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Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency: A Randomized, Controlled Clinical Trial

Gemma Sesmilo, MD; Beverly M.K. Biller, MD; Joan Llevadot, MD, PhD; Douglas Hayden, MA; Greta Hanson, BS; Nader Rifai, PhD; and Anne Klibanski, MD
[+] Article and Author Information

Copyright ©2004 by the American College of Physicians


Ann Intern Med. 2000;133(2):111-122. doi:10.7326/0003-4819-133-2-200007180-00010
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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.

Figures

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Figure 1.
Central fat ratios and inflammatory markers in growth hormone (black circles) and placebo (white circles) recipients.PP

Error bars represent 1 SD. values for the mean difference between groups over months 6, 12, and 18 were 0.0087 for truncal fat–to–total fat ratio and 0.052 for truncal fat–to–extremity fat ratio. values for the mean difference between groups over months 6 and 18 were 0.0027 for C-reactive protein levels, 0.013 for interleukin-6 levels, and 0.056 for serum amyloid polypeptide A levels.

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Figure 2.
Lipid values and lipoprotein(a) levels in growth hormone (black circles) and placebo (white circles) recipients.PHDLLDLP

Error bars represent 1 SD. values for the mean difference between groups over months 1 and 3 were <0.001 for total cholesterol levels, 0.10 for high-density lipoprotein ( ) cholesterol levels, and <0.001 for low-density lipoprotein ( ) cholesterol levels. values for the mean difference between groups over months 6 to 18 were >0.2 for total cholesterol levels, >0.2 for HDL cholesterol levels, 0.15 for LDL cholesterol levels, and <0.001 for lipoprotein(a) levels. To convert total, HDL, and LDL cholesterol values to mg/dL, divide by 0.0286.

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Figure 3.
Glucose and insulin levels in growth hormone (black circles) and placebo (white circles) recipients.PP

Error bars represent 1 SD. values for the mean difference between groups over months 1 and 3 were 0.0018 for glucose levels and <0.001 for insulin levels. values for the mean differences between groups over months 6 to 18 were 0.0026 for glucose levels and 0.064 for insulin levels. To convert glucose values to mg/dL, divide by 0.0555.

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