title: Reviewing the safety of GH replacement therapy in adults.
abstract: BACKGROUND
  Systematic data on safety of growth hormone (GH) replacement therapy in adult GH deficiency is lacking.
  
  
  OBJECTIVE
  To systematically describe safety of adult GH replacement therapy on glucose metabolism and long term safety.
  
  
  METHODS
  A systematic web-based search of PubMed was performed guided by the Standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
  
  
  RESULTS
  Randomised controlled trials of ≥3 months and open trials for ≥12 months with more than 50 adult patients (50 patient years, prospective and retrospective) including adverse event reporting as well as articles on mortality primarily on adult onset patients, reporting mortality ratios on GH treated patients, were included for the review.
  
  
  RESULTS
  Based on the defined selection criteria 94 studies were included. The short-term early placebo controlled trials did not demonstrate an increased frequency of diabetes mellitus (DM) and the long-term open studies did not consistently show an increased incidence of DM during GH replacement. The concern that long-term GH replacement might increase the risk of primary cancer, secondary neoplasia after tumour treatment and recurrence of previous tumours was not evident in the study data.
  
  
  CONCLUSIONS
  Based on available data, short- and long-term adult GH replacement in patients with severe GH deficiency and hypopituitarism is safe. However, the small number of subjects, limitation of long-term of GH treatment data and absence of an adequate control population is still a limitation for the interpretation of these data.
authors.affiliation: Department of Internal Medicine and Endocrinology, Aarhus University Hospital, 8000, Aarhus C, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Stochholm
authors.affiliation: Department of Endocrinology, Grstr 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden; Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Göteborg, Grstr 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D003920:Diabetes Mellitus / Q000139:chemically induced*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D019382:Human Growth Hormone / Q000009:adverse effects* / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy*; D009026:Mortality; D009369:Neoplasms / Q000139:chemically induced*; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone
keywords: Adults; Growth hormone; Hypopituitarism; Morbidity; Mortality; Safety