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Posted on Nov 10, 2003, 6 a.m.
By Bill Freeman
On July 5, 1990, an article by Dr. Daniel Rudman and colleagues at the Medical College of Wisconsin appearing in the New England Journal of Medicine established one of the most important milestones in the history of clinical anti-aging medicine. Rudman's article documented the world's first clinical trial of human growth hormone (HGH) replacement in elderly men.
On July 5, 1990, an article by Dr. Daniel Rudman and colleagues at the Medical College of Wisconsin appearing in the New England Journal of Medicine established one of the most important milestones in the history of clinical anti-aging medicine. Rudman's article documented the world's first clinical trial of human growth hormone (HGH) replacement in elderly men. Comparing the effects of six months' of HGH injections on twelve men, ages 61 to 81, with an age-matched control group, the researchers showed clear benefits to the therapy. Men administered HGH gained an average of 8.8% in lean body mass and lost 14% in fat (without diet or exercise), improved their skin texture and tone, and increased their bone density. In language rarely used in conservative medical journals, the researchers wrote: "The effects of six months of human growth hormone on lean body mass and adiposetissue mass were equivalent in magnitude to the changes incurred during 10 to 20 years of aging."
Twelve years after publication of that landmark research study, we review the current disposition of the utilization of human growth hormone therapy in adults. In the following abstracts review, we highlight research conducted in the past eighteen months, which continues to validate GH replacement in improving body composition, cardiac function, and bone density. Additionally, exciting new research is now elucidating the value of GH therapy in treating specific diseases - including HIV and liver disease. We also share perspectives from two leading anti-aging clinicians on the application of growth hormone as an anti-aging intervention.
Abstracts Review
Body Composition-Cardiac Function-Bone Density
JUNE 2002 (University of Toronto, Toronto, Ontario, Canada): Dr. Ezzat and colleagues administered GH to 67 men and 48 women found to be growth hormone deficient. After a six-month treatment period, lean body mass increased by an average of 2.1 kg, fat mass decreased by 2.8 kg, left ventricular systolic function greatly improved and ejection fraction was significantly restored ("approaching normalcy"). GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. In both men and women, the researchers found: "No apparent relationship between IGF-I levels and the occurrence or severity of adverse events. GH replacement therapy in adults demonstrated beneficial effects on lean body mass composition [and] cardiac function improvement."
APRIL 2002 (Hypoptiuitary Control and Complications Study International Advisory Board [an organization studying the efficacy and safety of GH therapy of adult GHdeficient patients in clinical practice]): Dr. Attanasio and colleagues reported on a three-year course of GH therapy administered to adult onset GH-deficient patients. Lean body mass increase was found to be greatest in the those younger than 40 years old, less but still significant in the middle group (40- 60 years), and unchanged in the oldest (>60 years). Conversely, decreases in the low density lipoprotein/HDL ratio were insignificant in the younger patients, but proved to be significant in the middle and older age groups. The researchers submit that "these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important predictor of response."
OCTOBER 2001 (University Hospital, Goetburg, Sweden): Dr. Gotherstrom and colleagues at the Research Centre for Endocrinology and Metabolism studied a five-year course of GH replacement in 70 men and 48 women (mean age 49.3 years), with adult-onset GH deficiency. They found a sustained increase in lean body mass and a decrease in body fat. The GH treatment increased total body bone mineral content as well as lumbar and femur neck bone mineral content. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. Serum concentrations of triglycerides and hemoglobin A(1c) were reduced. In conclusion, the researchers state: "Five years of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment."
OCTOBER 2001 (University Hospital, Uppsala, Sweden): Dr. Gillberg and team found that three months of low-dose GH on 64 GHdeficient adults increased serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and lipoprotein (a), reduced total and low density lipoprotein cholesterol levels, and resulted with greater lean body mass and decreased fat mass. The researchers suggest, "This fixed low-dose regime resulted in improvements in body composition and lipid profile, without causing serious side effects. This is therefore a valid method to institute GH replacement in adults."
Cardiovascular System
APRIL 2002 (The Christie Hospital, Manchester, United Kingdom): Treating 67 GH deficient adults with a titered low-dose GH regimen designed to normalize serum IGF-1, Dr. Murray and co-researchers observed significant improvements in total cholesterol, LDL, triglycerides, and the ratio of total cholesterol to HDL. They reported observing the greatest improvements in patients with the most adverse lipid profiles at the start of GH treatment.
APRIL 2002 (University Hospital of Wales): Dr. Smith and colleagues administered GH to 19 men and 13 women (age range 19 to 64 years) over a three-month period. GH replacement resulted in increases in lipid hydroperoxides in plasma and neutrophil O(-)(2)- generating capacity. The researchers conclude that these marker improvements reduce oxidative stress, thereby mediating endothelial dysfunction that frequently results with a pro-atherogenic state associated with adult GHD.
Bone Density
JUNE 2002 (National University Hospital, Oslo, Norway): In a course of twelve-months of GH replacement in 9 women and 16 men (mean age 46 years) with GH deficiency, Dr. Ueland and team found that bone mass and skeletal biomechanical competence were improved specifically as a result of GH treatment-related increases the accumulation of IGF-I and OPG in cortical and trabecular bone.
JULY 2001 (University of Bochum, Germany): In a six-year long study, Dr. Clanget and colleagues replaced GH in 4 women and 8 men (mean age 42.5 years) with GH deficiency. As a result, bone mineral density at the lumbar spine increased by 15.9%, and was paralleled by similar increases in the lumbar vertebrae. They conclude that "GH therapy in GH-deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years."
Specific Disease Treatment
JUNE 2002 (University of Queensland, Princess Alexandra Hospital, Australia): Nine adults with mild- to moderate-severity chronic liver disease (etiologies including alcohol and primary bilary cirrhosis) were treated with GH. Increases in serum IGF-1, IGFBP-3, improvements in body weight and resting metabolic rate were noted. Additonally, significant increases in whole-body protein catabolism, lipolysis and lipid oxidation, and insulin resistance were observed.
MAY 2002 (University of California San Francisco): Dr. Napolitano and colleagues at the Gladstone Institute of Virology and Immunology administered GH to five male HIV patients for six months. In all five subjects, GH treatment resulted in a marked increase in thymic mass, and significant increase in circulating naive CD4 T cells. The researchers conclude that "GH has significant effects on the human immune system, including the reversal of thymic atrophy in HIV-1-infected adults. De-novo T cell production may thus be inducible in immunodeficient adults."
JANUARY 2002 (University Federico II School of Medicine, Naples, Italy): Dr. Napoli and team found that a three-month treatment with GH in patients with chronic heart failure corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation. Specifically, they attributed these benefits to GH's improvement of vascular reactivity. State the researchers: "The data highlight the potential role of GH in the progression of congestive heart failure."
DECEMBER 2001 (Shimane Medical University, Izumo, Japan): Dr. Sohmiya and colleagues administered GH to eight anemic patients with adult GH deficiency. Erythropoietin secretion was stimulated within two weeks, and increased hemoglobin concentrations were observed after ten months of GH therapy. The researchers, noting that long-term administration of GH stimulates erythroid cells, conclude that there is "a beneficial effect of GH replacement in anemic patients with adult GH deficiency."
An original article as appeared in Anti-Aging Medical News, Summer-Fall 2002, published by the A4M.
