Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency

Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency

A Randomized, Controlled Clinical Trial

From Massachusetts General Hospital, Harvard Medical School, Brigham and Women's Hospital, and Children's Hospital, Boston, Massachusetts.

Abstract

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 A_1c, 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 A_1c 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.

Article and Author Information

Acknowledgments: The authors thank Howard Baum, MD, and the staff of the General Clinical Research Center for patient recruitment and care. They also thank David Schoenfeld, PhD, for statistical advice.
Grant Support: In part by National Institutes of Health grants RR 1066 and DK08783 and Genentech, Inc. Drs. Sesmilo and Llevadot are supported by Fundació “la Caixa,” Barcelona, Spain.
Requests for Single Reprints: Anne Klibanski, MD, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 457B, Boston, MA 02114.
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Current Author Addresses: Drs. Sesmilo, Biller, and Klibanski: Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 457 B, Boston, MA 02114.
Dr. Llevadot: TIMI Office, Brigham and Women's Hospital, 333 Longwood Avenue, Suite 402, Boston, MA 02115.
Dr. Rifai and Ms. Hanson: Department of Laboratory Medicine and Pathology, Children's Hospital, 300 Longwood Avenue, Farley 7, Boston, MA 02115.
Mr. Hayden: Biostatistics Center, Massachusetts General Hospital, 50 Staniford Street, 5th Floor, Boston, MA 02114.
Author Contributions: Conception and design: G. Sesmilo, B.M.K. Biller, J. Llevadot, N. Rifai, A. Klibanski.
Analysis and interpretation of the data: G. Sesmilo, J. Llevadot, N. Rifai, G. Hanson, D. Hayden, A. Klibanski.
Drafting of the article: G. Sesmilo, A. Klibanski.
Critical revision of the article for important intellectual content: G. Sesmilo, B.M.K. Biller, J. Llevadot, N. Rifai, D. Hayden, A. Klibanski.
Final approval of the article: G. Sesmilo, B.M.K. Biller, J. Llevadot, N. Rifai, G. Hanson, D. Hayden, A. Klibanski.
Provision of study materials or patients: G. Sesmilo, B.M.K. Biller, A. Klibanski.
Statistical expertise: D. Hayden.
Obtaining of funding: B.M.K. Biller.
Administrative, technical, or logistic support: B.M.K. Biller, G. Hanson.
Collection and assembly of data: G. Sesmilo, B.M.K. Biller, G. Hanson, D. Hayden, A. Klibanski.