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.
Design: Randomized, single-blind, placebo-controlled trial.
Patients: 40 men with adult-onset growth hormone deficiency.
Intervention: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level.
Measurements: 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, interleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months.
Results: C-reactive protein and interleukin-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.