Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: Systematic review and meta-analysis of randomized trials

Background: The role of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) in the prevention of chemotherapy-induced premature ovarian failure (POP) is still controversial. We conducted a systematic review and meta-analysis of randomized trials evaluating the efficacy of GnRHa, given before and during chemotherapy, in the prevention of POF in premenopausal cancer patients. Methods: Studies were retrieved by searching PubMed, Web of Knowledge database and the proceedings of major conferences. We calculated Odds Ratios (OR) and 95% confidence intervals (CIs) for POF from each trial and obtained pooled estimates through the random effects model as suggested by DerSimonian and Laird. Results: Nine studies were included in the meta-analysis with 225 events of POF occurring in 765 analyzed patients. The pooled OR estimate indicates a highly significant reduction in the risk of POF (OR= 0.43; 95% Cl: 0.22-0.84; p = 0.013) in patients receiving GnRHa. There was statistically significant heterogeneity among studies (I-2 = 55.8%; p = 0.012). There was no evidence of publication bias. Subgroups analyses showed that the protective effect of GnRHa against POF was similar in subgroups of patients defined by age and timing of POF assessment, while it was present in breast cancer but unclear in ovarian cancer and lymphoma patients. Conclusions: Our pooled analysis of randomized studies shows that the temporary ovarian suppression induced by GnRHa significantly reduces the risk of chemotherapy-induced POF in young cancer patients. (C) 2013 Elsevier Ltd. All rights reserved.