In a long-term follow-up of a European trial reported by Isabelle Demeestere, MD, PhD, of the Université Libre de Bruxelles in Belgium, and colleagues in the Journal of Clinical Oncology, gonadotropin-releasing hormone (GnRH) agonist treatment during chemotherapy in young women with lymphoma was not associated with reduced premature ovarian failure or an improved pregnancy rate. A prior report from the study at 1-year follow-up indicated that GnRH agonist treatment did not prevent chemotherapy-induced premature ovarian failure but may have protected ovarian reserve.
In the trial, 129 patients from 15 sites in France, Belgium, and Italy were randomized to receive GnRH agonist treatment with triptorelin (Telstar) plus norethisterone (n = 65) or norethisterone alone (n = 64) during chemotherapy. The primary endpoint was premature ovarian failure, defined as at least one follicle-stimulating hormone (FSH) value of > 40 IU/L after 2 years of follow-up.
A total of 67 patients (mean age = 26.2 years) had available data after median follow-up of 5.33 years in the GnRH agonist group and 5.58 years in the control group. On multivariate analysis, risk of premature ovarian failure was significantly associated with age (P = .047), conditioning regimen for hematopoietic stem cell transplantation (P = .002), and cumulative dose of cyclophosphamide > 5 g/m2 (P = .019) but not with coadministration of GnRH agonist during chemotherapy (odds ratio = 0.702, P = .651). Ovarian reserve evaluated using anti-Müllerian hormone and FSH levels was similar in the two groups. Pregnancy occurred in 53% of patients in the GnRH agonist group and 43% in the control group (P = .467).
The investigators concluded: “To the best of our knowledge, this is the first long-term analysis confirming that GnRH [agonist] is not efficient in preventing chemotherapy-induced premature ovarian failure in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug’s benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.”
The study was supported by the Fonds National de la Recherche Scientifique and Ipsen Pharmaceutical Group.