Comment on the Symposiumarticle “Fertility after treatmentfor Hodgkin’s disease”, byZ. Blumenfeld, E. Dann, I. Aviviet al. (Ann Oncol 2002; 13 Suppl 1:138–147)
Authors: M.K. Bohlmann, M. von Wolff, T. Strowitzki
Journal: Annals of Oncology (2003)

We read with interest the article by Blumenfeld et al. concerning the gonadotropin-releasing hormone agonistic analogue (GnRH-a) co-treatment in women of reproductive age receiving gonadotoxic chemotherapy for diseases such as leukaemia, lymphoma and systemic lupus erythematosus, or other autoimmune diseases[1.Blumenfeld Z. Dann E. Avivi I. et al.Fertility after treatment for Hodgkin’s disease.Ann Oncol. 2002; 13: 138-147Abstract Full Text PDF PubMed Scopus (146) Google Scholar]. Blumenfeld et al. should be congratulated for their skilful presentation of today’s alternatives for fertility preservation, particularly, showing a significantly lower rate (3/58) of premature ovarian failure in patients with the combined GnRH-a and chemotherapy compared with those who were similarly treated with chemotherapy, but without GnRH-a adjuvant (32/58). However, a few questions have to be put forward. First, neither the exact time of follow-up nor the patients’ outcome is mentioned for either group. As the “dosages of the various cytotoxic drugs were not significantly different between both groups”, it would be of interest to know whether there was any difference with regard to the patients’ disease-free survival, especially since “several” (how many? when?) patients in the control group suffered from recurrence of the disease. Were those with recurrent disease undergoing high-dose chemotherapy and autologous bone marrow transplantation not co-treated with GnRH-a? Furthermore, Blumenfeld et al. focused primarily on theeffect of the GnRH analogues on the ovaries. However, it is well established that tumour cell lines, both gynaecological [2.Palyi I. Vincze B. Lovas S. et al.Gonadotropin-releasing hormone analogue conjugates with strong selective antitumor activity.Proc Natl Acad Sci USA. 1999; 96: 2361-2366Crossref PubMed Scopus (40) Google Scholar] and non-gynaecological (e.g. pancreatic cancer cells [3.Huang W. Yao B. Sun L. et al.Immunohistochemical and in situ hybridization studies of gonadotropin releasing hormone (GnRH) and its receptor in rat digestive tract.Life Sci. 2001; 68: 1727-1734Crossref PubMed Scopus (75) Google Scholar]), may carry receptors for GnRH. Results from in vitro experiments suggest that GnRH analogues may modulate cancer cell growth [2.Palyi I. Vincze B. Lovas S. et al.Gonadotropin-releasing hormone analogue conjugates with strong selective antitumor activity.Proc Natl Acad Sci USA. 1999; 96: 2361-2366Crossref PubMed Scopus (40) Google Scholar], possibly by interfering with the stimulatory effect of growth factors (such as epidermal growth factor [4.Pagnini U. Florio S. Crispino L. et al.Direct effect of a gonadotropin-releasing hormone agonist on the growth of canine mammary tumour cells.J Cell Biochem. 2002; 85: 470-481Crossref Scopus (11) Google Scholar]) and enhance the cytotoxic effects of chemotherapy [5.Ohta H. Sakamoto H. Satoh K. In vitro effects of gonadotropin-releasing hormone (GnRH) analogue on cancer cell sensitivity to cis-platinum.Cancer Lett. 1998; 134: 111-118Crossref PubMed Scopus (22) Google Scholar]. It would therefore be of interest whether such results, with hypothetical beneficial effects, might also be obtained from experiments with lymphoma or leukaemia cells. However, to our knowledge, no experimental data are available on the interaction of GnRH-a and lymphoma or leukaemia cells. In our opinion, such hypothetical effects should therefore be studied in detail before considering a combined GnRH-a and chemotherapy regimen for diseases such as leukaemia, lymphoma and systemic lupus erythematosus “in every woman of reproductive age”. In addition, the patients’ age range in the Abstract (15–40 years) and in Table 1 (14–40 years) do not match. Michael K. Bohlmann was supported by a grant from the Medical Faculty, University of Heidelberg, Germany.