonists in the treatment of infertility: an overview. Hum Reprod 10: 1974–1981

    Google Scholar 

  43. Elkind-Hirsch KE, Webster BW, Brown CP, Vernon MW (2003) Concurrent ganirelix and follitropin beta therapy is an effective and safe regimen for ovulation induction in women with polycystic ovary syndrome. Fertil Steril 79: 603–607

    Google Scholar 

  44. Kolibianakis E, Zikopoulos K, Albano C, Camus M, Tournaye H, Van Steirteghem A, Devroey P (2003) Reproductive outcome of polycystic ovarian syndrome patients treated with GnRH antagonists and recombinant FSH for IVF/ICSI. Reprod Biomed Online 7: 313–318

    Google Scholar 

  45. Hwang JL, Seow KM, Lin YH et al. (2004) Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod 19: 1993–2000

    Google Scholar 

  46. Ludwig M, Felberbaum RE, Devroey P et al. (2000) Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction. Arch Gynecol Obstet 264: 29–32

    Google Scholar 

  47. Cardone VS (2003) GnRH antagonists for treatment of polycystic ovarian syndrome. Fertil Steril 80 [Suppl]: S25–31

    Google Scholar 

  48. The ESHRE Capri Workshop (1997) Female infertility: treatment options for complicated cases. Hum Reprod 12: 1191–1196

    Google Scholar 

  49. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC (2002) A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 77: 91–97

    Google Scholar 

  50. Thompson LA, Barratt CL, Thornton SJ, Bolton AE, Cooke ID (1993) The effects of clomiphene citrate and cyclofenil on cervical mucus volume and receptivity over the periovulatory period. Fertil Steril 59: 125–129

    Google Scholar 

  51. Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME (1989) The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Obstet Gynecol 73: 187–190

    Google Scholar 

  52. Gonen Y, Casper RF (1990) Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 5: 670–674

    Google Scholar 

  53. Shoham Z, Borenstein R, Lunenfeld B, Pariente C (1990) Hormonal profiles following clomiphene citrate therapy in conception and nonconception cycles. Clin Endocrinol (Oxf) 33: 271–278

    Google Scholar 

  54. Kousta E, White DM, Franks S (1997) Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update 3: 359–365

    Google Scholar 

  55. Gysler M, March CM, Mishell DR, Bailey EJ (1982) A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril 37: 161–167

    Google Scholar 

  56. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC (1998) Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 83: 2361–2365

    Google Scholar 

  57. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R (1998) Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 338: 1876–1880

    Google Scholar 

  58. Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE (2001) 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 75: 310–315

    Google Scholar 

  59. George SS, George K, Irwin C, Job V, Selvakumar R, Jeyaseelan V, Seshadri MS (2003) Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial. Hum Reprod 18: 299–304

    Google Scholar 

  60. Sahin Y, Yirmibes U, Kelestimur F, Aygen E (2004) The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 113: 214–220

    Google Scholar 

  61. Ghazeeri G, Kutteh WH, Bryer-Ash M, Haas D, Ke RW (2003) Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome. Fertil Steril 79: 562–566

    Google Scholar 

  62. Van Der Meer M, Hompes PG, De Boer JA, Schats R, Schoemaker J (1998) Cohort size rather than follicle-stimulating hormone threshold level determines ovarian sensitivity in polycystic ovary syndrome. J Clin Endocrinol Metab 83: 423–426

    Google Scholar 

  63. Homburg R, Howles CM (1999) Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rationale, results, reflections and refinements. Hum Reprod Update 5: 493–499

    Google Scholar 

  64. Van Santbrink EJ, Fauser BC (1997) Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low dose step-up and step-down dose regimens. J Clin Endocrinol Metab 82: 3597–3602

    Google Scholar 

  65. Balasch J, Fabregues F, Creus M, Puerto B, Penarrubia J, Vanrell JA (2001) Follicular development and hormone concentrations following recombinant FSH administration for anovulation associated with polycystic ovarian syndrome: prospective, randomized comparison between low-dose step-up and modified step-down regimens. Hum Reprod 16: 652–656

    Google Scholar 

  66. Strowitzki T, Seehaus D, Korell M, Hepp H (1994) Low-dose follicle stimulating hormone for ovulation induction in polycystic ovary syndrome. J Reprod Med 39: 499–503

    Google Scholar 

  67. Tadokoro N, Vollenhoven B, Clark S, Baker G, Kovacs G, Burger H, Healy D (1997) Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction program. Hum Reprod 12: 1939–1944

    Google Scholar 

  68. Christin-Maitre S, Hugues JN; Recombinant FSH Study Group (2003) A comparative randomized multicentric study comparing the step-up versus step-down protocol in polycystic ovary syndrome. Hum Reprod 18: 1626–1631

    Google Scholar 

  69. Hughes JN, Cedrin-Durnerin I, Avril C, Bulwa S, Herve F, Uzan M (1996) Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome. Hum Reprod 11: 2581–2584

    Google Scholar 

  70. Mitwally MF, Casper RF (2002) Aromatase inhibition for ovarian stimulation: future avenues for infertility management. Curr Opin Obstet Gynecol 14: 255–263

    Google Scholar 

  71. Mitwally MF, Casper RF (2002) Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 77: 776–780

    Article  PubMed  Google Scholar 

  72. Mitwally MF, Biljan MM, Casper RF (2005) Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 192: 381–386

    Google Scholar 

  73. Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ (2002) Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril 77: 209–215

    Google Scholar 

  74. Lord JM, Flight IH, Norman RJ (2003) Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 3: CD003053

    Google Scholar 

  75. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R (1998) Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 338: 1876–1880

    Google Scholar 

  76. Pasquali R, Gambineri A, Biscotti D et al. (2000) 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 85: 2767–2774

    Google Scholar 

  77. Kocak M, Caliskan E, Simsir C, Haberal A (2002) Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril 77: 101–106

    Google Scholar 

  78. Stadtmauer LA, Toma SK, Riehl RM, Talbert LM (2001) Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors. Fertil Steril 75: 505–509

    Google Scholar 

  79. Stadtmauer LA, Wong BC, Oehninger S (2002) Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome — beyond ovulation induction. Hum Reprod 17: 3016–3026

    Google Scholar 

  80. Kumari AS, Haq A, Jayasundaram R, Abdel-Wareth LO, Al Haija SA, Alvares M (2005) Metformin monotherapy in lean women with polycystic ovary syndrome. Reprod Biomed online 10: 100–104

    Google Scholar 

  81. Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L (2000) Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril 73: 1149–1154

    Google Scholar 

  82. Kelly CJ, Gordon D (2002) The effect of metformin on hirsutism in polycystic ovary syndrome. Eur J Endocrinol 147: 217–221

    Google Scholar 

  83. Leidenberger FA, Strowitzki T, Ortmann O (2005) Klinische Endokrinologie für Frauenärzte, 3. Aufl. Springer, Berlin Heidelberg New York

  84. Berson DS, Chalker DK, Harper JC, Leyden JJ, Shalita AR, Webster GF (2003) Current concepts in the treatment of acne: report from a clinical roundtable. Cutis 72 [Suppl]: 5–13

    Google Scholar 

  85. Felberbaum RE, Ludwig M, Diedrich K (2000) Clinical application of GnRH-antagonists. Mol Cell Endocrinol 166: 9–14

    Google Scholar 

  86. Keck C, Neulen J, Breckwoldt M (1994) Ovarian hyperstimulation syndrome. Geburtshilfe Frauenheilkd 54: 315–320

    Google Scholar 

  87. Callahan TL, Hall JE, Ettner SL, Christiansen CL, Greene MF, Crowley WF (1994) The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 331: 244–249

    Google Scholar 

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  1. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster

    A. N. Schüring & L. Kiesel

  2. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum, Albert-Schweitzer-Straße 33, 48149, Münster

    A. N. Schüring

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Schüring, A.N., Kiesel, L. Hormonelle Therapie des polyzystischen Ovarsyndroms (PLOS). Gynäkologe 38, 333–341 (2005). https://doi.org/10.1007/s00129-005-1673-5

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