Frauenheilkunde up2date 2014; 8(4): 251-262
DOI: 10.1055/s-0033-1357970
Allgemeine Gynäkologie und gynäkologische Onkologie
Georg Thieme Verlag KG Stuttgart · New York

Hormonsubstitution nach Ovarialkarzinomen und Borderline-Tumoren des Ovars

Gideon Sartorius
,
Céline Montavon
,
Marcus Vetter
,
Viola Heinzelmann-Schwarz
Further Information

Publication History

Publication Date:
29 August 2014 (online)

Kernaussagen

Trotz Optimierung der etablierten Therapiekonzepte bleibt das Ovarialkarzinom das gynäkologische Malignom mit der höchsten Mortalität. Der wesentlichste Prognosefaktor für Rezidivfreiheit und Überleben ist die optimale operative Reduktion der Tumormasse, das sog. Tumordebulking. Zur Standardtherapie gehört neben anderen Maßnahmen die beidseitige Adnexektomie, was bei prä- und perimenopausalen Frauen durch den sofortigen Östrogenabfall zu massiven klimakterischen Beschwerden führen kann. Viele dieser Frauen könnten von einer Hormonsubstitution profitieren, verzichten aber darauf aus Furcht vor hormoninduzierter Tumorproliferation. Tatsächlich erlaubt die aktuelle Datenlage keine klare Äußerung zur Bedenkenlosigkeit einer solchen Substitutionsbehandlung. Auf der einen Seite gibt es epidemiologische und molekularbiologische Untersuchungen, die die Hormonabhängigkeit von Ovarialkarzinomen dokumentieren [5], andererseits sind die oben dargelegten klinischen Studien zu dieser Fragestellung relativ beruhigend – obwohl der Evidenzgrad aufgrund der Studiendesigns nicht genügend ist.

Wir empfehlen deswegen nach wie vor Zurückhaltung bei der Verschreibung einer Hormonsubstitution und empfehlen bei Hormonausfallerscheinungen als Ersttherapie SSRI/SNRI oder ggf. eine Gestagen-Monotherapie. Bei fehlender Wirkung dieser Behandlung verschreiben wir aber eine Hormonsubstitution nach entsprechender Aufklärung über die relativ beruhigende Datenlage.

 
  • Literatur

  • 1 Loprinzi CL, Levitt R, Barton D et al. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7. J Clin Oncol 2006; 24: 1409-1414
  • 2 Farish E, Barnes JF, OʼDonoghue F et al. The role of megestrol acetate as an alternative to conventional hormone replacement therapy. Climacteric 2000; 3: 125-134
  • 3 Richelson LS, Wahner HW, Melton 3rd LJ et al. Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med 1984; 311: 1273-1275
  • 4 Colditz GA, Willett WC, Stampfer MJ et al. Menopause and the risk of coronary heart disease in women. N England J Med 1987; 316: 1105-1110
  • 5 Simpkins F, Garcia-Soto A, Slingerland J. New insights on the role of hormonal therapy in ovarian cancer. Steroids 2013; 78: 530-537
  • 6 Lhommé C, Delaloge S, Gonçalves E et al. [Are there any arguments against hormone replacement therapy after treatment of ovarian adenocarcinoma?]. Bull Cancer 1997; 84: 981-986
  • 7 Haring J, Schuler S, Lattrich C et al. Role of estrogen receptor beta in gynecological cancer. Gyn Oncol 2012; 127: 673-676
  • 8 Fahlen M, Fornander T, Johansson H et al. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer 2013; 49: 52-59
  • 9 Crum CP, Drapkin R, Miron A et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opinion Obste Gynecol 2007; 19: 3-9
  • 10 Loprinzi CL, Michalak JC, Quella SK et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med 1994; 331: 347-352
  • 11 Bertelli G, Venturini M, Del Mastro L et al. Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study. Ann Oncol 2002; 13: 883-888
  • 12 Schiff I, Tulchinsky D, Cramer D et al. Oral medroxyprogesterone in the treatment of postmenopausal symptoms. J Am Med Assoc 1980; 244: 1443-1445
  • 13 Trope CG, Kaern J, Davidson B. Borderline ovarian tumours. Best Pract Res Clin Obstet Gynecol 2012; 26: 325-336
  • 14 Morice P, Uzan C, Fauvet R et al. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol 2012; 13: e103-115
  • 15 Trillsch F, Mahner S, Woelber L et al. Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study. Ann Oncol 2014; 25: 1320-1327
  • 16 Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer – shifting the paradigm. Hum Pathol 2011; 42: 918-931
  • 17 Tsilidis KK, Allen NE, Key TJ et al. Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 2011; 105: 1436-1442
  • 18 Beral V, Doll R, Hermon C et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23257 women with ovarian cancer and 87303 controls. Lancet 2008; 371: 303-314
  • 19 Jordan SJ, Siskind V, Green AC et al. Breastfeeding and risk of epithelial ovarian cancer. Cancer Causes Control 2010; 21: 109-116
  • 20 Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 1992; 136: 1184-1203
  • 21 Kaufman DW, Kelly JP, Welch WR et al. Noncontraceptive estrogen use and epithelial ovarian cancer. Am J Epidemiol 1989; 130: 1142-1151
  • 22 Sit AS, Modugno F, Weissfeld JL et al. Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma. Gynecol Oncol 2002; 86: 118-123
  • 23 Anderson GL, Judd HL, Kaunitz AM et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Womenʼs Health Initiative randomized trial. J Am Med Assoc 2003; 290: 1739-1748
  • 24 Tsilidis KK, Allen NE, Key TJ et al. Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition. Cancer Causes Control 2011; 22: 1075-1084
  • 25 Beral V, Bull D, Green J et al. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007; 369: 1703-1710
  • 26 Morch LS, Lokkegaard E, Andreasen AH et al. Hormone therapy and ovarian cancer. J Am Med Assoc 2009; 302: 298-305
  • 27 Greiser CM, Greiser EM, Doren M. Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis. Hum Reprod Update 2007; 13: 453-463
  • 28 Zhou B, Sun Q, Cong R et al. Hormone replacement therapy and ovarian cancer risk: a meta-analysis. Gynecol Oncol 2008; 108: 641-651
  • 29 Santen RJ, Allred DC, Ardoin SP et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95: s1-s66
  • 30 Rodriguez C, Patel AV, Calle EE et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. J Am Med Assoc 2001; 285: 1460-1465
  • 31 Mascarenhas C, Lambe M, Bellocco R et al. Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival. Int J Cancer 2006; 119: 2907-2915
  • 32 Hein A, Thiel FC, Bayer CM et al. Hormone replacement therapy and prognosis in ovarian cancer patients. Eur J Cancer Prevent 2013; 22: 52-58
  • 33 Pearce CL, Chung K, Pike MC et al. Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin. Cancer 2009; 115: 531-539
  • 34 Colombo N, Chiari S, Maggioni A et al. Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy. Gynecol Oncol 1994; 55: S47-S51
  • 35 Guidozzi F, Daponte A. Estrogen replacement therapy for ovarian carcinoma survivors: A randomized controlled trial. Cancer 1999; 86: 1013-1018
  • 36 Ursic-Vrscaj M, Bebar S, Zakelj MP. Hormone replacement therapy after invasive ovarian serous cystadenocarcinoma treatment: the effect on survival. Menopause 2001; 8: 70-75
  • 37 Eeles RA, Tan S, Wiltshaw E et al. Hormone replacement therapy and survival after surgery for ovarian cancer. BMJ 1991; 302: 259-262
  • 38 Wen Y, Huang H, Huang H et al. The safety of postoperative hormone replacement therapy in epithelial ovarian cancer patients in China. Climacteric 2013; 16: 673-681
  • 39 Prior JC, Nielsen JD, Hitchcock CL et al. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Clin Sci 2007; 112: 517-525
  • 40 Kimmick GG, Lovato J, McQuellon R et al. Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J 2006; 12: 114-122
  • 41 Joffe H, Guthrie KA, LaCroix AZ et al. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial. JAMA Intern Med 2014; 174: 1058-1066
  • 42 Nelson HD, Vesco KK, Haney E et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. J Am Med Assoc 2006; 295: 2057-2071
  • 43 Fathalla MF. Incessant ovulation – a factor in ovarian neoplasia?. Lancet 1971; 2: 163
  • 44 Schildkraut JM, Bastos E, Berchuck A. Relationship between lifetime ovulatory cycles and overexpression of mutant p 53 in epithelial ovarian cancer. J Natl Cancer Inst 1997; 89: 932-938
  • 45 Silva EG, Tornos C, Fritsche jr. HA et al. The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model. Modern Pathol 1997; 10: 879-883
  • 46 Sönnichsen AC, Lindlacher U, Richter WO et al. [Obesity, body fat distribution and the incidence of breast, cervical, endometrial and ovarian carcinomas]. Dtsch Med Wochenschr 1990; 115: 1906-1910
  • 47 Olsen CM, Green AC, Nagle CM et al. Epithelial ovarian cancer: testing the ʼandrogens hypothesis . Endocr Relat Cancer 2008; 15: 1061-1068
  • 48 Rosenberg L, Palmer JR, Zauber AG et al. A case-control study of oral contraceptive use and invasive epithelial ovarian cancer. Am J Epidemiol 1994; 139: 654-661
  • 49 Landen jr. CN, Birrer MJ, Sood AK. Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol 2008; 26: 995-1005
  • 50 Siristatidis C, Sergentanis TN, Kanavidis P et al. Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer – a systematic review and meta-analysis. Hum Reprod Update 2013; 19: 105-123