title: Association between growth hormone therapy and mortality, cancer and cardiovascular risk: systematic review and meta-analysis.
abstract: OBJECTIVE
  The potential involvement of growth hormone therapy in tumor promotion and progression has been of concern for several decades. Our aim was to assess systematically the association between growth hormone therapy and all-cause, cancer and cardiovascular mortality, cancer morbidity and risk of second neoplasm mainly in patients treated during childhood and adolescence.
  
  
  METHODS
  A systematic review of all articles published until September 2013 was carried out. The primary efficacy outcome measures were the all-cause, cancer and cardiovascular standardized mortality ratios (SMR). The secondary efficacy outcome measures were the standardized incidence ratio (SIR) for cancer and the relative risk (RR) for second neoplasms. The global effect size was calculated by pooling the data. When the effect size was significant in a fixed model we repeated the analyses using a random model.
  
  
  RESULTS
  The overall all-cause SMR was 1.19 (95% CI 1.08-1.32, p<0.001). Malignancy and cardiovascular SMRs were not significantly increased. Both the overall cancer SIR 2.74 (95% CI 1.18-5.41), and RR for second neoplasms 1.99 (95% CI 1.28-3.08, p=0.002), were significantly increased.
  
  
  CONCLUSIONS
  The results of this meta-analysis may raise concern on the long-term safety of GH treatment. However, several confounders and biases may affect the analysis. Independent, long-term, well-designed studies are needed to properly address the issue of GH therapy safety.
authors.affiliation: D.P.U.O. "Bambino Gesù" Children's Hospital - "Tor Vergata" University, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Deodati
authors.affiliation: D.P.U.O. "Bambino Gesù" Children's Hospital - "Tor Vergata" University, Rome, Italy.
authors.forename: Barbara Baldini
authors.initials: BB
authors.lastname: Ferroli
authors.affiliation: D.P.U.O. "Bambino Gesù" Children's Hospital - "Tor Vergata" University, Rome, Italy; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. Electronic address: stefano.cianfarani@opbg.net.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cianfarani
mesh_terms: D000293:Adolescent; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality*; D002675:Child, Preschool; D004392:Dwarfism / Q000188:drug therapy; D013006:Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000401:mortality; D012307:Risk Factors
chemical_list: D013006:Growth Hormone
keywords: Growth hormone; Growth hormone therapy; IGF-I; Metaanalysis