Uncovering Growth Hormone
by: Guy daSilva, MDWednesday, June 18, 2008
What is Growth Hormone (hGH or GH for short)
Like all other hormones it is a messenger. It is neither more important nor less important than any other hormone. It is neither more dangerous nor more beneficial than any other hormone. As with other hormones, there are side effects if it is too low or too high. Many believe it is a “steroid” when in actuality it is a protein molecule, 191 amino acids long. Human growth hormone (hGH) is a natural hormone produced in the human body by the pituitary gland. It's available as a pharmaceutically produced injectable, which has become a popular but expensive “medication” prescribed in height difficulties in children, adult growth hormone deficiency syndrome (AGHDS) and in the treatment of AIDS-related wasting.
History of Growth Hormone
Growth Hormone was discovered in 1920. By 1958 Dr. Maurice Raben injected hGH into a dwarf child, who then grew normally within two years. The child was a nine-year old with a stature of a six-year old. After two years on hGH, he was no different than any other child in that age bracket. This was the answer to prayer for tens of thousands of people until 1980 when the governement was forced to take Growth Hormone off the market due to an outbreak of Creutzfeldt-Jakob Disease, a type of “mad cow’s” disease, in 9 children. At the time, Growth Hormone was obtained from cadaver pituitary glands, mostly from Africa, and it took one thousand of these glands to get a year supply of Growth Hormone for one child.
The “Orhan Drug Act” revitalized Growth Hormone in 1985. The act allowed four pharmaceutical companies to apply DNA recombinant drug engineering to make the hormone. These companies would be offered open contracts with an unlimited patent of 20 to 25 years instead of seven, which drove up the expense of the hormone to the consumer.
In the last year, human growth hormone abuse has had heavy press coverage, especially since the revelation that pitcher Jason Grimsley of the Arizona Diamondbacks told federal investigators that he and others in Major League Baseball have been using hGH as an alternative to anabolic steroids for performance enhancement. Even before the whole Grimsley situation came to light, positive reports about hGH replacement were generally few and far between in mainstream media; the vast majority were negative.
Back in March 2006, there was a news piece about hGH in Brandweek magazine entitled “Bad Medicine,” which began: “Selling human growth hormone as an anti-aging drug is a federal crime.” That news piece stemmed from an article published in the Journal of the American Medical Association back in October 2005 entitled “Provision or Distribution of Growth Hormone for ‘Anti-Aging’: Clinical and Legal Issues.” The JAMA article attacked GH therapy and confused pharmaceutical hGH products and issues with homeopathic and supplement products and issues. Furthermore, JAMA refused to publish responses to the article from the anti-aging community, including numerous voices from the American Academy of Anti-Aging Medicine. The article and subsequent news pieces sent fear and uncertainty through the ranks of practitioners involved in the prescribing of hGH for adult growth hormone deficiency (AGHDS).
Thus, we have a cultural atmosphere in which positive research findings concerning hGH receive scant attention, but harsh criticism and negative attacks receive broad dissemination in both the scientific and lay press. While the anti-aging community organizes and mounts a defense, what are practitioners to do? What are the lawful reasons to prescribe hGH in the context of an anti-aging practice? What types of hGH are legal to prescribe? How can practitioners ensure compliance with the law in adult hormone replacement therapy? The aim of this paper is to help answer these questions.
The problem with growth hormone (GH) is that the law surrounding its use is tricky and the
bottom line is that it should only be used on-label in anti-aging– i.e., for the treatment of adult GH deficiency. GH is associated with numerous benefits. In the shadow of its benefits, the main question virtually everyone asks about GH is: “Does GH cause cancer?” Extensive studies of the outcome of GH replacement in childhood cancer survivors, have uncovered no evidence of de novo cancers. More recent surveillance of children and adults treated with GH has found that there is no increase in observed cancer risk.
In this paper, I have researched the medical literature and will attempt to answer some of the riveting questions surrounding one of the most researched, yet highly controversial “substances” in medical history, human Growth Hormone.
The Physiology
After age 30, we lose about one-pound of muscle per year, which exactly correlates to the 1% of growth hormone loss we suffer from each and every year after that same age. The symptoms of Adult Growth Hormone Deficiency are:
- • Loss of strength
- • Loss of exercise capacity
- • Osteopenia (loss of bone)
- • Sarcopenia (loss of muscle)
- • Increased total and intra-abdominal fat
- • Glucose intolerance leading to insulin resistant diabetes
- • Dyslipidemia- high cholesterol, LDL & Triglycerides and low HDL
- • Increased fragility of skin and blood vessels
- • Decreased immune function
- • Decreased quality of life
So it is no wonder that as we age our bones get weaker, out heart becomes diseased, our muscle mass dwindles and our fat appears to accumulate… and on and on.
At age 60 most adults have total 24-hour secretion rates of growth hormone that are indistinguishable from those of hypopituitary patients with organic lesions in the pituitary gland. (Savine, R., et al., “Growth hormone replacement for the somatopause,” Horm Res 2000; 53(Suppl 3):37- 41. Simpson, H., et al., “Growth hormone replacement therapy for adults: into the new millennium,” Growth Hormone & IGF Research 2002; 12:1-33).
Clinical Studies and Major Articles
A recent search in Pub Med reveals over 87,000 publications on growth hormone in the conventional medical literature. Yet mainstream medicine and the media continually remark how under-studied this hormone is. In addition, there are 384 double blind placebo control studies on growth hormone, some of which I will highlight below.
A landmark study by Dr. Rudman from Harvard (NEJM 323:1-6 July 5, 1990) looked at growth hormone’s effects on body composition in the elderly. In essence, Dr. Rudman studied 12 elderly men in a nursing home, ages ranging from 61-80 years old, that were given 3 injections of hGH per week at a high dose of 5mg/day. As a control, 9 elderly men received placebo.
The results of the study are summarized below:
- • 14% decrease in body fat (3.5kg/7 pounds loss)
- • 8.8% increase in lean body mass
- • Increased bone density (from -1.1 to -0.9)
- • Increased skin thickness
- • Side effects: Edema and increased blood sugar
In the article Dr. Rudman remarked that he knew just from walking into the nursing home, who was on the hormone and who was on the placebo. Unfortunately, the investigators feared the side effects of giving these men growth hormone (edema and increased blood sugar) and did no further investigation.
Dr. Rudman’s study soon received disbelief and was later re-produced by Dr. Papadakis at the University of California San Francisco (Ann Intern Med 1996:124:708-716)
The repeat study revealed similar results within six-months including:
- • Decreased in fat mass of 13.1%
- • Increase in lean mass of 4.3%
- • Increase in bone mineral content of 0.9%
- • Increase in skin thickness of 13.4%
- • Increase in muscle strength of 10%
- • Increase in oxygen consumption of 2.5%
Human growth hormone (GH) should actually be called “repair hormone”. The following sub-headings will substantiate this claim and hopefully open your minds to this amazing hormone.
GH and Memory
A 2000 study by Dr. Nyberg showed that growth hormone was responsible for improving cognitive capabilities, memory, alertness, motivation, and work capacity (Nyberg, F., et al., “Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance,” Frontiers in Neuroendocrinol 2000; 21(4):330-348).
GH and Alzheimer’s
Numerous clinical studies have proven that growth hormone has protection against the mechanism that causes Alzheimer’s Disease by exerting cytoprotection against A beta amyloid plaques that induce neuronal cell death (Takako Niikura et al. Insulin-Like Growth Factor 1 (IGF-1 Protects cells from Apoptosis by Alzeheimer’s V6421 Mutant Amyloid Precursor Protein through IGF-1 Receptor in an IGF-Binding Protein-Sensitive Manner. The Journal of Neuroscience, March 15, 2001, (21(6):1902-1910).
GH and Bone
Growth Hormone has been shown to increase the formation and strength of cortical bone, thus decreasing and even reversing osteoporosis (Sugimoto, T., et al., “Effect of recombinant human growth hormone in elderly osteoporotic women,” Clin Endocrinol (Oxf) 1999; 51(6):715-124;
Baum, H., et al., “Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial,” Ann Intern Med 1996; 125(11):883-90).
GH and the Heart
Growth Hormone improves cardiac contractility, cardiac output and ejection fraction. A 1999 study showed how growth hormone improved cardiac function after myocardial infarction by stimulating contractility and promoting tissue remodeling. The same study showed how growth hormone facilitates glucose metabolism, lowers insulin levels, increases insulin sensitivity, and improves the lipid profile (Ren, J., et al., “Insulin-like growth factor 1 as a cardiac hormone: physiological and pathophysiological implications in heart disease,” Journ Mol Cell Cardiol 1999; 31(11):2049-61).
GH and Immune System
Insulin Growth Factor-1 (IGF-1) is a powerful hormone of growth created by growth hormone in the liver. IGF-1 is needed for lymphocyte maturation and function. Decline in T and B cells are restored with GH. IGF-1 restores damaged immune system (Burgess, W., et al., “The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-1,” Neuroimmunomodulation 1999; 6(1-2):56-68).
GH and Obesity
GH decreases adiposity or fat by it’s inhibition of lipoprotein lipase, which enhances lipolysis and improves dyslipidemia (Nam, S., et al., “Growth hormone and adipocyte function in obesity,” Horm Res 2000; 53(Suppl 1):87-97).
Contraindications to GH Replacement
The package insert comments that growth hormone should not be used in patients with “Proliferative retinopathy” or “Active malignancy”; however, the president of the Growth Hormone Research Society stated that, “There are no data to support this labeling. Current knowledge does not warrant additional warning about cancer risk”. There is no evidence that GH increases cancer recurrence or de novo cancer or leukemia. There is an increased risk of cancer, however, in low growth hormone adults, (Journal of Clinical Endocrine Metabolism, May 2001)
GH and Cancer
A review of the existing literature regarding growth hormone and cancer by Shalet states that tumor recurrence is not greater than in patients not on GH and that there is no increase in cancer in children on GH replacement. Concluding that there is “No evidence of an increased risk of malignancy, recurrent or de novo.” (Shalet, S., et al., “Growth hormone therapy and malignancy,” Horm Res 1997; 48 (Suppl 4):29-32).
One study that does implicates growth hormone with cancer is by Jenkins in the Journal of Clinical Endocrinology and Metabolism, 2000, volume 85: pages 3218-3221. Jenkins concluded that there is a positive influence of IGF-1 in cancer development is supported by the consideralbe evidence that patients with acromegaly are at an increased risk of cancer, especially colorectal.
Jenkins failed to realized however, that in acromegalic patients the IGF-1 levels are much greater than that of normal values. Realizing that it’s the imbalance of hormones that allows mutated cells to proliferate.
A quote from a 1999 New England Journal of Medicine article states that there is “No evidence that GH replacement therapy affects the risk of cancer or cardiovascular disease” (Vance M. et al. GH Therapy in Adults and Children. New England Journal of Medicine October 14, 1999).
A remarkable study of children with brain tumors, and cranial radiotherapy who were given growth hormone (180 treated with GH and 891 not treated with GH) revealed the following:
In treated patients:
Decreased risk of recurrence- 0.6RR
Decreased risk of mortality- 0.55 RR
(Swerdlow A. et al. Growth Hormone Treatment of Children with Brain Tumors and Risk of Tumor recurrence. The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 12, December 2000).
Does GH cause cancer?
“Extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increased in observed cancer risk.” (Jenkins PJ et al. Does growth hormone cause cancer? Clin Endocrinol (Oxf). 2006 Feb;64)2):115-21).
Side Effects of GH Replacement
I once heard the Senior Medical Correspondent for CNN state on TV that growth hormone has some very serious side-effects such as edema and arthralgias. Yet each evening, numerous commercials for pharmaceutical drugs rattle off some very serous side-effects of commonly prescribed medications, which sometimes include death.
But to remark on growth hormone’s side-effects, it is commonly related to a low frequency high dose schedule, which is reversible with a decrease of the dose (Vance, M., et al., “GH therapy in adults and children,” NEJM 1999; October 14).
Other side effects related to non-physiologic, high dose use of growth hormone includes:
- • Edema
- • Arthralgia
- • Carpal tunnel syndrome
- • Hypertension
- • Glucose intolerance/Insulin resistance
Benefits of GH Replacement
To date, more than 100,000 patients worldwide have received hGH therapy. Available data is scarce and follow up time is short. Data to date does not suggest that hGH therapy of adults with Growth Hormone Deficiency increases the risk of cancer, provided that IGF-1 levels remain with the normal range.
Instead Growth Hormone replacement is responsible for:
- • Growth
- • Healing
- • Increased muscle mass
- • Minimizing body fat
- • Controlling cholesterol
- • Maintaining levels of sexual energy and enhanced sexual performance
- • Increased bone strength
- • Improvement in cardiovascular function and lipids
- • Reversing atherosclerotic changes in carotids
- • Quality of life improvement
- • Increased Bone mineral density
- • Improved memory, alertness, and concentration
- • Higher energy level
- • Superior immune function
- • Lowered blood pressure
- • Younger, tighter, thicker skin
- • Wrinkle removal
- • Elimination of cellulite
- • Sharper vision
- • Improved sleep
- • Less Morbidity and Mortality from cardiovascular disease
- • Body composition: Bone muscle, fat, visceral fat
- • Less inflammation
- • Less sick days
- • Improved exercise capacity (strength)
Cook DM. Shouldn’t adults with growth hormone deficiency be offered growth hormone replacement therapy? Ann Intern Med 2002 Aug 6;137(3):197-201
Conclusion
Growth Hormone treatment of adults with Growth Hormone Deficiency is safe. “Although there has been some concern about an increased risk of cancer, reviews of existing, well-maintained databases of treated patients have shown this theoretical risk to be non-existent (Molitch ME. Diagnosis of GH deficiency in adults- how good do the criteria need to be? J Clin Endocrinol Metab 2002 Feb;87(2):473-6)
“Growth Hormone is essential for normal adult life, and without it life expectancy is shortened, energy and vitality reduced and the quality of this life is impaired. The medical case for GH replacement is now proven beyond any reasonable medical and scientific doubt.” (Peter H Sonksen, MD, Growth Hormone & IGF-1 Research 1998, 8, 275-276)
