Lucia Del Mastro1, Marcello Ceppi2, Francesca Poggio3, Claudia Bighin4, Fedro Peccatori5, Isabelle Demeestere6, Alessia Levaggi7, Sara Giraudi8, Matteo Lambertini9, Alessia D'Alonzo10, Giuseppe Canavese11, Paolo Pronzato12, Paolo Bruzzi13. 1. UO Development of Innovative Therapies, Medical Oncology Department, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: lucia.delmastro@hsanmartino.it. 2. UO Clinical Epidemiology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: marcello.ceppi@hsanmartino.it. 3. Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: francesca.poggio.1987@gmail.com. 4. Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: claudia.bighin@hsanmartino.it. 5. Fertility and Reproduction Unit, Department of Medicine, European Institute of Oncology, Milano, Italy. Electronic address: fedro.peccatori@ieo.it. 6. Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: idemeest@ulb.ac.be. 7. UO Development of Innovative Therapies, Medical Oncology Department, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: alessia.levaggi@hsanmartino.it. 8. UO Development of Innovative Therapies, Medical Oncology Department, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: sara.giraudi@hsanmartino.it. 9. Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: matteo.lambertini@hsanmartino.it. 10. UO Development of Innovative Therapies, Medical Oncology Department, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: alessia.dalonzo@hsanmartino.it. 11. Breast Surgery Unit, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: giuseppe.canavese@hsanmartino.it. 12. Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: paolo.pronzato@hsanmartino.it. 13. UO Clinical Epidemiology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: paolo.bruzzi@hsanmartino.it.
Abstract
BACKGROUND: The role of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) 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% CI: 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.
BACKGROUND: The role of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) 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 cancerpatients. 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% CI: 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 lymphomapatients. 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 cancerpatients.
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