Growth Hormone is a hormone composed of a long chain of amino acids, 191 to be exact. Under normal physiologic conditions, growth hormone is secreted by the anterior pituitary gland. This is a gland that lies at the base of the brain in a bony cavity called the Sella Turcica. In addition to growth hormone, the anterior pituitary also secretes prolactin, thyroid stimulating hormone, luteinizing hormone, follicle stimulating hormone, and adrenal corticotrophin hormone. The secretion of growth hormone by the pituitary gland is initiated by the hypothalamus, another gland in the brain that lies right next to the pituitary. The hypothalamus initiates growth hormone secretion by secreting growth hormone releasing hormone (GHRH); when GHRH is turned on, the pituitary will release growth hormone in bursts of activity. These bursts of growth hormone release occur primarily during deep stages of sleep.
Once released in the blood, growth hormone is very short lived. It is generally completely metabolized and gone within a half-hour. During that time, however, it manages to reach the liver and many other cells in the body, and induce them to make another polypeptide hormone called Insulin-like Growth Factor One (IGF-1). It is really IGF-1 that travels around to the various tissues of the body to affect most of the benefits that we attribute to growth hormone. The secretion of growth hormone itself is regulated by a classic biofeedback loop. This means when levels of growth hormone in the blood reach a certain threshold, growth hormone stimulates receptors in the pituitary to stop further growth hormone secretion. It also stimulates receptors in the hypothalamus to stop GHRH and turn on somatostatin. IGF- 1, which goes up in response to growth hormone, also feeds back on the pituitary and hypothalamus to help control growth hormone secretion, This is nature’s system of checks and balances to assure we don’t have too much of any one hormone.
NOMENCLATURE
The nomenclature for growth hormone is a bit complicated, but understanding it from the beginning can save much confusion in the future. Somatropin refers to growth hormone of the same amino acid sequence as the naturally occurring growth hormone.
Manufactured growth hormone is made by recombinant DNA technology. This is a system of genetically modifying either bacteria cells or mammalian cells in tissue culture which contains the gene that directs the cell to make human growth hormone. As the cells in the tissue culture grow and function, they will synthesize human growth hormone. Since this is a natural process, human growth hormone is not considered a synthetic.
The proper abbreviation for manufactured (recombinant) human growth hormone is rhGH. Unfortunately, the abbreviations have been misused even in the medical community, and recombinant human growth hormone is commonly represented by the abbreviation HGH.
The designation is no longer critical since human growth hormone of pituitary origin is no longer used in the United States. The term hGH or GH therefore, refers to human growth hormone from recombinant DNA technology. It is pure and 100% free of any contaminants or microorganisms.
HISTORY
Prior to the advent of recombinant DNA technology, the only source of growth hormone was from human cadavers. More than 27,000 children worldwide were treated with growth hormone of this source (pit-hGH). Due to short supply, children were treated with low doses and interrupted regimens as a result their response and ultimate height was mitigated. Distribution of pit-hGH was stopped in the United States and most of Europe in 1985, with the emergence of Creutzfeldt Jakob disease. This is a rare and fatal spongiform encephalopathy, caused by a small pathogen called a Prion. This is the same pathogen that causes “Mad Cow Disease” recently seen in Europe from infected cattle. It is impossible to catch Creutzfeldt-Jakob disease or any other infection from recombinant human growth hormone because it is not derived from a human or animal source, but from a purified tissue culture.
The bio-potency of commercially available growth hormone is typically represented by either milligrams or units to put it simply; 1 milligram of growth hormone is equivalent to 3 units. The international units were developed by the World Health Organization in order to standardize growth hormone preparations because of the various production techniques used early on in the manufacturing process. By now, the manufacturing process has been streamlined and largely perfected so the bio-equivalency of the various brands of growth hormone (at least those manufactured and approved by the FDA for sale in the United States) is identical. Therefore, a typical 18-unit vial of growth hormone contains 6mg.
USES OF GROWTH HORMONE
Growth hormone was initially used for children of short stature who are growth hormone deficient either because of an inactive pituitary, a tumor of the pituitary, or destruction of the pituitary by surgery or by radiation to remove a tumor. The other pituitary hormones were replaced along with GH. Growth hormone was used only until the children reached an acceptable adult height and then it was stopped because it was thought to be useful only for growth.
It wasn’t until much later that adult growth hormone deficiency was recognized to be a problem. It was discovered that adults who were deficient in growth hormone suffered from premature cardiovascular disease, reduced bone density, central obesity, decreased muscle mass, depressed mood, elevated levels of LDL (bad) cholesterol, slower wound healing, fatigue, poor exercise tolerance and poor immune function. At that point the use of growth hormone began in this unfortunate population, resulting in improvement of all of the above. It wasn’t until 1990, however, that the benefits of growth hormone and the treatment of normal aging were recognized.
SOMATOPAUSE
Somatopause is an extrapolation of the term “menopause”. Menopause is the condition in women whereby the ovaries atrophy and cease to produce the sex hormones Estrogen, Progesterone and Testosterone. Somatopause signifies the gradual decline in growth hormone production by the adult pituitary gland in both men and women that begins at approximately age 30 and continues at a steady rate throughout life. The decline in growth hormone level that occurs with Somatopause is accompanied by deterioration in the structure and functional capacity of our body, which is ultimately devastating to the human condition. This can be interpreted as the aging process. In fact there is absolutely no difference between the clinical signs and symptoms of aging and those of adult growth hormone deficiency as described above.
TREATMENT REGIMENS
Growth hormone can be given either subcutaneous or by intra-muscular injection with equal therapeutic activity. Subcutaneous administration is now used almost exclusively because intra-muscular administration is fraught with an increase in side effects without any additional therapeutic benefit. The reason for this has to do with the biofeedback mechanism for growth hormone. Most of our natural pituitary growth hormone secretion occurs at night during deep stages of sleep. Injecting growth hormone at night raises the serum level of growth hormone precisely during the time the pituitary is scheduled to become active, this high serum level of growth hormone from the injection can suppress our natural pituitary function by negative feedback. We then not only lose the benefit of our own endogenous growth hormone, but also run the risk of suppressing the pituitary, thus making it easy”. For the most part, the pituitary has completed its function and is at rest by 5 a.m. Therefore injecting after awakening in the morning results on top of the peak of endogenous (our own) growth hormone, so as not to suppress the pituitary. By the time the pituitary is ready again for its nighttime activity, the growth hormone given in the morning injection has been completely metabolized. This eliminates the risk of pituitary suppression.
BENEFITS
The benefits of growth hormone use in Somatopause which have been clearly documented in the medical literature include the following: a decrease in body fat, an increase in muscle mass, thickening of the skin with decreased wrinkling, improvement in the cholesterol profile, an increase in bone density, enhanced feeling of well being, a decrease in The waist to hip ratio (meaning fat is removed primarily from around the waist where it is associated with a high risk of coronary disease), improvement in aerobic capacity, enhanced immune function and a decrease in the frequency of illness.
SIDE EFFECTS
Side effects of growth hormone are generally mild and are largely associated with salt and water retention. The minority of patients that experience this typically complain of mild weight gain from water retention associated with a vague feeling of puffiness. This is sometimes accompanied by joint discomfort particularly in the fingers, with a feeling of tightness when making a fist. Other joints may also become uncomfortable.
Carpal Tunnel Syndrome is a well-known side effect of growth hormone that was more common in the early days when growth hormone was given in higher dose with lower frequency. Carpal Tunnel Syndrome is also a function of fluid retention, which causes water to accumulate in the closed carpal tunnel compartment of the wrist compressing the median nerve. This results in numbness and tingling in the palm and fingers. Abstaining from growth hormone for about a week, and then resuming the treatment with a 20% dose reduction easily remedy these side effects.
Older patients are more subject to side effects and are generally started at a low dose of growth hormone than younger adults. Another potential side effect of growth hormone is the elevation of blood sugar. Growth hormone mobilizes body fat, causing our fat cells to break Themselves down and release free fatty’ acids into the blood stream. These free fatty acids are energy molecules, which can be taken up by organs and many of our organs to be used for energy. When our muscles are consuming free fatty acids as a fuel, they are far less interested in sugar, therefore they tend to resist the effects of insulin, and extract less sugar from the blood. At the same time, growth hormone can increase glucose output from the liver to the blood. This combination of effects can raise blood sugar and raise insulin levels, neither of which is good. Fortunately, this is only a problem in people who eat a diet high in sugar and starch, and do little exercise.
ACROMEGALY
Acromegaly and gigantism are diseases of growth hormone excess. These are typically seen by persons who have growth hormone secreting tumors. Gigantism refers to the condition of growth hormone excess in children, where their ultimate height is far above normal because the growth hormone excess occurs when the epiphyseal plates of the bones are still open and the bones are growing. Acromegaly refers to growth hormone excess in adulthood after the epiphyses are closed and the bones are no longer growing. In these people the cartilage continues to grow, and the disease is characterized by enlargement of the nose, chin, ears, supra-orbital ridge (eyebrow area), hands and feet.
Patients occasionally ask if Acromegaly can result from growth hormone supplementation in adulthood. The answer is absolutely not. Acromegaly results in growth hormone levels that are two to ten times that of a normal adult. Keep in mind that when we supplement growth hormone in a controlled and monitored medical program, we bring the level only up to the mid-normal range of an adult. In fact one would have to use ridiculously high doses by today’s standards to achieve the growth hormone levels seen in Acromegaly.
Patients with Acromegaly also afforded a research group at UCLA Department of Endocrinology an opportunity to answer questions about cancer risks from use of Growth Hormone. In the November 1999 journal, Hormone Research, published by the Division of Pediatric Endocrinology, UCLA, Los Angeles, Calif., USA, they stated” Increased GH levels as seen in Acromegaly has been associated with Benign Prostatic Hyperplasia(BPH) but not with prostate, breast or lung cancers..” In fact, there are very few articles that support the notion that growth hormone cause any kind of cancer. Reports from John Hopkins research of acromegaly patients followed in from 1870s to 1950s showed decreased incidence of cancer, and these were patients with growth hormone levels 2-10 times the high normal level throughout a lifetime.
MONITORING
Since growth hormone is metabolized so quickly, it is not easily measured in a blood test. The levels fluctuate widely, and measuring growth hormone is notoriously inaccurate. The best laboratory marker we have for growth hormone is the measurement of Insulin-like Growth Factor One (IGF-l). IGF-l levels are much more stable in The blood and not only reflect the average daily growth hormone level, but directly reflect growth hormone activity; because IGF-l is the hormone that carries out most of The benefits of growth hormone. So, despite claims about its shortcomings, it remains an excellent marker of growth hormone effect and certainly the best one available in the laboratory. There is one better marker of the benefit of growth hormone, however. It’s what we call the “clinical benefit. This is the feedback we get from patients who are taking growth hormone.
How they are feeling in terms of energy, well being, body composition, frequency of illness, their own physical appearance etc. is far more valuable a marker than any blood test can be. What we really use the IGF-1 level for is to be certain beyond a doubt that we’re not giving too much growth hormone. We titrated the dose of growth hormone to get an optimal clinical response (a happy patient) even if the IGF-1 hasn’t reached a particular goal range. This often allows us to limit the dose and minimize patient costs. After all, we’re treating the patient not the blood test.
SUMMARY
Originally taken only from human cadavers, and used only in children of short stature, growth hormone has had an interesting and controversial history. Fortunately, the understanding of its importance in adult physiology came at approximately the same time as recombinant DNA technology, which led to greater availability along with virtual safety. Soon after this, the comparison was made between growth hormone deficient adults and aging adults. Because of the tremendous similarities, growth hormone began to be used and soon gained great popularity in the treatment of normal aging. Growth hormone is clearly useful and therapeutic in this regard as long as it is used in a carefully monitored, professionally managed program. Any growth hormone program must include proper nutrition and exercise with emphasis on a low refined carbohydrate diet.
CONCLUSION:
I make the following recommendations for anyone considering a program of Comprehensive Hormone Replacement Therapy (CHRT); make sure that the Physician is a board certification from the American Academy of Anti Aging Medicine and are in good standings with their state board of medical examiners. This is the only means by which you can be assured that the physician is qualified and knowledgeable to diagnose and treat you.
Thank You,
Paul Budnick, M.D., F.A.A.E.M.
Medical Director
DreamBody Medical Centers
Recommended Reading; “Grow Young with HGH” by Ronald Klatz, “Naturally Raising Your HGH Levels” by Dickens Weatherby. Several others at Amazon Books.
