Gonadotrophin Releasing Hormone Analogues for Ovarian Function Preservation in Young Females Undergoing Chemotherapy

  • Published : 2014.03.01


Chemotherapy has significantly improved the prognosis of cancer patients with various malignancies. However, female patients, especially those whoich are premenopausal, suffer from significant chemotherapy induced ovarian function impairment, which decreases their quality of life. Many new techniques for ovarian preservation have been established in recent years. Although the use of gonadotrophin releasing hormone analogues (GnRHa) for this purpose is not a new concept, its effectiveness in protection of ovarian function is still debatable. This article deals with studies and metaanalyses which have been undertaken in the past, demonstrating the impact of GnRHa in ovarian function preservation, and whether their use can be implemented in routine practice.


  1. Ortin TT, Shostak CA, Donaldson SS (1990). Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: the Stanford experience. Int J Radiat Oncol Biol Phys, 19, 873-80.
  2. Walshe J, Denduluri N, Swain S (2006). Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol, 24, 5769-79.
  3. Licciardi FL, Liu HC, Rosenwaks Z (1995). Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril, 64, 991-4.
  4. Maltaris T, Seufert R, Fischl F et al (2007) The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur J Obstet Gynecol Reprod Biol, 130, 148-55.
  5. Oktay K, Briggs D, Gosden RG (1997). Ontogeny of folliclestimulating hormone receptor gene expression in isolated human ovarian follicles. J Clin Endocrinol Metab, 82, 3748-51.
  6. Oktay K, Sonmezer M, Oktem O et al (2007). Absence of Conclusive Evidence for the Safety and Efficacy of gonadotropin-releasing hormone analogue treatment in protecting against chemotherapy-induced gonadal injury. Oncologist, 12, 1055-66
  7. Osborne SE, Detti L (2013). GnRH-analogues for ovarian protection in childhood cancer patients: how adult hypotheses are relevant in prepubertal females. Curr Drug Targets, 14, 856-63.
  8. Rahilly M, Carder PJ, Nafussi A et al (1991). Distribution of glutathione Stransferase isoenzymes in human ovary. J Reprod Fertil, 93, 303-11.
  9. Scott RT, Toner JP, Muasher SJ et al (1989). Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome. Fertil Steril, 51, 651-4.
  10. Shalev E, Leung PC (2003). Gonadotropin-releasing hormone and reproductive medicine. J Obstet Gynaecol Can, 25, 98-113.
  11. Fox K, Scialla H, Moore H (2001). Preventing chemotherapyrelated amenorrhea using leuprolide during adjuvant chemotherapy for early stage breast cancer. Proc Am Soc Clin Oncol, 21, 98.
  12. Del Mastro L, Catzeddu T, Boni L et al (2006). Prevention of chemotherapy induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients. Ann Oncol, 17, 74-8.
  13. Del Mastro L, Ceppi M, Poggio F(2013). Gonadotropin-releasing hormone analogues for the prevention of chemotherapyinduced premature ovarian failure in cancer women: Systematic review and meta-analysis of randomized trials. Cancer treatment reviews. Cancer Treat Rev, [Epub ahead of print]
  14. Emons G, Grundker C, Gunthert AR et al (2003). GnRH antagonists in the treatment of gynaecological and breast cancers. Endocr Relat Cancer, 10, 291-9.
  15. Huser M, Zakova J, Smardova L et al (2012). Combination of fertility preservation strategies in young women with recently diagnosed cancer. Eur J Gynaecol Oncol, 33, 42-50.
  16. Kreuser ED, Hetzel WD, Billia DO, Thiel E (1990). Gonadal toxicity following cancer therapy in adults: significance, diagnosis, prevention and treatment. Cancer Treat Rev, 17, 169-75.
  17. Lamar CA, DeCherney AH (2009). Fertility preservation: state of the science and future research directions. Fertil Steril, 91, 316-9.
  18. Laml T, Schulz-Lobmeyr I, Obruca A, Huber J, Hartmann B (2000).Premature ovarian failure: Etiology and prospects. Gynecol Endocrinol, 14, 292-302.
  19. Lee SJ, Schover LR , Partridge AH et al (2006). American Society of Clinical Oncology. Recommendations on Fertility Preservation in Cancer Patients. J Clin Oncol, 24, 2917-31
  20. Bonadonna G, Valagussa P (1985). Adjuvant systemic therapy for resectable breast cancer. J Clin Oncol, 3, 259-75.
  21. Ataya K, Ramahi-Ataya A (1993). Reproductive performance of female rats treated with cyclophosphamide and/or LHRH agonist. Reprod Toxicol, 7, 229-35.
  22. Balkenende E, Dahhan T, Veen F, Goddijn M (2011). Comment on GnRH analogue cotreatment with chemotherapy for preservation of ovarian function. Fertil Steril, 96, 155-6
  23. Bedaiwy MA, Abou-Setta AM, Desai N et al (2011). Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril, 95, 906-14
  24. Chen H, Li J, Cui T, Hu L (2011). Adjuvant gonadotropinreleasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev, 11, 8018.
  25. Clowse MEB, Behera MA, Anders CK et al (2009). Ovarian preservation by GnRH agonists during chemotherapy: A Meta-Analysis. J Wom Health, 18, 311-9.
  26. Cobleigh M (1995). Amenorrhea following adjuvant chemotherapy for breast cancer. Proc Am Soc Clin Oncol, 14, 158.
  27. Dada T, Salha O, Allgar V, Sharma V (2001). Utero-ovarian blood flow characteristics of pituitary desensitization. Hum Reprod, 16, 1663-70.