Introduction
The parenteral administration of human growth hormone (HGH) has
become an intervention of great significance in anti-aging medicine.
There is now frenetic interest in using reliable GH secretagogues in the
form of peptides, such as GHRP-2. Although age-related sarcopenia is
related to HGH deficiency, the use of HGH for the building of "lean
body mass" has been questioned, especially in young adults. Growth
hormone administration has precipitated ethical concerns and
controversies concerning its use in medical practice. There are many
Food and Drug Administration (FDA)-approved brands of HGH, and their use
is governed by federal law that has been in place for approximately two
decades. In brief, criminal use of HGH involves anyone who
"knowingly distributes or possesses with the intent to distribute
human growth hormone for any use in humans other than the treatment of a
disease or other recognized medical condition where such use has been
authorized by the Secretary of Health and Human Services (i.e., FDA) and
pursuant to the order of a physician" (21 USC s33 [e]).
The consequences of violating these laws that govern HGH use may
involve imprisonment for a period of up to five years (or longer). State
licensing authorities have taken disciplinary action (with irrevocable
license suspension) against physicians who have used HGH in a
"non-approved" manner. In these instances, the prescribing of
HGH has most often been for cosmetic or "body building"
initiatives and, in some cases, "anti-aging practices."
Adverse consequences of deviation from laws that govern the use of HGH
have gone beyond federal or state criminal prosecution to allegations of
malpractice with attendant civil liability. While some physicians have
argued that their use of HGH is quite legitimate, "anti-aging
therapy" has not been considered a valid use of HGH, according to
US law.
While arguments prevail about legitimate indications for the use of
HGH injections, credible bodies of opinion reject the common practice of
testing for insulin growth factor (IGF-1) levels as an adequate basis
for the diagnosis of growth hormone deficiencies. The diagnostic
criteria accepted for the presence of growth hormone deficiency involve
the demonstration of a subnormal response to GH stimulation tests (peak
GH
In brief, there are many disincentives to use GH injections in any
clinical context, other than those that have been defined as clearly
acceptable or perceived by regulators as part of "usual and
customary medical care." The putative side effect profile of GH
administration and an incomplete understanding of the safety and
effectiveness of prolonged administration of GH have pushed many
practitioners of anti-aging medicine to seek alternative options for the
regulation of HGH. It is against this background that practitioners of
Integrative Medicine are evaluating the use of GH secretagogue technology, as a potentially viable alternative to HGH injection
therapies.
Growth Hormone Release
Many stimuli promote GH secretion, but most act by neural
mechanisms. (1) Several centers in the brain control growth hormone
release, including the limbic system, the arcuate nucleus, and the
ventromedial nucleus (Table 1). These controls recruit different
neurotransmitters. (1), (2) These central nervous system (CNS) controls
result in the elaboration of growth hormone releasing hormones (GHRH),
which act on the anterior pituitary to release GH. Somatostatin can
inhibit GH release.
Control of GH secretion is quite complex and still not completely
understood. Factors such as stress, exercise, and protein depletion
release GH, whereas circumstances such as obesity, corticosteroid
administration, progesterone, and elevated levels of free fatty acids
inhibit GH release (Table 1). Glucose plays a special role in
controlling GH secretion. If GHRH peptides are administered with
glucose, the GH release is attenuated as a consequence of high blood
sugar promoting somatostatin secretion.
Table 1: A Simplified Overview of Factors that Release or Inhibit HGH
Secretion, by Anatomic Region
(Adapted from Merimee TJ, Grant MB. Growth hormone and its disorders.
In: Principles and Practice of Endocrinology and Metabolism. 2nd
edition. Philadelphia: JB Lippincott Company; 1995).
BRAIN
VENTROMEDIAL ARCUATE NUCLEUS LIMBIC SYSTEM Inhibition
NUCLEUS Inhibition by by unknown actions on
Inhibition by drugs, e.g., hippocampus/amygdala.
hyperglycemia, chlorpromazine Stimulation in deeper
beta adrenergic and other major stages of sleep or as
activity, tranquilizers. a consequence of pyrogens.
stimulation by Stimulation by
arginine or other dopaminergic
amino acids, activity.
glucagon, Neurotransmitter
hypoglycemia, and is dopamine or
vasopressin. clonidine.
Neurotransmitter is
norepinephrine.
OTHER
PITUITARY MISCELLANEOUS
Stimulation by Stimulation by exercise, stress, malnutrition,
GHRH and fasting, protein depletion, estrogenic stimuli.
inhibition by Inhibition by increased free fatty acids,
somatostatin. progesterone analogues, and corticosteroids.
GHRH is the
secretagogue with
the influence of
other chemical
messengers, e.g.,
metakenphalin
analogues, GHRP-2,
eicosanoids, or
prostaglandins.
There is a family of peptides that cause growth hormone release
(CHRP). These peptides are chemically related to met-enkephalin. (3-6)
Chemical modifications to several GHRP molecules have resulted in
increased GH-releasing potency. The most effective GHRP has been
identified as GHRP-2. (5-10) Of great interest is the ability to use
GHRP-2 in a non-invasive manner by oral or intranasal routes. (11-13)
perhaps providing a way of increasing GH levels by obviating the need
for HGH injections in some circumstances.
Aging in humans is associated invariably with decreases in activity
of the functional axis involving GH and IGF-1. (14-16) Overall, there is
a tendency for GH levels to fall with age, and patterns of GH secretion
show reduced frequency and amount of GH secretion. There is
approximately a 10-15% fall in growth hormone levels or actions in each
decade of advancing age (Figure 1). This results in a circumstance where
an individual in the seventh or eighth decade of life may have
approximately only five percent of the HGH that was present during
youth. Such reductions in GH secretion are notable in the presence of
insulin resistance (Metabolic Syndrome X) and obesity. (17-21)
[FIGURE 1 OMITTED]
The decline in the actions of growth hormone that is noted with age
has been identified as contributing to reduced musculoskeletal mass,
obesity, and reductions in cognitive function in the elderly. (21), (22)
The amino acid L-arginine--and other amino acids used in
combination--promote GHRH-stimulated GH release, (23) and amino acids
have been used as secretagogues in several dietary supplements, but
their effects may not be as potent or predictable as the use of a GHRP,
such as GHRP-2. (23), (24) Exercise can have major effects on blood GH
levels, and anaerobic exercise promotes GH secretion. Factors that
promote growth hormone release or its inhibition are summarized in Table
1, by reference to principle anatomic regions that are involved.
There are major gender differences in the controls of GH release.
(25) Women tend to have higher concentrations of GH compared with
age-matched men. It would appear that estrogen plays a role in
increasing the sensitivity of GH-releasing mechanisms to the many
stimuli that promote growth hormone secretion. These circumstances lead
to the strong inference that women in the post-menopausal transition of
life may have compromise of GH secretion, secondary to lack of estrogen.
Anti-aging physicians are increasingly applying GH with sex hormone
replacement therapy.
Investigation of the GH/IGF-1 Axis
Conventional medicine does not recognize the need for routine
screening for HGH deficiency in adults because of the fixed notion that
HGH therapy has discreet and finite indications. Integrative Medicine
often takes a different perspective with an increasing belief that
growth hormone has great therapeutic potential as an anti-aging or
"metabolic-enhancing" strategy. This notion is supported by
landmark studies that imply that GH replacement therapy in adults in
beneficial effects on abnormalities in body composition and physical
performance that are often encountered with increasing age. (27), (2 cool
Some studies have implied that HGH replacement beyond the
boundaries of conventional application has the disadvantage of potential
adverse outcome that is not balanced by therapeutic benefit, but
argument prevail. (27-29) While it is accepted that normal blood levels
of IGF-1 are reasonable indicators of adequate activity of HGH, low
levels of IG-F are not reliable predictors of HGH deficiency in humans.
It is peptides for sale important to reiterate that the "gold standard" of
diagnosis for GH deficiency involves use of one or more provocation
tests with measurements of growth hormone responses. In the practice of
anti-aging medicine, some physicians may fail to recognize the effect
that hypothyroidism or suppression of adrenal function may have on
growth hormone responses. The same reasoning applies often to sex
hormone deficiencies in the "integrative" medical mode of
care.
Two provocative types or categories of testing are applied most
often. One involves the induction of hypoglycemia with insulin followed
by subsequent measurements of GH release. The other categories of
testing may utilize GH-releasing peptides (GHRP-2), infusions of
arginine, administration of L-Dopa, sleep, vigorous exercise, or
clonidine administration. While these latter types of provocative
testing for growth hormone release are safer than insulin tolerance
tests, the results of such testing may be less accurate for the
diagnosis of HGH insufficiency. Unfortunately, no single test that
measures GH release to provocative stimulus is completely accurate, and
endocrinologists may apply more than one type of provocative testing
before they accept a "cast-iron diagnosis" of HGH deficiency.
The interpretation of these provocative types of testing may vary among
physicians.
The diagnostic dilemmas that are present in states of variable GH
deficiency are worthy of significant discussion. These circumstances
reinforce the complexity of the interplay of factors that control HGH
secretion. It appears that intermittent secretion of somatostatin exerts
major inhibitory effects on the output of HGH, and even the diagnostic
accuracy of provocative testing with GHRH peptides (GHRP-2) is perceived
to be inconsistent in its results. It is important to note that
provocative testing cannot uncover minor degrees of dysregulation of GH
release. This has led to a proposal for even more detailed assessments
such as the use of 24-hour integrated GH secretory responses that
require serial blood sampling over a 24-hour period. Arguably, there are
no attorneys or practice regulatory that can interpret GH provocative
testing results better than an experienced physician, and all laboratory
tests must be interpreted in the clinical context of the presentation of
the patient.
Actions of Growth Hormone
The major end-product of GH administration is the stimulation of
the production of IGH-1 or IGF-2, mainly in the liver. The GH/IFG-1 axis
is responsible for stimulation of body growth, and it exerts major
effects on body metabolism. Overall, the physiological effects of GH are
biphasic. The acute administration of GH exerts insulin-like effects
where there are notable increases in glucose uptake in muscle and
adipose tissue, with concomitant stimulation of amino acid uptake and
protein synthesis in muscles and the liver, A major acute response to GH
injections is lipolysis, but a number of hours after the administration
of HGH, these metabolic effects cease and more complex biochemical
events occur in the body.
In these secondary phases of response to GH, GH activity becomes
antagonistic to the actions of insulin, with inhibition of glucose
uptake, resulting in hyperglycemia and increased lipolysis. This results
in an elevation of circulating free fatty acids. Fasting induces a rise
in blood levels of HGH, and this adaptation is a response to acute
starvation. In this regard, HGH works in concert with other hormones
that cause a rise in blood glucose (epinephrine, glucagon, and cortisol)
to support the availability of CNS function (an adaptation response in
the harmony of life). In addition, GH tends to diminish fat stores to
provide alternative energy sources for the body, especially during
periods of fasting.
The actions of HGH are complex. Some studies imply that HGH has
effects independent of IGH-1 and IGH-2 production (old nomenclature in
the US: somatomedin C, etc. or growth stimulating end-products). (30-33)
Some studies imply that adipocytes and chondrocytes may show increased
responsiveness to IGH after initial exposure to GH, and certain
metabolic responses in renal tubular epithelium occur as a consequence
of GH stimulation in a manner that is not observed in the presence of
IGH-1 or IGF-2 in high concentrations. (30-33)
While several theoretical "risks" are proposed with
prolonged HGH administration, the proponents of GH replacement therapy
describe few substantial side effects. The adverse effects of chronic GH
administration are most often related to fluid retention, which occurs
in an intermittent, dose-dependent circumstance. (28-3 cool However, the
antagonistic actions of GH on insulin actions and the potential
promotion of the growth of cancer or cellular proliferation (a function
of growth factors) present serious, residual concerns. It would appear
that the chronic administration of high dosages of GH in some
individuals has resulted in a clinical syndrome that is substantially
similar to acromegaly. Such observations have been reported, often in an
anecdotal manner, in the extreme aerobic enthusiast or "elite
athlete" who may develop a form of "dependence" on their
perceived need for body contouring to achieve their
"aesthetic" ambitions. Mixed abuse of anabolic steroids with
GH in some body-building enthusiasts clouds the clinical picture
("Droid Boys and Girls" wink .
While growth hormone is diabetagenic overall, it is worrisome that
insulin-like growth factors are potent mitogens and proliferative
factors for several cell types. Including breast, colon, and prostate
epithelial cells. Anti-aging physicians have tended to reject these
concerns, but well-constructed clinical trials show a relationship
between IGH-1 levels and the promotion of breast or prostate cancer.
Increased values of IGH-1 have been associated with an increased risk of
prostate cancer (and perhaps benign prostatic hyperplasia) in two
studies. (39-40) The relationship between IGH-1 and breast cancer is
somewhat conflicting, but in vitro studies show that IGH-1 is a potent
stimulator of cell division in breast cancer cell lines. In a
Scandinavian study of premenopausal women with elevated levels of IGH-1
a significant correlation was observed between increased IGH-1 levels
and breast cancer. (41) The potential association of chronic GH
administration with persistent high levels of IGH-1 had led to proposals
that frequent monitoring of free testosterone levels, blood PSA levels,
estrogen levels, and mammography is required variably to assess risks of
cancer development in men or women who are receiving GH therapies.
Adult GH Deficiency Syndromes
There have been attempts to define symptoms and signs that permit
the recognition of "adult HGH deficiency," and it has been
argued strongly that there is approval to treat this syndrome in general
medical practice, provided that this syndrome is documented with
provocative testing of GH secretion (perhaps using two different
provocative testing methods?). Other bona-fide recommendations for GH
therapy include Turner's Syndrome and body wasting due to AIDS. In
brief, symptoms and signs that are attributable to adult HGH deficiency
include prominent wrinkling of the skin, sagging cheeks and neck
tissues, hair loss with thinning of lips and facial bones,
pseudogynaecomastica, pot belly, sarcopenia, fatigue, and behavioral
chang. Unfortunately, this constellation of symptoms and signs is quite
non-specific, but coexisting laboratory abnormalities may include
reduced IGH levels, abnormal blood cholesterol, impaired thyroid
function, high fibrinogen, and raised blood levels of osteocalcin.
Descriptions of adult GH deficiency syndrome seem to bear
substantial resemblance to symptoms and signs that are encountered in
Metabolic Syndrome X, (42) where a major conundrum exists. In Syndrome
X, there is a relationship between hyperinsulinemia and cancer that may
be best explained by the growth-promoting effects of IGF-1. (42)
Therefore, I recommend strongly that individuals with Metabolic Syndrome
X be identified and treated for their specific constellation of
problems, before clinical plans move towards GH "replacement
therapy." This circumstance is an under-explored area of clinical
practice, but the clinician must understand that the prevalence of
Metabolic Syndrome X is much higher than that of adult GH deficiency. It
is estimated that up to 70 million Americans have the Metabolic Syndrome
X. (4) The diatheses of the Metabolic Syndrome X and adult GH deficiency
may often co-exist, and they are both strongly associated with the
development of atherosclerosis and increased cardiovascular disability
or mortality and other causes of premature death and disability.
(34-3 cool , (42)
There are many compelling studies that imply beneficial effects of
GH treatments in aging individuals. (43) Demonstrated GH deficiency that
remains untreated in adults is clearly associated with abnormal body
composition, decreased extracellular water and bone mineral content, and
enhanced cardiovascular disease and mortality. (2) This body of medical
literature has prompted several popular, well-written accounts of the
use of growth hormone in anti-aging medicine. (34-3 cool In brief, the
clinical benefits associated with increasing HGH levels in the presence
of HGH deficiency in adults are summarized in Table 2, which is adapted
from the popular work of R. Klatz, R. Goldman, and C Kahn. (34), (35)
Table 2: Many Actions of GH Replacement Therapy Have Been Described in
Popular Literature.
These data are based upon positive interpretations of peer-reviewed
medical literature.
Data has been presented in many formats, as found in references 34-37.
Potential Positive Actions Associated with Increases in HGH Levels
in States of GH Deficiency.
* Enhanced muscle mass (>8% * Improvement in blood cholesterol
after six months) (increased HDL, reduced LDL)
* Decreased body fat (>14% * Improved bone strength
after six months)
* Increased energy level * Increased rapidity of wound healing
* Enhanced sexual performance * Regrowth in thinning hair or hair loss
* Reversal of age-related * Wrinkle reduction
shrinkage of certain organs
(heart, liver, spleen,
kidneys, thymus, etc.)
* Greater cardiac output. * Cellulite reduction
* Enhanced immune function * Improved vision
* Improvement in kidney * Elevation of mood
function
* Enhanced exercise * Improved cognitive function and memory
performance
* Blood pressure reduction * Enhanced sleep
Is HGH Parenteral Therapy an Acceptable Anti Aging Strategy?
In a review, published in the Annals of Internal Medicine in 2007,
(29) the safety and efficacy of GH therapy in healthy individuals was
examined. This review concluded that HGH injections may not be
cost-effective or beneficial in routine anti-aging clinical practice.
The conclusions were based largely upon meta-analysis studies, but such
statistical manipulations of compiled data are notoriously difficult in
their ability to reach portable conclusions. The selection of studies
that are "thrown into the statistical mix" in a meta-analysis
study exerts a major influence on the reported outcomes.
In the aforementioned negative systematic review (29) of GH use, it
appears that a large proportion of the selected studies involved the
investigation of patients who had received either large dosages of HGH
or poorly described dosage schedules. Dosages of HGH used in the
treatment of dwarfism or Turner's Syndrome tend to be large because
the desired clinical outcome is significant growth and enhanced stature
from bone elongation. These dosage regimens of HGH are much higher than
those used in routine anti-aging practice, where many physicians use
more modest dosages of HGH of the order of 1-2.5 IU. In fact,
dose-response information on the treatment of adult GH deficiency is not
readily available, and it has not been fully researched.
General consensus would support initial dosage in correction of
adult GH deficiency to be up to 0.9 IU per day with gradual increases in
dosage at approximate monthly intervals to achieve the required outcome,
which must be closely monitored. It appears that dose requirements for
GHG decline with age, and maintenance dosage of GH injections, in this
context, require approximately 3 IU per day, or less. Most physicians
agree that measurements of blood IGF-1 are useful as guidance for the
titration of the administered dosage of GHG, but careful clinical
monitoring is or great importance. The adverse clinical outcome of HGH
administration, noted in the systematic review, (29) included edema,
joint discomfort, and abnormal glucose tolerance tests, but there is
some suggestion that such side effects are not encountered with any
frequency at lower dosages of GH that are currently used in anti-aging
medicine.
There have been some allegations that negative reporting about the
use of anti-aging interventions with HGH is fueled by individuals with
vested interests. Clearly, our current level of scientific knowledge
still casts some degree of doubt on the routine acceptance of HGH
therapy as a cost/effective anti-aging strategy, with an acceptable
risk/benefit. These debates continue.
Reviewing HGH Secretagogues
Several nutritional formulae have been proposed as dietary
supplements to stimulate the release of HGH and the consequential
production of IGF-1. Several of these formulae have been proposed as
effective, cost-advantageous ways of stimulating GH release. They have
been proposed as an alternative to parenteral GH administration, which
may cost up to 50,000 USD per year. (34), (37) These formulae most often
use amino acids in variable combinations to promote GH release. Selected
amino acids or chemical secretagogues include L-arginine, L-lysine,
L-glutamine, L-ornithine, L-dopa, GABA, glycine, etc. There is some
suggestion that combinations of amino acids are more effective than the
use of single amino acids alone, but there is major inter-and
intra-individual variation in GH secretagogues responses. (34), (35),
(37)
Dosages of the order of 15-20 grams per day or more of mixed amino
acid formulations, taken over periods of several weeks, have been shown
to increase IGF-1 concentrations in small patient samples, in open-label
clinical studies. It has been suggested that effervescent powdered
formulations of amino acids are more effective than other formulations
(34), (3 cool but the evidence for these and other statements of advantage
remain unclear. Marketing organizations have suggested that putative
HGH-releasing formula should be given to any individual with an IGF-1
< 350ng/ml, but this would include the bulk of the populations over
the age of 40 years. (51) While research on dietary supplement formulae
of amino acids that may release GH is sparse, a significant body of
evidence exists that amino acids can effectively release growth hormone.
(52-55)
The most recent innovations in the use of dietary supplements to
stimulate GH secretion involve the use of GHRP, most notably GHRP-2. A
deficiency of GHRP peptides is one of several factors that have been
implicated in the reduction of GH secretion that has been documented in
elderly individuals. (56) Other factors that variably operate include a
reduction in the functional capacity of GH-secreting cells in the
pituitary, including a deficiency of the hormone ghrelin and increases
in somatostain secretion that have an inhibitory effect on GH release.
A large body of evidence has accrued that GHRP-2 is a highly
effective way of increasing GH levels in many individuals. (11), (56-62)
Peptides that release GH belong to a family of synthetic chemicals that
have a polypeptide sequence of five to seven amino acids. Such peptides
were originally synthesized as copies of metenkephalin peptides. A
number of laboratory and clinical studies imply that these peptides act
on both the pituitary and hypothalamus, but GHRP-2 binds to pituitary
receptors that are quite separate from opiate receptors and
GHRP-receptors. (63-69)
It is important to note that stimulation of GH release in elderly
individuals may result in levels of GH that are encountered in young
adults. (23) Furthermore, the administration of GHRP-2 in combination
with GHRP or L-arginine can result in substantial increases in GH
levels. (23) The hormone ghrelin may play a major role as a GH
secretagogues, and increases in blood levels of the orexigenic hormone
ghrelin are sometimes noted in individuals with sleep deprivation. This
is a contrarian observation, because deep sleep is associated with
stimulation of GH secretion. Again, the complexities of GH secretion and
the actions of GH appear repeatedly in scientific literature.
It is noted that GHRPs have greater GH-releasing actions than GHRP,
and GHRP-2 can be administered by oral or intranasal routes with
evidence of GH-releasing actions of a significant magnitude. (55-62) It
is proposed that GHRPs, most notably GHRP-2, are able to be made
available as dietary supplements. (70) In order for this position to be
tenable, GHRPs should have been available in the food chain prior to
1994 with some precedent of use for a health benefit (to conform to the
US Dietary Supplement and Health Education Act of 1994). In fact, GHRPs
have been arguably present in the food chain, but GHRP-2 is a synthetic
molecule. However, there are several dietary supplements that are
synthetic molecules that have gained acceptance as dietary supplements,
e.g., ipriflavone, which occurs only in very small quantities in the
food chain. Obviously, these circumstances are not completely clear, but
manufacturers of GHRP-2 have taken the position that they can sell
releasing peptides as dietary supplements, but they have preferred to
limit their dispensation through health care givers. (70)
There is no doubt whatsoever that oral GHRP-2 can be expected to be
effective in releasing growth hormone in humans, with some degree of
variable response. (56-69) The use of these potent secretagogues has
become very popular in recent times, and good clinical outcome has been
described among anti-aging physicians in a national forum (71) A major
advantage has been perceived with the use of secretagogues for the
promotion of GH release, because there is a reliance on the pituitary to
perform its usual and customary function. Some physicians have suggested
that this approach is more natural than attempts to titrate growth
hormone injections in anti-aging treatment protocols. In other words,
the use of GH releasers fit with body homeostatic mechanisms, in
comparison with HGH injection therapy. However, long-tern outcome of the
administration of GH secretagogues remains under-explored, in the same
way that the long-tern administration of GH injections in adult GH
deficiency syndrome or elderly subjects remains a matter of incomplete
understanding.
Recommendations for Stated Anti-Aging Strategy
Protagonists of hormone replacement in anti-aging medicine conclude
that the optimization of hormonal status in the aging individual
requires careful supervision and expert application to achieve optimal
outcome. One expert in the field stated, "The first thing we should
remember is that we should not be rushing to throw hormones at people.
Hormone optimization is the finishing touch. "(72) The author
echoes these comments strongly and considers hormone therapy to be
"icing on the cake of anti-aging medicine. " In the July of
2008 Townsend Letter, (73) the author provided a review of a
bio-integrative approach to anti-aging interventions that focused on the
role of holistic care as the first-line option for anti-aging. The
author of this article has rejected the notion that there are "true
bioidentical hormones," but he does accept notion of bio-similarity
with its putative enhancement of safety (and perhaps efficacy?). That
said, recent information seems to indicate that the timing of the
administration of certain hormone supplements in the chronology of
altered body composition with age, especially sex hormones, may be quite
critical in overall clinical outcome in anti-aging medicine. (72), (74)
I must sound the warning that all clinicians who recommend hormone
replacements must educate themselves in the legal considerations that
govern the use of controlled hormone substances, including GH and sex
hormones. (75), (76) An excellent summary of legalities in hormone use
are to be found in the recent presentations of Risk Collins, Esq. (75),
(76)
Conclusion
There seems to be a good reason to reappraise how GH deficiency can
be approached in clinical practice. If regulations permit the use of
releasing peptides or secretagogues, as seems to be the case at this
juncture, then arguably this approach represents the first-line option
in attempts to increase GH levels in those individuals with documented
deficiency of GH. Clearly, a number of issues remain unresolved, but the
use of GH in anti-aging medicine has become established on a global
basis, despite continuing controversies concerning its safety,
effectiveness, and widespread availability. It seems quite problematic
that the use of GH appears to be legislated in a manner that removes a
physician's judgment as to whether or not to apply this type of
intervention, but there is an increasing consumer demand for freedom of
choice in health care; many people are requesting GH therapy as an
anti-aging tactic.
Notes
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revisited: spontaneous versus stimulus-initiated tides. In: Pecile A,
Muller EE, eds. Growth and Growth Hormone. Amsterdam: Excerpta Medica;
1972:371.
(2.) Martin JB, Audet J, Saunders A. Effects of somatostain and
hypothalamic ventromedial lesions on growth hormone release induced by
morphine. Endocrinology. 1975;96:839.
(3.) Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and
in vivo activity of a new synthetic hexapeptide that acts on the
pituitary to specifically release GH. Endocrinology. 1984;114:1537-1545.
(4.) Bowers CY, Sartor AD, Reynolds GA, Badger TM. On the actions
of the growth hormone-releasing hexapeptide, GHRP. Endocrinology.
1991;128:2027-2035.
(5.) Bowers CY. GH releasing peptide-structures and kinetics. J
Pediatr Endocrinol. 1993;6:21-31.
(6.) Bowers CY, Veeraragavan K, Sethumadhaven. Atypical growth
hormone releasing peptides. In: Bercu BB, Walker RF, eds. Growth Hormone
II, Basic and Clinical Aspects. Berlin: Springer-Verlag; 1994:203-222.
(7.) Mericq V, Cassorla F, Garcia H, Avila A, Bowers CY, Merriam
GR. GH responses to GHRP and to GHRH in GH deficient children. J Clin
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(8.) DeBell WK, Pezzoli SS, Thorner MO. GH secretion during
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(9.) Bowers CY, Alster DK, Frentz JM. The growth hormone releasing
activity of synthetic hexapeptide in normal men and short statured
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(10.) Bercu BB, Yang S, Masuda R, Walker RF. Role of selected
endogenous peptides in GHRP activity: Analysis of GHRH, thyroid
hormone-releasing hormone, and gonadotropin-releasing hormone.
Endocrinology. 1992;130:2579-2586.
(11.) Pihoker C, Kearns GL, French D, Bowers CY. Pharmacokinetics
and pharmacodynamics of growth hormone-releasing peptide-2: A phase I
study in children. J Clin Endocrinol Metab. 1998;83(4):1168-1172.
(12.) Mericq V, Cassorla F, Salazar T, et al. Increased growth
velocity during prolonged GHRP-2 administration to GH deficient children
(Abstract). Proc of the 77th Annual Meet of The Endocrine Soc. 1995;85.
(13.) Laron Z, Frenkl J, Eshet R, Klinger B, Silbergeld A. Human GH
and insulin-like growth factor-1 stimulating and growth promoting
effects by long term intranasal administration of the
hexapeptide-hexarelin (Abstract). Proc of the 77th Annual Meet of the
Endocrine Soc. 1995;504.
(14.) Corpas E, Harman SM, Blackman MR. Human growth hormone and
human aging. Endocr Rev. 1993;14:20-39.
(15.) Harris TB, Kiel D, Roubenoff R, et al. Association of
insulin-like growth factor-1 with body composition, weight history, and
past health behaviors in the very old: The Framingham Heart Study. J Am
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Stephen Holt, MD, is a clinician, researcher, and best-selling
author. He is a Knight of Grace of the Holy Order of St. John and the
recipient of many honors and awards for medical teaching and research.
He is a scientific advisor to Natural Clinician LLC, Little Falls, NJ, a
company that sells health care products. Dr. Holt is regarded as a
pioneer of Integrative Medicine, and he is the President of the World
Organization of Natural Medical Practitioners (www.wonmp.us).
[ILLUSTRATION OMITTED]
* Stephen Holt, MD, LLD (Hon.) ChB., phD, ND, FRCP (C), MRCP (UK),
FACP, FACG, FACN, FACAM, KSJ, Distinguished Professor of Medicine,
Chairman, New York Dept. of Integrative Medicine, NYCPM, Lieutenant
Grand Hospitaller, Holy Order of St. John
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