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Geburtshilfe Frauenheilkd 2003; 63(7): 615-623
DOI: 10.1055/s-2003-41257
Übersicht

Georg Thieme Verlag Stuttgart · New York

Steroidhormone und Ovarialkarzinom: Risiken und Nutzen

Steroid Hormones and Ovarian Cancer: Risks and BenefitS. Krämer 1 , 2 , S. Ackermann 1 , P. A. Fasching 1 , H. Kreis 1 , U. Pöhls 1 , M. W. Beckmann 1
  • 1Klinik für Frauenheilkunde, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen
  • 2High-Tech-Clinic HC GmbH, Nürnberg
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Publication History

Eingang Manuskript: 3. Mai 2002 Eingang revidiertes Manuskript: 8. Juli 2002

Akzeptiert: 4. Juni 2003

Publication Date:
11 August 2003 (online)

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Zusammenfassung

Die Exposition mit Steroidhormonen beeinflusst das Karzinomrisiko von Zielorganen wie Brust, Endometrium und Ovar. Eine Vielzahl von epidemiologischen Studien unterstreicht die Zusammenhänge zwischen der ovariellen Hormonproduktion und dem Ovarialkarzinomrisiko. Die exogene Hormonapplikation in Form der oralen Kontrazeptiva und der Hormontherapie (HT) wird im Rahmen der Ovarialkarzinomprävention und als möglicher Risikofaktor für die Entstehung von Ovarialkarzinomen diskutiert. Aufgrund der vorliegenden Daten ist anzunehmen, dass die kombinierte Östrogen-Gestagen-Substitutionstherapie über längere Zeiträume die Erkrankungsinzidenzen an Ovarialkarzinomen - im Gegensatz zur reinen Östrogensubstitution - nicht signifikant erhöht. Die Hormontherapie wird bei Patientinnen mit Karzinomen oftmals als kontraindiziert angesehen. In mehreren Studien konnte allerdings durch den Einsatz der HT eine Verlängerung des Rezidiv- und Gesamtüberlebens und eine Verbesserung der Lebensqualität von Patientinnen mit Ovarialkarzinom gezeigt werden. Aussagen über die Möglichkeit und Unbedenklichkeit einer HT bei Patientinnen mit Ovarialkarzinom bleiben allerdings weiterhin individuell, bis weitere und größere randomisierte Studien vorliegen.

Abstract

The exposure to steroid hormones during different phases of a woman's life can influence the risk of cancer in the main target organs, i.e. the breast, endometrium and ovary. Numerous epidemiological studies report associations between markers of ovarian hormone production and ovarian cancer risk. In recent decades, also exogenous hormones - as in oral contraceptives and hormonal therapy - have been implicated as risk factors for ovarian cancer and also as preventive agents. Despite this substantial body of epidemiological evidence there is only limited indication that steroid hormones seem to play a growth regulating role in ovarian cancer.

Hormonal therapy (HT) is discussed to have positive and negative effects. Cancer fear is an important obstacle to use of HT. From our literature review, there is a weak association between HT and ovarian cancer risk. Individual risk of cancer should be considered before HT use. The second issue in this review is HT in patients with ovarian cancer. HT is considered by many physicians to be contraindicated in patients with cancer. However, there is evidence that HT in selected ovarian cancer patients may be of benefit for survival and quality of life.

Schlüsselwörter

Hormontherapie - Ovarialkarzinomrisiko - genetische Prädisposition - Prävention

Key words

Hormonal therapy (HT) - ovarian cancer risk - genetic predisposition - prevention

Literatur

  • 1 Adami H O, Persson I, Hoover R. Risk of cancer in women receiving hormone replacement therapy.  Int J Cancer. 1989;  44 833-839
    CrossrefPubMedGoogle Scholar
  • 2 Adami H O, Hsieh C C, Lambe M. Parity, age at first childbirth, and risk of ovarian cancer.  Lancet. 1994;  344 1250-1254
    CrossrefPubMedGoogle Scholar
  • 3 Beckmann M W, Niederacher D, Goecke T O. et al . Hochrisikofamilien mit Mamma- und Ovarialkarzinomen: Möglichkeiten der Beratung, genetischen Analyse und Früherkennung.  Deutsches Ärzteblatt. 1997;  94 A161-A167 Deutsches Ärzteblatt. 1997;  94 B1572-B1574 (Diskussion)
    PubMedGoogle Scholar
  • 4 Beckmann M W, Timmermann T. Gibt es ein Populations- oder ein Risikogruppen-Screening für das Ovarialkarzinom?.  Gynäkologe. 1997;  30 85-91
    CrossrefPubMedGoogle Scholar
  • 5 Beckmann M W, Kuschel B, Schmutzler R K. Hereditäre Karzinomsyndrome in der Frauenheilkunde.  Gynäkologe. 1998;  31 1039-1045
    CrossrefPubMedGoogle Scholar
  • 6 Beral V, Darby S, Cuzick J. Homone replacement therapy and ovarian cancer (letter).  BMJ. 1991;  302 790
    PubMedGoogle Scholar
  • 7 Beral V, Hermon C, Kay C. Mortality associated with oral contraceptives use: 25 year follow up of cohort of 46, 000 women from Royal College of General Practitioners' oral contraceptives study.  British Medical J. 1999;  318 96-100
    PubMedGoogle Scholar
  • 8 Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study.  Br J Cancer. 1989;  60 592-598
    PubMedGoogle Scholar
  • 9 Bourne T H, Campell S, Reynolds K M. et al . Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.  Br Med J. 1993;  306 1025-1029
    PubMedGoogle Scholar
  • 10 Boyd J, Rubin S C. Hereditary ovarian cancer: molecular genetics and clinical implications.  Gynecologic Oncology. 1997;  64 196-206
    CrossrefPubMedGoogle Scholar
  • 11 Bruckner H W, Motwani B T. Treatment of advanced refractory ovarian carcinoma with a gonadotropin-releasing hormone analogue.  Am J Obstet Gynecol. 1989;  161 1216-1219
    PubMedGoogle Scholar
  • 12 Carg P. Hormon replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis.  Gynecol. 1998;  32 472-479
    PubMedGoogle Scholar
  • 13 Casagrande J T, Louie E W, Pike M C, Roy S, Rock R K, Henderson B E. Incessant ovulation ovarian cancer?.  Lancet. 1979;  2 (8135) 170-172
    PubMedGoogle Scholar
  • 14 Coughlin S. A meta-analysis of estrogen replacement therapy and the risk of epithelial ovarian cancer.  J Clin Epidemiol. 2000;  53 367-385
    CrossrefPubMedGoogle Scholar
  • 15 Cramer D W, Hutchison G B, Welch W R. et al . “Determinants of ovarian cancer risk. I. Reproductive experiences and family history”.  J Natl Cancer Inst. 1983;  71 711-716
    PubMedGoogle Scholar
  • 16 Cramer D W, Welch W R. Determinants of ovarian cancer risk. II. Interferences regarding pathogenesis.  J Natl Cancer Inst. 1983;  71 717-720
    PubMedGoogle Scholar
  • 17 DePriest P D, Van Nagell J R, Gallion H H. et al . Ovarian cancer screening in asymptomatic postmenopausal women.  Gynecol Oncol. 1993;  51 205-209
    CrossrefPubMedGoogle Scholar
  • 18 Eeles R A, Tan S, Wiltshaw E. Hormone replacement therapy and survival after surgery for ovarian cancer.  BMJ. 1991;  302 259
    CrossrefPubMedGoogle Scholar
  • 19 Emons G, Ortmann O, Schulz K D. Rolle der endokrinen Therapie beim Ovarialkarzinom.  Gynäkologe. 1993;  26 123-130
    PubMedGoogle Scholar
  • 20 Emons G, Ortmann O, Schulz K D. Ovulationsinduktion und Karzinomrisiko.  Gynäkologe. 1996;  29 291-299
    PubMedGoogle Scholar
  • 21 Fathalla M F. Incessant ovulation - a factor in ovarian neoplasie?.  Lancet. 1971;  2 (7716) 163-166
    PubMedGoogle Scholar
  • 22 Fitzgerald C T, Elstein M, Mansel R E. Hormone replacement therapy and malignancy.  Br J Obstet Gynaecol. 1993;  100 408
    PubMedGoogle Scholar
  • 23 Schrag D, Kuritz K M, Garber J E, Weeks J C. Decision analysis - effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations.  N Engl J Med. 1997;  336 1465-1471
    CrossrefPubMedGoogle Scholar
  • 24 Franceschi S, La Vecchia C, Helmrich S P, Mangioni C, Tononi G. Risk factors for epithelial ovarian cancer in Italy.  Am J Epidemiol. 1982;  115 714-719
    PubMedGoogle Scholar
  • 25 Grady D, Gebretsadik T, Kerlikowske K, Ermster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis.  Obstet Gynecol. 1995;  85 304-313
    CrossrefPubMedGoogle Scholar
  • 26 Grover S, Quinn M A, Weideman P, Koh K. Factors influencing serum Ca 125 levels in normal women.  Obstet Gynecol. 1992;  79 511-514
    PubMedGoogle Scholar
  • 27 Guidozzi F, Daponte A. Estrogen replacement therapy for ovarian carcinoma survivors: a randomized controlled trial.  Cancer. 1999;  86 1013-1018
    CrossrefPubMedGoogle Scholar
  • 28 Harding M, Cowan S, Hole D, Cassidy L, Kitekener H, Davis J, Leake R. Estrogen and progesterone receptors in ovarian cancer.  Cancer. 1990;  65 486-491
    PubMedGoogle Scholar
  • 29 Hartge P, Hoover R, Mc Gowan L, Lesker L, Norris H J. Menopause and ovarian cancer.  Am J Epidemiol. 1988;  188 990-998
    PubMedGoogle Scholar
  • 30 Hatch K D, Beecham J B, Blessing J A, Creasman W T. Responsiveness of patients with advanced ovarian carcinoma to tamoxifen.  Cancer. 1991;  302 269-272
    PubMedGoogle Scholar
  • 31 Hempling R E, Wong C, Piver M S. Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study.  Obstet Gynecol. 1997;  89 1012
    CrossrefPubMedGoogle Scholar
  • 32 Hildreth N G, Keksey J L, Li Volsi. An epidemiologic study of epithelial carcinoma of the ovary.  Am J Epidemiol. 1981;  114 399
    PubMedGoogle Scholar
  • 33 Hoover R, Gray Sr L A. Fraumeni JF Jr. Stilboestrol (diethylstilbestrol) and the risk of ovarian cancer.  Lancet. 1977;  2 533
    PubMedGoogle Scholar
  • 34 Hunt K, Vessey M, McPherson K, Coleman M. Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy.  Br J Obstet Gynaecol. 1987;  94 620-635
    PubMedGoogle Scholar
  • 35 Jacobs I. Genetic, biochemical, and multimodal approaches to screening for ovarian cancer.  Gynecol Oncol. 1994;  55 22-27
    CrossrefPubMedGoogle Scholar
  • 36 Jäger W, Dittrich R, Recabarren S, Wildt L, Lang N. Induction of ovarian tumors by endogenous gonadotropins in rats bearing intrasplenic ovarian grafts.  Tumor Biol. 1995;  16 268-280
    PubMedGoogle Scholar
  • 37 Jäger W, Wildt L, Lang N. Some observations on the effect of a GnRH analog in ovarian cancer.  Eur J Obstet Gynecol Reprod Biol. 1989;  32 137-148
    CrossrefPubMedGoogle Scholar
  • 38 Kaufman D W, Kelly J P, Welch W R. Noncontraceptive estrogen use and the epithelial ovarian cancer.  Am J Epidemiol. 1989;  130 1142
    PubMedGoogle Scholar
  • 39 Kraemer S, Leeker M, Jäger W. Gonadotropin levels in ovarian cyst fluids: a predictor of malignancy?.  Int J Biol Markers. 1998;  13 165-168
    PubMedGoogle Scholar
  • 40 Kraemer S, Jaeger W, Lang N. Growth regulation effects or gonadotropin induced steroidogenic response in human ovarian cancer.  Anticancer Research. 2001;  21 2005-2010
    PubMedGoogle Scholar
  • 41 Lacey J V, Mink P J, Lubin J H, Sherman M E, Troisi R, Hartge P, Schatzkin A, Schairer C. Menopausal hormone replacement therapy and risk of ovarian cancer.  JAMA. 2002;  288 334-341
    CrossrefPubMedGoogle Scholar
  • 42 La Vecchia C, Franceschi S. Noncontraceptive estrogen use and the occurrence of ovarian cancer (letter).  J Natl Cancer Inst. 1982;  69 95
    PubMedGoogle Scholar
  • 43 Bojd J, Aubin S C. Hereditary ovarian cancer: molecular genetics and clinical implications.  Gynecol Oncol. 1997;  64 196-206
    CrossrefPubMedGoogle Scholar
  • 44 NIH Consensus Conference (1995) Ovarian cancer . Screening, treatment, and follow-up.  JAMA. 1995;  273 491-497
    CrossrefPubMedGoogle Scholar
  • 45 Nguyen H N, Averette H E, Janicek M. Ovarian carcinoma.  Cancer. 1994;  74 545-555
    PubMedGoogle Scholar
  • 46 Parazzini F, La Vecchia C, Negri E. Determinants of estrogen replacement therapy use in in northern Italy.  Rev Epidemiol Sante Publique. 1993;  41 53
    PubMedGoogle Scholar
  • 47 Parazzini F, La Vecchia C, Negri E. Estrogen replacement therapy and ovarian cancer risk.  Int J Cancer. 1994;  57 135-136
    PubMedGoogle Scholar
  • 48 Persson I. Cancer risk in women receiving estrogen-progestin replacement therapy.  Maturiatas. 1996;  23 (Suppl) 37
    PubMedGoogle Scholar
  • 49 Pfleiderer A. Möglichkeiten des Tumor-Screenings in der Gynäkologie.  Der Frauenarzt. 1995;  8 893-900
    PubMedGoogle Scholar
  • 50 Piver M S, Baker T R, Jishi M F, Sandecki A M, Tsukada Y, Natarajan N, Mettlin C J, Blake C A. Familial ovarian cancer.  Cancer. 1993;  71 582-588
    PubMedGoogle Scholar
  • 51 Polychronopoulou A, Tzonou A, Hsich C C, Kapinis G, Rebelakos A, Toupadaki N. Reproductive variables, tabacco, ethanol, coffee and somatometry as a risk factor for ovarian cancer.  Int J Cancer. 1993;  55 402-407
    PubMedGoogle Scholar
  • 52 Purdie D M, Bain C J, Siskind V. Hormone replacement therapy and the risk of epithelial ovarian cancer.  Br J Cancer. 1999;  81 559
    CrossrefPubMedGoogle Scholar
  • 53 Rao R B, Slotman B J. Endocrine factors in common epithelial ovarian cancer.  Endocr Rev. 1991;  12 14-17
    PubMedGoogle Scholar
  • 54 Risch H A. Estrogen replacement therapy and the risk of epithelial ovarian cancer.  Gynecol Oncol. 1996;  63 254
    CrossrefPubMedGoogle Scholar
  • 55 Rodriguez C, Calle E E, Coates R J. Estrogen replacement therapy and fatal ovarian cancer.  Am J Epidemiol. 1995;  141 828
    PubMedGoogle Scholar
  • 56 Rodriguez C, Patel A V, Fjacob E J, Thurn M J. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women.  JAMA. 2001;  285 1460-1465
    CrossrefPubMedGoogle Scholar
  • 57 Rubin S C, Benjamin I, Behbakht K. Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1.  N Engl J Med. 1996;  335 1413-1416
    CrossrefPubMedGoogle Scholar
  • 58 Schwartz P E, Chambers J T, Kohorn E J, Chambers S K, Weitzman H, Voynick I M, McLusky N, Naftolin F. Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer.  Cancer. 1989;  63 1074-1077
    PubMedGoogle Scholar
  • 59 Shirey D R, Kavanagh J J, Gershenson D M, Freedman R S, Copeland L J, Jones L A. Tamoxifen therapy of epithelial ovarian cancer.  Obstet Gynecol. 1985;  66 575-580
    PubMedGoogle Scholar
  • 60 Slevin M L, Harvey V J, Osborne R J, Shepherd J H, Williams C J, Mead G M. A phase II study of tamoxifen in ovarian cancer.  Eur J Cancer Clin Oncol. 1986;  22 309-312
    CrossrefPubMedGoogle Scholar
  • 61 Slotman B J, Nauta J JP, Rao B R. Survival of ovarian cancer patients: Apart from stage and grade, tumor progesterone receptor is a prognostic indicator.  Cancer. 1990;  66 740-742
    PubMedGoogle Scholar
  • 62 Tzonou A, Day N E, Trichopoulous D, Walker A, Saliaraki M, Papapostoulou M, Polychronopoulou A. The epidemiology of ovarian cancer in Greece.  Eur J Cancer Clin Oncol. 1984;  20 1045-1052
    CrossrefPubMedGoogle Scholar
  • 63 Vessey M P, Painter R. Endometrial and ovarian cancer and oral contraceptives findings in a large cohort study.  Br J Cancer. 1995;  71 1340-1342
    PubMedGoogle Scholar
  • 64 Weiss N S, Lyon J L, Krishnamurthy S. Noncontraceptive estrogen use and the occurrence of ovarian cancer.  J Natl Cancer Inst. 1982;  68 95
    PubMedGoogle Scholar
  • 65 Whittemore A S, Harris R, Itnyre J, Halpern J. The Collaborative Ovarian Cancer Group . Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. I. Methods.  Am J Epidemiol. 1992;  136 1184-1203
    PubMedGoogle Scholar
  • 66 Whittemore A S, Harris R, Itnyre for the Collaborative Ovarian Cancer Group J. (1992) . Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women.  Am J Epidemiol. 1992;  136 1184-1203
    PubMedGoogle Scholar
  • 67 Wu M L, Whittemore A S, Paffenbarger Jr R S. Personal and environmental characteristics related to epithelial ovarian cancer I. Reproductive and menstrual events and oral contraceptive use.  Am J Epidemiol. 1988;  128 1216
    PubMedGoogle Scholar
  • 68 Yasuda M, Kurabayashi T, Yamamoto Y, Fujimaki T, Oda K, Tanaka K. Effect of hormone replacement therapy on the bone and lipid metabolism in women oophorectomized for treatment of gynecologic malignancies.  Int J Gynaecol Obstet. 1994;  47 151
    CrossrefPubMedGoogle Scholar
  • 69 Zimniski S J, Grada R E, Fendl K, Peterson C M. Endocrine characterization of a human ovarian carcinoma (BG-1) established in nude mice.  Steroids. 1998;  54 593-606
    PubMedGoogle Scholar
  • 70 Beckmann M W, Braendle W, Brucker C, Dören M, Emons G, Geisthövel F, Kiesel L, König K, Naß-Griegoleit I, Ortmann (federführend) O, Rabe T, Windler E. Konsensus-Empfehlungen zur Hormontherapie (HT) im Klimakterium und in der Postmenopause, DGGG.  Geburtsh Frauenheilk. 2003;  63 209-212
    Article in Thieme ConnectPubMedGoogle Scholar

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