title: Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Premature ovarian failure and infertility following chemotherapy are major concerns for premenopausal women with breast cancer. A potential ovarian function preservation strategy is administration of gonadotropin-releasing hormone (GnRH) agonists during adjuvant chemotherapy; however, studies of the clinical efficacy of GnRH agonists to protect chemotherapy-induced ovarian damage have shown mixed results.
  
  
  OBJECTIVE
  This meta-analysis study was designed to estimate the efficacy of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian damage in premenopausal women with breast cancer.
  
  
  METHODS
  Electronic literature databases (PubMed, EMBASE, MEDLINE, Cochrane Library databases searching, China National Knowledge Infrastructure, Web of Science, and the Wanfang Data) were searched for relevant randomized controlled trials (RCTs) published until September 2015. Only RCTs that examined the effect of GnRH agonists for chemotherapy-induced ovarian failure in premenopausal women with breast cancer were selected. The rate of spontaneous resumption of menses and spontaneous pregnancy were collected. All data were analyzed by RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) and Stata 12.0 (StataCorp, College Station, TX, USA).
  
  
  RESULTS
  Eleven RCTs with a total of 1,062 participants (GnRH agonists administered concurrently with chemotherapy, n=541; chemotherapy alone, n=521) were included in the meta-analysis. A significantly greater number of women treated with GnRH agonist experienced spontaneous resumption of menses after the adjuvant chemotherapy, yielding a pooled odds ratio of 2.57 (versus chemotherapy alone, 95% confidence interval (CI)=1.65, 4.01; P<0.0001). A subgroup analysis showed that addition of GnRH agonists significantly improved the resumption of menses rate in patients who were hormone-insensitive. However, the two treatment groups experienced similar spontaneous pregnancy (odds ratio =0.177; 95% CI=0.92, 1.40; P=0.09).
  
  
  CONCLUSIONS
  GnRH agonists cotreatment with chemotherapy in premenopausal women with breast cancer plays a beneficial role in resumption of ovarian function, with a higher rate of resumption of menses. However, treatment with GnRH agonists does not appear to exhibit its protective effects in fertility.
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Tian-Jie
authors.initials: TJ
authors.lastname: Qin
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Pei-Jun
authors.initials: PJ
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
keywords: GnRH agonists; breast cancer; chemotherapy; meta-analysis; ovarian damage