Systemic Effects of Growth Hormone in Growth Hormone Deficient Adults: A Meta-Analysis of 48 Prospective Studies

Abstract

Introduction: The use of growth hormone (GH) treatment in GH deficiency (GHD) continues to increase. However, individual controlled trials of the efficacy and safety of GH have involved relatively few patients and yielded variable results. We seek to analyze the overall effect of GH treatment on various parameters by performing a contemporary meta-analysis of the efficacy and safety of GH administration. Methods: Meta-analysis of 48 blinded, placebo controlled, randomized clinical studies of GH treatment in GHD adults published up to June 2011 was performed. Analyzed variables included anthropomorphic measurements (waist-hip ratio (WHR), lean body mass (LBM)/fat free mass (FFM), trunk fat (TrF), total body water (TBW), fat mass (FM), and body mass index (BMI)); cardiovascular (CV) parameters (systolic/diastolic blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), LDL, HDL, total cholesterol (TChol), triglycerides (TG), apolipoprotein B (ApoB), C-reactive protein (CRP)); and diabetes parameters (fasting insulin and glucose, hemoglobin A1c (HgbA1c)). Effect sizes (ES) were used to determine significance and weighted mean differences between GH and control were used to quantify size of effect. Results: 2231 adults with growth hormone deficiency were included. Significant beneficial changes resulting from GH administration were observed in the following variables: anthropomorphic—WHR, FM, LBM, FFM, TBW; cardiovascular—LDL, HDL, TChol, ApoB, CRP; significant adverse changes were seen in diabetic parameters—fasting insulin, fasting glucose, and HgbA1c. Compared to prior meta-analyses, larger ESs were observed for LDL, HDL, total cholesterol, fasting insulin and fasting glucose levels. Conclusions: GH administration in GHD adults results in improvement in anthropomorphic parameters, as well as CV parameters, but with worsening of diabetes markers. Data on long-term safety, including on CV effects and malignancy, as well as data assessing the role of GH replacement in combination with testosterone replacement continue to be sparse.