Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency

Objective: GH deficiency is associated with an increased cardiovascular mortality. Fifty-live patients with adult-onset GH deficiency (AO-GRD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-con trolled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis. including apolipoproteins (Apo A-1 Apo B). markers of subclinical inflammation (high-sensitivity C-reactive protein (CRP) and interleukin-6) and markers of endothelial function (intercellular adhesion molecule-1. von Willebrand factor and sCD40L (a pro-atherogenic factor and marker for plaque destabilization)). Methods: GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each. separated by a 4 month washout period. Results: The final mean dose of GH was 50% higher for women and IGF-I increased to the same level in both sexes. Compared with placebo, substitution with GH showed a significant effect on Apo B (mean change - 0.15 (-0.22 to -0.08) mg/l) and CRP (- 1.8 (- 3.3 to -0.3) mg/l). The baseline level of and change in IGF-I during treatment with GH contributed significantly to the improvement in both markers. No effects were found on interleukin-6 or Apo A-1, or oil markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention. Conclusions: GH Substitution to naive patients with AO-GHD at a low, individually titrated dose aiming at normalizing IGF-I was followed by significant reductions in Apo B and CRP. indicating a positive effect of GH on cardiovascular risk.