title: Growth hormone replacement does not increase mortality in patients with childhood-onset growth hormone deficiency.
abstract: BACKGROUND
  Long-term safety of growth hormone (GH) treatment is an area of much debate. Studies including children treated with GH not only due to GHD, but also due to non-GHD causes like idiopathic short stature or like short stature in children born small for gestational age have suggested that GH treatment is associated with increased mortality or stroke.
  
  
  OBJECTIVE
  To study the impact of GH replacement on overall and cause-specific mortality in childhood-onset GHD (CO GHD) patients.
  
  
  METHODS
  A nationwide population-based registry study on patients with CO GHD and general population controls matched on age and gender. Mortality hazard ratios (HRs) were computed comparing patients and controls, and comparing GH-replaced patients and non-GH-replaced patients, using Cox regression. Comparing GH- and non-GH-replaced patients HRs were adjusted for birth year, year of diagnosis, gender, irradiation, ACTH insufficiency and primary disease.
  
  
  METHODS
  A total of 494 patients with CO GHD each matched with 100 general population controls were included.
  
  
  RESULTS
  Mortality was substantially increased comparing patients with CO GHD and general population controls, HR = 7·51 (95% CI = 6·06-9·31). Comparing GH-replaced patients with non-GH-replaced patients mortality was significantly decreased in total (HR = 0·27, CI = 0·17-0·43) and due to malignancy (HR = 0·14, CI = 0·07-0·28) in GH-replaced patients. Adjusting for relevant confounders, this decrease remained significant both in total (HR = 0·56, CI = 0·32-0·96) and due to malignancy (HR = 0·33, CI = 0·16-0·69). Overall and cause-specific mortality was increased in both GH-replaced and non-GH-replaced patients compared to general population controls, but mortality was generally highest in non-GH-replaced patients.
  
  
  CONCLUSIONS
  The present data from a national cohort of patients with CO GHD do not support the suggestion that GH replacement is associated with increased mortality.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.
authors.forename: Agnethe
authors.initials: A
authors.lastname: Berglund
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.|Department of Molecular Medicine, Aarhus University Hospital, Denmark.
authors.forename: Claus Højbjerg
authors.initials: CH
authors.lastname: Gravholt
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Denmark.
authors.forename: Morten Smaerup
authors.initials: MS
authors.lastname: Olsen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.|Department of Pediatrics, Center of Rare Diseases, Aarhus University Hospital, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Stochholm
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D013006:Growth Hormone / Q000009:adverse effects*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D013006:Growth Hormone