Association between growth hormone therapy and mortality, cancer and cardiovascular risk: Systematic review and meta-analysis

ObjectiveThe 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.DesignA 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.ResultsThe 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.ConclusionThe 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.