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-five patients with adult-onset GH deficiency (AO-GHD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-controlled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis, including apolipo-proteins (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 on markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention.


CONCLUSIONS
GH substitution to naïve 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.
Section of Endocrinology, The National University Hospital, Oslo, Norway. jens.bollerslev@klinmed.uio.no
Jens
J
Bollerslev
Thor
T
Ueland
Anders P
AP
Jørgensen
Kristian J
KJ
Fougner
Ragnhild
R
Wergeland
Thomas
T
Schreiner
Pia
P
Burman
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors
D001055:Apolipoproteins B; D015415:Biomarkers; D008078:Cholesterol, LDL; D008055:Lipids; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein; D002784:Cholesterol