title: Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials.
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.
authors.affiliation: 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.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.affiliation: UO Clinical Epidemiology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: marcello.ceppi@hsanmartino.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceppi
authors.affiliation: Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: francesca.poggio.1987@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Poggio
authors.affiliation: Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: claudia.bighin@hsanmartino.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bighin
authors.affiliation: Fertility and Reproduction Unit, Department of Medicine, European Institute of Oncology, Milano, Italy. Electronic address: fedro.peccatori@ieo.it.
authors.forename: Fedro
authors.initials: F
authors.lastname: Peccatori
authors.affiliation: Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: idemeest@ulb.ac.be.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Demeestere
authors.affiliation: 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.
authors.forename: Alessia
authors.initials: A
authors.lastname: Levaggi
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Giraudi
authors.affiliation: Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: matteo.lambertini@hsanmartino.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: 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.
authors.forename: Alessia
authors.initials: A
authors.lastname: D'Alonzo
authors.affiliation: Breast Surgery Unit, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: giuseppe.canavese@hsanmartino.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Canavese
authors.affiliation: Medical Oncology A, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: paolo.pronzato@hsanmartino.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
authors.affiliation: UO Clinical Epidemiology, IRCCS AOU San Martino-IST, National Institute for Cancer Research, Genova, Italy. Electronic address: paolo.bruzzi@hsanmartino.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D061214:Patient Safety; D017697:Premenopause / Q000187:drug effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000517:prevention & control*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007987:Gonadotropin-Releasing Hormone; C083781:LHRH, Ala(6)-Gly(10)-ethylamide-
keywords: Breast cancer; Chemotherapy-induced ovarian failure; Fertility preservation; GnRH analogues; Lymphoma; Meta-analysis