Possible applications analogues of gonadotropin-releasing hormone puberty in girls with cancer

Recent diagnostic and therapeutic advances in pediatric oncology have led to increased survival rates in children with malignancies. Today many investigations are devoted to the adverse effects during and after anticancer treatment, possible methods of their prevention and control. Menorrhagia is a serious complication in post-pubertal females who suffer from thrombocytopenia during myelosuppressive treatment. The issues of the effective prevention of this complication is highly discussed and a great interest is devoted to Gonadotropin-releasing hormone (GnRH) analogues. This option was not chosen by chance: the perspective method of prevention ovarian function is hormonal gonadoprotection. There are no definite data about the effectiveness of GnRH analogs yet, and it remains controversial. In this issue we’d like to summarize international data and our experience of the use of GnRH agonists in adolescents during chemotherapy.

analogues of gonadotropin-releasing hormone, adolescents, pediatric oncology, menorrhagia, fertility, chemotherapy, mielosuprescia, reproduction, gonadal toxicity, hormonotherapy

1. Brenner H., Coebergh J.W., Parkin D.M. et al. Up-to-date monitoring of childhood cancer long-term survival in Europe: Leukaemias and lymphomas. Ann Oncol 2007;18(9):1569–77.

2. Blumenfeld Z., von Wolff M. GnRHanalogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum Reprod Update 2008;14(6):543–52.

3. Michaeli J., Weintraub M., Gross E. et al. Fertility preservation in girls. Obstet Gynecol Int 2012;2012:139193.

4. Del Mastro L., Ceppi M., Poggio F. et al. Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: Systematic review and meta-analysis of randomized trials. Cancer Treat Rev 2014;40(5):675–83.

5. Белогурова М.Б. Диникина Ю.В., Тапильская Н.И. и др. Нарушение фертильности как осложнение лечения онкологических заболеваний в детском и подростковом возрасте (обзор литературы). Евразийский онкологический журнал 2014;1:77–86. [Belogurova М.B., Dinikina Yu.V., Tapilskaya N.I. Violation of fertility as a complication of cancer treatment in children and adolescents (review). Yevraziyskiy onkologicheskiy zhurnal = Eurasian Journal of Oncology 2014;1:77–86. (In Russ.)].

6. Brown J., Demetri G. Challenges in the development of platelet growth factors: low expectations for low counts. Curr Hematol Rep 2002;1(2):110–8.

7. Meirow D., Rabinovici J., Katz D. et al. Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormonereleasing hormone agonist and depomedroxyprogesterone acetate. Cancer 2006;107(7):1634–41.

8. Committee opinion no. 606: Options for prevention and management of heavy menstrual bleeding in adolescent patients undergoing cancer treatment. Obstet Gynecol 2014;124(2 Pt 1):397–402.

9. Hanker J.P. Gastrointestinal disease and oral contraception. Am J Obstet Gynecol 1990;163(6 Pt 2):2204–7.

10. Bates J.S., Buie L.W., Woodis C.B. Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy. Pharmacotherapy 2011;31(11):1092–110.

11. Kline R., Fennewald L., Vore M. et al. Oral contraceptives a cause of hyperbilirubinemia in stem cell transplant patients. J Pediatr Hematol Oncol 1999;21(5):436–40.

12. Quaas A.M., Ginsburg E.S. Prevention and treatment of uterine bleeding in hematologic malignancy. Eur J Obstet Gynecol Reprod Biol 2007;134(1):3–8.

13. Loren A.S., Mangu P.B., Beck L.N. et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31(19):2500–10.

14. Patridge A.H., Gelber S., Peppercorn J. et al. Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol 2004;22(20):4174–83.

15. Диникина Ю.В. Оптимизация методов сохранения фертильности у девочек с онкологической патологией. Диссертация на соискание ученой степени к.м.н. СПб.: [б.н.], 2011. 145 с. [Dinikina Yu.V. Optimization methods of fertility preservation for girls with cancer pathology. Dissertation for the degree of Ph.D. SPb.: [unnumbered], 2011. 145 p. (In Russ.)].

16. Peccatori F.A., Azim H.A. Jr, Orrecchia R. et al.; ESMO Guidelines Working Group. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24 Suppl 6:vi160–70.

17. Sklar C.A., Mertens A.C., Mitby P. et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2006;98(13):890–6.

18. Ortin T., Shostak C., Donaldson S. Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: the Stanford experience. Int J Radiat Oncol Biol Phys 1990;19(4):873–80.

19. Beck-Fruchter R., Weiss A., Shalev E. GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data. Hum Reprod Update 2008;14(6):553–61.

20. Demeestere I., Brice P., Peccatori F. et al. Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced ovarian failure in patients with lymphoma: 1-year follow-up of a prospective randomized trial. J Clin Oncol 2013;31(7):903–9.

21. Blumenfeld Z. How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embrya, oocytes, or ovaries. Oncologist 2007;12(9):1044–54.

22. Clowse M.E., Behera M.A., Anders C.K. et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt) 2009;18(3):311–9.

23. Chen H., Li J., Cui T., Hu L. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011;(11):CD008018.

24. Slater C.A., Liang M.H., McCune J.W. et al. Preserving ovarian function in patients receiving cyclophosphamide. Lupus 1999;8(1):3–10.

25. Ataya M., McKanna J., Weintraub A. et al. A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Res 1985;45(8):3651–6.

26. Bokser L., Szende B., Schally A. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats. Br J Cancer 1990;61(6):861–5.

27. Ataya K., Ramahi-Ataya A. Reproductive performance of female rats treated with cyclophosphamide and/or LHRH agonist. Reprod Toxicol 1993;7(3):229–35.

28. Ataya K., Rao L.V., Lawrence E., Kimmel R. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamideinduced ovarian follicular depletion in rhesus monkeys. Biol Reprod 1995;52(2):365–72.

29. Imai A., Sugiyama M., Furui T. et al. Direct protection by gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage. Gynecol Obstet Invest 2007;63(2):102–6.

30. Letterie G.S. Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure. Hum Reprod 2004;19(4):831–7.

31. Blumenfeld Z. Gender difference: fertility preservation in young women but not in men exposed to gonadotoxic chemotherapy. Minerva Endocrinol 2007;32(1):23–34.

32. Lobo R.A. Potential options for preservation fertility in women. N Engl J Med 2005;353(1):64–73.

33. Oktay K., Sönmezer M., Oktem O. et al. Absence of conclusive evidence for the safety and efficacy of gonadotropin-releasing hormone analogue treatment in protecting against chemotherapy-induced gonadal injury. Oncologist 2007;12(9):1055–66.

34. Sönmezer M., Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004;10(3):251–66.

35. Kitajima Y., Endo T., Nagasawa K. et al. Hyperstimulation and a gonadotropinreleasing

36. hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5. Endocrinology 2006;147(2):694–9.

37. Yu N., Chan C., Tang O. et al. Effect of pituitary downregulation on antral follicle count, ovarian volume and stromal blood flow measured by three-dimensional ultrasound with power Doppler prior to ovarian stimulation. Hum Reprod 2004;19(12):2811–5.

38. Blumenfeld Z. Gynecologic concerns for young women exposed to gonadotoxic chemotherapy. Curr Opin Obstet Gynecol 2003;15(5):359–70.

39. Janssens R., Brus L., Cahill D. et al. Direct ovarian effects and safety aspects of GnRH agonists and antagonists. Hum Reprod Update 2000;6(5):505–18.

40. Kolesnick R.N., Krönke M. Regulation of ceramide production and apoptosis. Annu Rev Physiol 1998;60:643–65.

41. Tilly J.L. Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol 2001;2(11):838–48.

42. Johnson J., Canning J., Kaneko T. et al. Germline stem cells and follicular renewal in

43. the postnatal mammalian ovary. Nature 2004;428(6979):145–50.

44. Johansen J., Riis B., Hassager C. et al. The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab 1988;67(4):701–6.

45. Fogelman I. Gonadotropin-releasing hormone agonists and the skeleton. Fertil Steril 1992;57(4):715–24.

46. Scialli A., Jestila K., Simon J. Leuprolide acetate and bone mineral density measured by quantitive radiography. Fertil Steril 1993;59(3):674–6.

47. Qublan H., Amarin Z., Tahat Y. et al. Ovarian cyst formation following Gnrh agonist administration in IVF cycles: incidence and impact. Hum Reprod 2006;21(3):640–4.

48. von Wolff M., Kämmerer U., Kollmann Z. et al. Combination of gonadotropin-releasing hormone (GnRH) agonists with GnRH antagonists before chemotherapy reduce but does not

49. completely prevent a follicle-stimulating hormone flare-up. Fertil Steril 2011;95(1):452–4.

50. Blumenfeld Z., Avivi I., Eckman A. et al. Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma. Fertil Steril 2008;89(1):166–73.

51. Banzal A., Patel F., Rai B. et al. Gonadotrophin releasing hormone analogues for ovarian function preservation in young females undergoing chemotherapy. Asian Pac J Cancer Prev 2014;15(5):2185–90.

52. Somers E.C., Marder W., Christman G.M. et al. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 2005;52(9):2761–7.

53. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril 2012;98(6):1407–15.