Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.
BACKGROUND
Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events.


OBJECTIVE
To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors.


METHODS
Randomized, single-blind, placebo-controlled trial.


METHODS
40 men with adult-onset growth hormone deficiency.


METHODS
Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level.


METHODS
Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months.


RESULTS
C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087).


CONCLUSIONS
Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.
Sesmilo
G
G
Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Biller
B M
BM
Llevadot
J
J
Hayden
D
D
Hanson
G
G
Rifai
N
N
Klibanski
A
A
D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D000704:Analysis of Variance; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D019382:Human Growth Hormone / Q000009:adverse effects* / Q000172:deficiency*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D016037:Single-Blind Method
D001786:Blood Glucose; D015850:Interleukin-6; D008055:Lipids; D010919:Placebos; D000685:Serum Amyloid A Protein; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein