INTRODUCTION GrowthHormone is a polypeptide Hormone. This means it is composed of a long
chain of amino acids, 191 to be exact. Under normal physiologic conditions,
GrowthHormone 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 GrowthHormone, the anterior pituitary also secretes prolactin,
thyroid stimulating Hormone, luteinizing Hormone, follicle stimulating Hormone,
and adrenal corticotropic Hormone. The secretion of GrowthHormone by the
pituitary gland is initiated by the hypothalamus, another gland in the brain
that lies right next to the pituitary. The hypothalamus initiates GrowthHormone
secretion by secreting GrowthHormone releasing Hormone (GHRH); at the same time
it stops secreting a GrowthHormone inhibitory Hormone called somatostatin. When
somatostatin is turned off and GHRH is turned on, the pituitary will release
GrowthHormone in bursts of activity. These bursts of GrowthHormone release
occur primarily during deep stages of sleep, such as stage 3 and stage 4. Once
released in the blood, GrowthHormone 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 effect most of the benefits that we attribute to GrowthHormone. The
secretion of GrowthHormone itself is regulated by a classic biofeedback loop.
This means when levels of GrowthHormone in the blood reach a certain threshold,
GrowthHormone stimulates receptors in the pituitary to stop further GrowthHormone secretion. It also stimulates receptors in the hypothalamus to stop GHRH
and turn on somatostatin. IGF-1, which goes up in response to GrowthHormone,
also feeds back on the pituitary and hypothalamus to help control GrowthHormone
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 GrowthHormone is a bit complicated, but understanding it
from the beginning can save much confusion in the future. Somatropin refers to
GrowthHormone of the same amino acid sequence as the naturally occurring GrowthHormone. Somatropin extracted from the Human pituitary gland was originally
designated (hGH, or pit-hGH). Manufactured GrowthHormone is made by recombinant
DNA technology. This is a system of genetically modifying either bacteria cells
or mammalian cells in tissue culture so that they include in their genome, the
gene that directs the cell to make HumanGrowthHormone. As the cells in the
tissue culture grow and function, they will synthesize HumanGrowthHormone by
the exact same process in the Human pituitary. Since this is a natural process,
HumanGrowthHormone is not considered a synthetic. The proper abbreviation for
manufactured (recombinant) HumanGrowthHormone is rGH. Unfortunately, the
abbreviations have been misused even in the medical community, and recombinant
HumanGrowthHormone is commonly represented by the abbreviation hGH. The
designation is no longer critical since HumanGrowthHormone of pituitary origin
is no longer used in the United States, or anywhere in the world that I'm aware
of. The term hGH or GH therefore, refers to HumanGrowthHormone from
recombinant DNA technology. It is pure and 100% free of any contaminants or
micro-organisms.
HISTORY
Prior to the advent of recombinant DNA technology, the only source of GrowthHormone was from Human cadavers. More than 27,000 children worldwide were
treated with GrowthHormone 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 HumanGrowthHormone because it is not derived from a Human or animal source, but from
a purified tissue culture. For purposes of this discussion, the term GrowthHormone, GH or hGH will mean GrowthHormone made by recombinant DNA technology.
The bio-potency of commercially available GrowthHormone is typically
represented by either milligrams or units. To put it simply, 1 milligram of
GrowthHormone is equivalent to 3 units. The international units were developed
by the World Health Organization in order to standardize GrowthHormone
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 GrowthHormone (at least those manufactured and approved by the FDA for sale in the
United States) are identical. Therefore, a typical 15-unit vial of GrowthHormone contains 5 mg, and a 4-unit vial contains 1.33 mg.
USES OF GrowthHormone GrowthHormone was initially used for children of short stature who are GrowthHormone 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. GrowthHormone 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. The
other pituitary Hormones, however, which were thought to be more critical, were
continued throughout adulthood. It wasn't until much later that adult GrowthHormone deficiency was recognized to be a problem. It was discovered that adults
who were deficient in GrowthHormone 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
GrowthHormone began in this unfortunate population, resulting in improvement of
all of the above. It wasn't until 1990, however, that the benefits of GrowthHormone and the treatment of normal aging were recognized. The most recent new
use of GrowthHormone is for the treatment of AIDS Wasting Syndrome. This is the
condition of weakness, fatigue, and loss of muscle mass in AIDS patients. Since
we at Cenegenics??? specialize in metabolic and hormonal control of aging, we will
limit this discussion to the use of GrowthHormone in the treatment of normal
aging.
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 GrowthHormone 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 GrowthHormone 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. In
fact, there is absolutely no difference between the clinical signs and symptoms
of aging and those of adult GrowthHormone deficiency described above. The late
Dr. Daniel Rudman first described the benefits of GrowthHormone therapy in
normal aging adults. Dr. Rudman published a landmark article in the New England
Journal of Medicine on July 7th, 1990. In his article, Dr. Rudman showed that by
putting healthy aging men on GrowthHormone for six months, he was able to
decrease their body fat by 14.4%, increase muscle mass by 8.8%, increase skin
thickness by 7.1%, and increase lumbar bone density by 1.6%. These exciting
findings clearly inaugurated the movement to supplement GrowthHormone in
healthy aging adults, which today is becoming commonplace.
TREATMENT REGIMENS GrowthHormone can be given either subcutaneously 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. Back in Dr. Rudman's
time, GrowthHormone was typically dosed three times a week in what we now
consider a high dose regimen. People would typically receive 12-18 units per
week given in injections of 4-6 units, three times a week. Although great
benefits were seen, side effects were very common, and much more bothersome than
those we see today. Currently we use only about half the weekly dose used in Dr.
Rudman's study, by smaller and more frequent injections, which provide both a
better clinical response and far fewer side-effects. In one study on GrowthHormone deficient children, those that received daily injections increased their
height during the study period by 9.7 centimeters more than those who received
thrice-weekly injections. Besides the low dose-high frequency technique, the
physicians at Cenegenics??? also employ morning injections as opposed to evening.
The reason for this has to do with the biofeedback mechanism for GrowthHormone.
Most of our natural pituitary GrowthHormone secretion occurs at night during
deep stages of sleep. Injecting GrowthHormone at night raises the serum level
of GrowthHormone precisely during the time the pituitary is scheduled to become
active. This high serum level of GrowthHormone from the injection can suppress
our natural pituitary function by negative feedback. We then not only lose the
benefit of our own endogenous GrowthHormone, but also run the risk of
surpressing the pituitary, thus making it "lazy". 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 in injecting "on top of the
peak" of endogenous (our own) GrowthHormone, so as not to suppress the
pituitary. By the time the pituitary is ready again for its nighttime activity,
the GrowthHormone given in the morning injection has been completely
metabolized. This eliminates the risk of pituitary suppression.
BENEFITS
The benefits of GrowthHormone 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. The changes that our
patients at Cenegenics??? seem to be most pleased with are the elevation in mood,
increase in energy level, improved sleep, decrease in body fat, increase in
muscle mass and enhanced ability to handle adversity with confidence and
optimism.
SIDE-EFFECTS
Side effects of GrowthHormone 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 GrowthHormone that was more common in the early days
when GrowthHormone 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. These side
effects are easily remedied by abstaining from GrowthHormone for about a week,
and then resuming the treatment with a 20% dose reduction. Older patients are
more subject to side effects and are generally started at a low dose of GrowthHormone than younger adults. Another potential side-effect of GrowthHormone is
the elevation of blood sugar. GrowthHormone 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, GrowthHormone 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. At Cenegenics??? we teach our patients to eat a low glycemic diet (low
in sugar and starch) and exercise regularly. The effect of our nutrition and
exercise program in lowering blood glucose and insulin levels far outweighs the
effect of GrowthHormone in raising glucose and insulin levels. The net effect
in our patients, therefore, is the lowering of glucose and insulin levels. This
is a very health-promoting benefit that prevents disease and extends life span.
ACROMEGALY
Acromegaly and giantism are diseases of GrowthHormone excess. These are
typically seen by persons who have GrowthHormone secreting tumors. Giantism
refers to the condition of GrowthHormone excess in children, where their
ultimate height is far above normal because the GrowthHormone excess occurs
when the epiphyseal plates of the bones are still open and the bones are
growing. Acromegaly refers to GrowthHormone 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 GrowthHormone
supplementation in adulthood. The answer is absolutely not. Acromegaly results
in GrowthHormone levels that are two to ten times that of a normal adult. Keep
in mind that when we supplement GrowthHormone 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 GrowthHormone levels seen in acromegaly.
MONITORING
Since GrowthHormone is metabolized so quickly, it is not easily measured in a
blood test. The levels fluctuate widely, and measuring GrowthHormone is
notoriously inaccurate. The best laboratory marker we have for GrowthHormone is
the measurement of Insulin-like Growth Factor One (IGF-1). IGF-1 levels are much
more stable in the blood and not only reflect the average daily GrowthHormone
level, but directly reflect GrowthHormone activity; because IGF-1 is the
Hormone that carries out most of the benefits of GrowthHormone. So, despite
claims about its shortcomings, it remains an excellent marker of GrowthHormone
effect, and certainly the best one available in the laboratory. There is one
better marker of the benefit of GrowthHormone, however. It's what we call the
"clinical benefit". This is the feedback we get from patients who are taking
GrowthHormone. 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 GrowthHormone. We titrate the dose of GrowthHormone 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.
SECRETAGOGUES
Secretagogues are preparations taken orally that are designed to stimulate the
pituitary to secret more of our own (endogenous) GrowthHormone. Secretagogues
are composed of amino acids or chains of amino acids called peptides. The
usefulness and benefit of these products is extremely variable, with the benefit
ranging from moderate to none whatsoever. A very large, and unfortunately, very
deceptive industry has grown up around these products, and we recommend they be
used only in a monitored program because they often simply don't work. Measuring
the IGF-1 level prior to commencing, and three months after starting a
secretagogue program will give you a much better idea of its benefit or lack
thereof. For more information on secretagogues, please visit that document:
http://www.888younger.com/abstracts/abs3.html
PREPARATIONS OF GrowthHormone
Although GrowthHormones is still under patent, several companies have paid
royalties to the original developers of HumanGrowthHormone for the rights to
manufacture and sell it. There are therefore a large number of companies now
manufacturing and distributing GrowthHormone worldwide. Those available in the
United States are, by brand name and the manufacturer's name:
Another option to the use of GrowthHormone is the use of GrowthHormone
releasing Hormone (GHRH) now manufactured only by Serono Laboratories and
branded Geref. GHRH works by stimulating our pituitary to make our GrowthHormone. This seems a more natural and rational approach because we are
stimulating the endocrine axis at a higher level, and increasing levels of
GrowthHormone more naturally. We don't prefer GHRH however, because we find it
more difficult to achieve adequate levels of IGF-1, and it is a bit more
expensive.
SUMMARY
Originally taken only from Human cadavers, and used only in children of short
stature, GrowthHormone 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 GrowthHormone deficient adults and aging adults. Because of the
tremendous similarities, GrowthHormone began to be used and soon gained great
popularity in the treatment of normal aging. GrowthHormone is clearly useful
and therapeutic in this regard as long as it is used in a carefully monitored,
professionally managed program. Any GrowthHormone program must include proper
nutrition and exercise with emphasis on a low glycemic diet.
