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Geburtshilfe Frauenheilkd 2012; 72(9): 809-818
DOI: 10.1055/s-0032-1315361
Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Chemotherapy-Induced Amenorrhea – An Update

Chemotherapieinduzierte Amenorrhö – ein Update
C. Liedtke
1   Gynecology and Obstetrics, Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster, Münster
,
L. Kiesel
1   Gynecology and Obstetrics, Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster, Münster
› Author Affiliations
Further Information

Publication History

received 07 August 2012
revised 19 August 2012

accepted 19 August 2012

Publication Date:
27 September 2012 (online)

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Chemotherapy-Induced Amenorrhea – An UpdateGeburtshilfe Frauenheilkd 2012; 72(09): e2-e2
DOI: 10.1055/s-0032-1328071

Abstract

Because of the heterogeneity in the definition of chemotherapy-induced amenorrhea (CIA) there are distinct differences in the literature with regard to its incidence as well as its dependence on various influencing factors. The occurrence of CIA varies greatly depending on the applied chemotherapy. The pathogenesis of CIA is especially based on a reduction of ovarian reserves. Various sonographic and biochemical factors can be used to exclude or confirm CIA. This is particularly important when an endocrine therapy with tamoxifen is not possible and the use of aromatase inhibitors is under consideration. CIA and especially the frequently thereby resulting early menopause can lead to pronounced restrictions in the quality of life of the affected patients, not least due to the resulting infertility. On the other hand, various studies have shown that CIA may have a positive prognostic significance. Thus, the identification of measures to prevent CIA (for example, through the use of GnRH analogues) is of particular importance.

Zusammenfassung

Aufgrund der Heterogenität in der Definition der chemotherapieinduzierten Amenorrhö (CIA) bestehen deutliche Unterschiede in der Literatur bez. ihrer Häufigkeit sowie der Abhängigkeit von verschiedenen Einflussfaktoren. Das Auftreten einer CIA variiert deutlich in Abhängigkeit von der angewandten Chemotherapie. Pathogenetisch liegt der CIA insbesondere eine Reduktion der ovariellen Reserve zugrunde. Verschiedene Ultraschall- und biochemische Faktoren können zum Ausschluss bzw. zur Feststellung einer CIA verwendet werden. Dies ist insbesondere dann wichtig, wenn eine endokrine Therapie mit Tamoxifen nicht möglich ist und der Einsatz von Aromatasehemmern erwogen wird. Eine CIA und insbesondere die daraus häufig resultierende vorzeitige Menopause können zu einer deutlichen Einschränkung der Lebensqualität der betroffenen Patientin, nicht zuletzt durch die resultierende Infertilität führen. Andererseits haben verschiedene Studien zeigen können, dass der CIA eine positive prognostische Bedeutung zukommen könnte. Daher kommt der Identifikation von Maßnahmen zur Vermeidung einer CIA (beispielsweise durch den Einsatz von GnRH-Analoga) ein besonderer Stellenwert zu.

Key words

chemotherapy-induced amenorrhea - breast cancer - chemotherapy - GnRH analogues

Schlüsselwörter

chemotherapieinduzierte Amenorrhö - Mammakarzinom - Chemotherapie - GnRH-Analoga

Supporting Information

 

  • References

  • 1 Hankey BF, Miller B, Curtis R et al. Trends in breast cancer in younger women in contrast to older women. J Natl Cancer Inst Monogr 1994; 36: 7-14
    PubMedSearch in Google Scholar
  • 2 Higgins S, Haffty BG. Pregnancy and lactation after breast-conserving therapy for early stage breast cancer. Cancer 1994; 73: 2175-2180
    CrossrefPubMedSearch in Google Scholar
  • 3 Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14: 1718-1729
    PubMedSearch in Google Scholar
  • 4 Kümmel S, Kolberg HC, Lüftner D et al. Mammakarzinom 2011 – Neue Aspekte. Geburtsh Frauenheilk 2011; 71: 939-953
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Hartkopf AD, Banys M, Krawczyk N et al. Circulating tumor cells in early-stage breast cancer. Geburtsh Frauenheilk 2011; 71: 1067-1072
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Böhm J, Zikán M. Einfluss der prognostischen Faktoren auf die Therapie des duktalen Carcinoma in situ der Brust. Geburtsh Frauenheilk 2011; 71: 967-972
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Gerber B, Müller H, Reimer T. Fertilitätserhaltung und Ovarprotektion bei Tumorerkrankungen: Bereits ein Standard?. Geburtsh Frauenheilk 67: 620-627
    Thieme ConnectPubMed
  • 8 Thewes B, Meiser B, Taylor A et al. Fertility- and menopause-related information needs of younger women with a diagnosis of early breast cancer. J Clin Oncol 2005; 23: 5155-5165
    Search in Google Scholar
  • 9 Colleoni M, Rotmensz N, Robertson C et al. Very young women (< 35 years) with operable breast cancer: features of disease at presentation. Ann Oncol 2002; 13: 273-279
    PubMedSearch in Google Scholar
  • 10 Oktay K, Buyuk E, Libertella N et al. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005; 23: 4347-4353
    CrossrefPubMedSearch in Google Scholar
  • 11 Bruning PF, Pit MJ, de Jong-Bakker M et al. Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer 1990; 61: 308-310
    CrossrefPubMedSearch in Google Scholar
  • 12 Jeanes H, Newby D, Gray GA. Cardiovascular risk in women: the impact of hormone replacement therapy and prospects for new therapeutic approaches. Expert Opin Pharmacother 2007; 8: 279-288
    CrossrefPubMedSearch in Google Scholar
  • 13 Zemlin C, Herrmann-Lingen C, Wiegard K et al. Implementierung eines EDV- und Screening-gestützten psychoonkologischen Versorgungspfads. Geburtsh Frauenheilk 2011; 71: 853-861
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Carter J, Rowland K, Chi D et al. Gynecologic cancer treatment and the impact of cancer-related infertility. Gynecol Oncol 2005; 97: 90-95
    CrossrefPubMedSearch in Google Scholar
  • 15 De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet 2010; 376: 911-921
    CrossrefPubMedSearch in Google Scholar
  • 16 Knauff EA, Eijkemans MJ, Lambalk CB et al. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab 2009; 94: 786-792
    CrossrefPubMedSearch in Google Scholar
  • 17 Longway M, Matthews CA. Resumption of ovarian function 20 years after chemotherapy-induced ovarian failure: a case report. Fertil Steril 2009; 92: 392.e17-392.e18
    PubMedSearch in Google Scholar
  • 18 Del Mastro L, Venturini M, Sertoli MR et al. Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications. Breast Cancer Res Treat 1997; 43: 183-190
    CrossrefPubMedSearch in Google Scholar
  • 19 Okanami Y, Ito Y, Watanabe C et al. Incidence of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer following adjuvant anthracycline and taxane. Breast Cancer 2011; 18: 182-188
    CrossrefPubMedSearch in Google Scholar
  • 20 Swain SM, Land SR, Ritter MW et al. Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial. Breast Cancer Res Treat 2009; 113: 315-320
    CrossrefPubMedSearch in Google Scholar
  • 21 Abusief ME, Missmer SA, Ginsburg ES et al. Relationship between reproductive history, anthropometrics, lifestyle factors, and the likelihood of persistent chemotherapy-related amenorrhea in women with premenopausal breast cancer. Fertil Steril 2012; 97: 154-159
    CrossrefPubMedSearch in Google Scholar
  • 22 Dann EJ, Epelbaum R, Avivi I et al. Fertility and ovarian function are preserved in women treated with an intensified regimen of cyclophosphamide, adriamycin, vincristine and prednisone (Mega-CHOP) for non-Hodgkin lymphoma. Hum Reprod 2005; 20: 2247-2249
    CrossrefPubMedSearch in Google Scholar
  • 23 Di Cosimo S, Alimonti A, Ferretti G et al. Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer. Ann Oncol 2004; 15: 1065-1071
    CrossrefPubMedSearch in Google Scholar
  • 24 Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 2006; 24: 5769-5779
    CrossrefPubMedSearch in Google Scholar
  • 25 Stearns V, Schneider B, Henry NL et al. Breast cancer treatment and ovarian failure: risk factors and emerging genetic determinants. Nat Rev Cancer 2006; 6: 886-893
    CrossrefPubMedSearch in Google Scholar
  • 26 Mertens AC, Yasui Y, Neglia JP et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J Clin Oncol 2001; 19: 3163-3172
    PubMedSearch in Google Scholar
  • 27 Partridge AH, Ruddy KJ. Fertility and adjuvant treatment in young women with breast cancer. Breast 2007; 16 (Suppl. 02) S175-S181
    CrossrefPubMedSearch in Google Scholar
  • 28 Tham YL, Sexton K, Weiss H et al. The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am J Clin Oncol 2007; 30: 126-132
    CrossrefPubMedSearch in Google Scholar
  • 29 Han HS, Ro J, Lee KS et al. Analysis of chemotherapy-induced amenorrhea rates by three different anthracycline and taxane containing regimens for early breast cancer. Breast Cancer Res Treat 2009; 115: 335-342
    CrossrefPubMedSearch in Google Scholar
  • 30 Colleoni M, Gelber S, Goldhirsch A et al. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol 2006; 24: 1332-1341
    CrossrefPubMedSearch in Google Scholar
  • 31 Abusief ME, Missmer SA, Ginsburg ES et al. The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer 2010; 116: 791-798
    CrossrefPubMedSearch in Google Scholar
  • 32 Rose DP, Davis TE. Effects of adjuvant chemohormonal therapy on the ovarian and adrenal function of breast cancer patients. Cancer Res 1980; 40: 4043-4047
    PubMedSearch in Google Scholar
  • 33 Warne GL, Fairley KF, Hobbs JB et al. Cyclophosphamide-induced ovarian failure. N Engl J Med 1973; 289: 1159-1162
    CrossrefPubMedSearch in Google Scholar
  • 34 Weenen C, Laven JS, Von Bergh AR et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10: 77-83
    CrossrefPubMedSearch in Google Scholar
  • 35 La Marca A, Broekmans FJ, Volpe A et al. Anti-Mullerian hormone (AMH): what do we still need to know?. Hum Reprod 2009; 24: 2264-2275
    CrossrefPubMedSearch in Google Scholar
  • 36 Dittrich R, Maltaris T, Hoffmann I et al. Fertility preservation in cancer patients. Minerva Ginecol 2010; 62: 63-80
    PubMedSearch in Google Scholar
  • 37 Rossi E, Morabito A, Di Rella F et al. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol 2009; 27: 3192-3197
    CrossrefPubMedSearch in Google Scholar
  • 38 Anderson RA, Themmen AP, Al-Qahtani A et al. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 2006; 21: 2583-2592
    CrossrefPubMedSearch in Google Scholar
  • 39 Anders C, Marcom PK, Peterson B et al. A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer. Cancer Invest 2008; 26: 286-295
    CrossrefPubMedSearch in Google Scholar
  • 40 Su HI, Sammel MD, Green J et al. Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors. Cancer 2010; 116: 592-599
    CrossrefPubMedSearch in Google Scholar
  • 41 Anderson RA, Cameron DA. Pretreatment serum anti-mullerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J Clin Endocrinol Metab 2011; 96: 1336-1343
    CrossrefPubMedSearch in Google Scholar
  • 42 Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy. Oncologist 2006; 11: 422-434
    PubMedSearch in Google Scholar
  • 43 Chen H, Li J, Cui T et al. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011; (11) CD008018
    PubMedSearch in Google Scholar
  • 44 Bedaiwy MA, Abou-Setta AM, Desai N et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril 2011; 95: 906-14.e1-906-14.e4
    PubMedSearch in Google Scholar
  • 45 Munster PN, Moore AP, Ismail-Khan R et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. J Clin Oncol 2012; 30: 533-538
    CrossrefPubMedSearch in Google Scholar
  • 46 Gerber B, von Minckwitz G, Stehle H et al. Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J Clin Oncol 2011; 29: 2334-2341
    CrossrefPubMedSearch in Google Scholar
  • 47 Blumenfeld Z. ZORO study: discrepancy between the conclusion and the results. J Clin Oncol 2011; 29: 3340 author reply 3341–3342
    CrossrefPubMedSearch in Google Scholar
  • 48 Lawrenz B, Neunhoeffer E, Wallwiener D et al. Management des Fertilitätserhaltes bei Mammakarzinom-Patientinnen unter 40 Jahren an der Universitätsfrauenklinik Tübingen. Geburtsh Frauenheilk 2007; 96: A066
    PubMedSearch in Google Scholar
  • 49 von Wolff M, Montag M, Dittrich R et al. Fertility preservation in women–a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkinʼs lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT. Arch Gynecol Obstet 2011; 284: 427-435
    CrossrefPubMedSearch in Google Scholar
  • 50 Cruz MR, Prestes JC, Gimenes DL et al. Fertility preservation in women with breast cancer undergoing adjuvant chemotherapy: a systematic review. Fertil Steril 2010; 94: 138-143
    CrossrefPubMedSearch in Google Scholar
  • 51 Jung M, Shin HJ, Rha SY et al. The clinical outcome of chemotherapy-induced amenorrhea in premenopausal young patients with breast cancer with long-term follow-up. Ann Surg Oncol 2010; 17: 3259-3268
    CrossrefPubMedSearch in Google Scholar
  • 52 Swain SM, Jeong JH, Geyer Jr. CE et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010; 362: 2053-2065
    CrossrefPubMedSearch in Google Scholar
  • 53 Parulekar WR, Day AG, Ottaway JA et al. Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study – NCIC CTG MA.5. J Clin Oncol 2005; 23: 6002-6008
    CrossrefPubMedSearch in Google Scholar
  • 54 Park IH, Han HS, Lee H et al. Resumption or persistence of menstruation after cytotoxic chemotherapy is a prognostic factor for poor disease-free survival in premenopausal patients with early breast cancer. Ann Oncol 2012; 23: 2283-2289
    CrossrefPubMedSearch in Google Scholar
  • 55 Kupka MS, Dittrich R, Nawroth F et al. Fertility protection for women. Techniques, indications and perspectives. Gynnäkologische Endokrinologie 2012; 10: 98-104
    PubMedSearch in Google Scholar