Reviewing the safety of GH replacement therapy in adults

Systematic data on safety of growth hormone (GH) replacement therapy in adult GH deficiency is lacking.

To systematically describe safety of adult GH replacement therapy on glucose metabolism and long term safety.

A systematic web-based search of PubMed was performed guided by the Standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

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.

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.

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.