Anti-Aging Therapeutics, volume 6, Chapter 3, 2004
American Academy of Anti-Aging
Medicine
Is Growth Hormone Replacement for
Normal Aging Safe?: Analysis of
Current Medical Literature
Ronald Rothenberg, M.D,
Clinical Professor, Preventive
& Family Medicine,
University of California San
Diego (UCSD) School of Medicine:
Founder, California HealthSpan
Institute
ABSTRACT
The purpose of this paper is to discuss whether or not
growth hormone replacement therapy (GHRT) for the
treatment of somatopause of normal aging is safe and
effective. In order to determine this it is important
to learn about growth hormone (GH), the benefits of
GHRT, and its side effects. We will also discuss
whether or not pathological GH deficiency is the same
as GH deficiency caused by "normal aging." The links
between GHRT and cancer and insulin resistance are
also debated.
Keywords: growth hormone; growth
hormone replacement theory; growth hormone deficiency;
inflammation
INTRODUCTION
The purpose of this paper is to discuss whether or not
growth hormone replacement therapy (GHRT) for the
treatment of somatopause of normal aging is safe and
effective. This paper is not going to deal with the
basics of GHRT, i.e doses and optimal delivery
techniques. Instead it will address the following
important questions:
-
What are the benefits
of GHRT
-
Is "Normal Aging" GH
deficiency the same as "Pathological" GH deficiency
-
Does GHRT increase the
risk of cancer
-
Does GHRT cause
insulin resistanc
-
Are the possible side
effects of GHRT manageable nuisances or serious
problems
GROWTH HORMONE, SOMATOPAUSE, AND AGING
Growth hormone (GH)
exerts a variety of physiological effects on the body.
Endogenous peptide ligands such as ghrelin, growth
hormone releasing hormone (GHRH), and growth hormone
releasing peptide (GHRP) all stimulate the interior
pituitary to release GH. GH migrates to the liver to
produce insulin-like growth factor 1 (IGF-1). Sixty
percent (60%) of the effects that GH has on the body
are exerted via IGF-1. For example, GH's anabolic
effect upon muscle, bone, and cartilage, and its
lipolytic effect on fat, are all mediated by IGF-1. GH
and IGF-1 can both pass through the blood-brain
barrier.
Somatopause signifies
the gradual decline in growth hormone production by
the pituitary gland. Somatopause can begin anywhere
between the ages of 35 and 50, however when it does
occur a person's GH levels will drop significantly. In
an article published in Hormone Research in 2000,
Savine et al concluded that life without growth
hormone is poor both in quantity and quality. The
emphasis here should be placed on quality as
maintaining a good quality of life is the goal. Savine
found that GH peaks at puberty and starts decreasing
at 21. At the age of 60, most adults have the same
24-hour secretion rate indistinguishable from those
hypopituitary patients with organic lesions in the
pituitary gland. Thus, a normal 60-year old is the
same as a sick 25-year old in terms of GH levels.
Savine also concluded that if an IGF-1 level of 300 is
mean normal for a 20 to 30-year old, almost everybody
over the age of 40 has an IGF-1 deficit.
However, what does GH
have to do with aging? The important factor here is
inflammation. Chronic inflammation is the cause of
many age-related diseases. Thus doing whatever we can
to decrease chronic inflammation is important in the
quest to stay healthy. A number of things can be done
to help combat inflammation. For example: keeping
glucose and insulin levels under control, taking
regular exercise, and eliminating the visceral
abdominal fat. Abdominal fat is a living, throbbing
endocrine organ that produces inflammatory cytokines,
like IL-6. So carrying extra fat is not just a
cosmetic issue. By eliminating visceral abdominal fat
the person is also getting rid of a very dangerous
inflammatory-producing organ. It is also possible to
lower inflammation by controlling the Omega-3 to
Omega-6 ratio and eliminating infections: most health
professionals are now aware of the connection between
heart disease and periodontal disease and chlamydia.
Another way of combating inflammation is stress
reduction, as stress produces inflammatory cytokines.
Control of the free radicals, homocysteine levels,
advanced glycation end products, and youthful
hormones, such as testosterone, estrogens, growth
hormone, and IGF-1 all decrease these inflammatory
cytokines. Inflammation induces GH insensitivity,
however GHRT decreases inflammation. Thus, reducing
inflammation also improves the body's sensitivity to
GH.
We know that a person's
C-Reactive Protein (CRP) levels are the strongest
predictor of whether or not they are going to have a
myocardial infarction or not. CRP is far superior to
LDL-cholesterol. Thus, it makes sense to keep CRP
levels as low as possible. Where does CRP come from?
Interlenkin-6 (IL-6) tells the liver to produce CRP.
So to keep CRP under control, IL-6 levels also need to
be kept at a minimum. Homocysteine raises
inflammation, therefore it needs to be kept low. Too
much insulin induces inflammation as does tumor
necrosis factor-a (TNF-a), as does interleukin-10
(IL-10): these are all things that need to be kept
under control. Inflammation is linked to many chronic
illnesses, from heart disease, to syndrome X, to
dementia, to depression, cancer, osteoporosis, and
autoimmune disease: all have high inflammatory
mediators. Maybe the question should be: "Why are we
so inflammatory?"
Insulin resistance
provides us with a good analogy for understanding why
the body is prone to inflammation. Insulin resistance
was a good thing for our Paleolithic ancestors. If you
could store fat and make it through famine, you would
live long enough to pass on your DNA. No one lived
long enough to develop Type II diabetes and its
numerous complications, so that was not a problem. It
is the same thing with inflammation. If a person's
body is geared towards making inflammatory cytokines,
they will get by when a saber tooth tiger bites them.
White cells will rush to the infection and their blood
will clot. Being prone to inflammation is a bonus when
faced with acute trauma and acute infectious disease.
As these two things were the main challenge to our
ancestors, it is in the genome. We have evolved to be
prone to inflammation. Now, since trauma and infection
are not such a great threat to most people, and now
that we are living significantly longer lives, this
inflammatory state is killing us. Just as the insulin
resistance is killing us.
Moving back to the
original question of GH and aging. We age because our
hormones decline, not the other way around GH is vital
in order to live a healthy adult life. Why? GHRT
improves quality of life. What other benefits does
GHRT have? GHRT is beneficial to the brain, the
cardiovascular system, the immune system, aerobic
capacity, body composition, and bone.
It is interesting to
compare the viewpoints anti-aging specialists and
conventional endocrinologists have on GH. Both groups
agree that pathological GH deficiency is a disease
that should be treated. Both groups agree that GH
secretion declines with age, and both groups agree
that GH decline is responsible for part of the
clinical syndrome of aging. This is where anti-aging
and endocrinology's agreement on GH ends. Anti-aging
specialists believe that aging and GH decline is a
deficiency disease, which can and should be treated.
But the vast majority, if not all, of endocrinologists
believe that aging and GH decline are normal and
should not be treated.
Cappola et al carried
out a study to investigate what factors were
associated with a better quality of life in women aged
70 and over. The results showed that women who had the
best quality of life in terms of functional capability
(that is walking limitation, mobility, activities of
daily living, cognition and so on) had high IGF-1
levels and low IL-6. Thus they had high GH levels and
minimal inflammation. The concept is that decreased GH
levels and decreased IGF-1 levels lead to frailty.
Somatopause is the entry into frailty.
So, does GHRT provide us
with the long searched for fountain of youth? No, it
does not. But we are on a programmed course of
destruction and GHRT could help slow it down a little
and improve our quality of life. If the benefits
outweigh the risks, then something is worth doing.
GHRT is a work in progress. It may not be perfect, but
it is the best we have at present.
BENEFITS OF GROWTH HORMONE
Growth Hormone and the Brain
GH deficiency is associated with neurocognitive
decline, and GHRT improves memory, alertness, and
concentration. It is quite amazing that GH can pass
through the blood brain barrier, as it is a very large
molecule made up from 191 amino acids. The brain needs
GH and it needs IGF-1. Many people think that GH is
good, whereas IGF-1 is bad, and that we want to
increase GH without increasing IGF-1. That is not the
case. More than half of the action of GH is exerted
through IGF-1, and the general consensus is that both
are necessary. So growth hormone improves cognitive
capabilities, memory, motivation, and work capacity.
There are GH-receptors situated all over the brain.
Aleman et al correlated IGF-1 with cognitive function
in men, with higher IGF-1 levels being linked to
better cognitive function. GH deficiency was
correlated with poor emotional and psychosocial
functioning.
Growth Hormone and Bone
GH increases the strength and formation of cortical
bone. Logobardi linked GH deficiency with reduced bone
density, and GHRT with reversal of osteoporosis.
Patients who sustain hip fractures tend to have lower
IGF-1 levels. GH is synergistic with exercise, thus to
get the maximum effect from GHRT it has to be combined
with regular exercise. Van der Lely et al treated
patients over 75 with hip fractures with GH at the
time of fracture for six weeks. The end point was
return to pre-fracture living arrangements. Results of
the double-blind placebo-controlled trial showed that
94% of patients treated with GH returned to
pre-fracture living within just six weeks, compared
with the 75% of control patients.
GH increases bone
mineral density. Gillberg et al treated men with
idiopathic osteoporosis with GH. Participants were
randomly assigned to treatment with GH, either as
continuous treatment with daily injections of 0.4 mg
GH or as intermittent treatment with 0.8 mg GH for 14
days every 3 months. All patients were treated with GH
for 24 months, with a follow-up period of 12 months.
No positive effects of treatment were noted at the
12-month follow-up. But after 12 months there was a
continued increase in bone mineral density and no
significant adverse effects were reported. After two
years of GH treatment significant improvement in bone
mineral density were observed in both groups.
Growth Hormone and the Cardiovascular System
GH deficiency is associated with increased
cardiovascular mortality, while GHRT is associated
with improved cardiovascular function. Research
suggests that GHRT may help to reverse
atherosclerosis, improve cardiomyopathy, and reduce
carotid intima media thickness.
Pro-inflammatory
cytokines contribute to chronic and acute heart
failure. Adamopoulos et al treated patients with
idiopathic dilated cardiomyopathy (IDC) with GH.
Results showed that GH treatment led to a significant
decrease in both TNF-a and IL-6 levels, and
significant improvements in exercise capacity.
GH also corrects
endothelial dysfunction. Too much emphasis is placed
upon the cholesterol model of atherosclerosis.
Inflammation and endothelial dysfunction are very
important factors. Cholesterol may be present at the
scene of the crime, but it did not trigger the whole
process going. GH improves endothelial dysfunction,
which plays a significant role is both heart failure
and arteriosclerosis.
What about homocysteine?
We know that homocysteine is a strong predictor of
cardiovascular disease. Sesmilo et al randomly
assigned 40 men with GH deficiency to treatment with
GH or a placebo for a period of 18 months.
Homocysteine levels fell significantly in those
treated with GH.
What about CRP, which is
the strongest predictor of cardiovascular events that
we have? CRP is very high is GH deficiency. With GHRT,
CRP decreases and visceral and subcutaneous fat
decreases. As we know, visceral fat produces IL-6,
which is turn produces CRP.
Thus, the cardiovascular
improvements seen with GHRT, appears to be down to its
effect upon the inflammatory pathway. IGF-1 is a
cardiac hormone. It improves cardiac contractility,
stroke volume, and ejection fraction. It improves
insulin levels: intracardiac insulin levels, and
increases insulin sensitivity. So the heart needs
IGF-1. Certainly, after myocardial infarction, IGF-1
is critical in the remodeling of the heart ad
recovery.
Growth Hormone and the Immune System
When considering GH and the immune system we have to
look at the bigger picture, that is, we have to
consider the neuro-endocrine-immune system as all part
of one system. IGF-1 is vital for lymphocyte
maturation. It will restore age-related thymic
involution in rodents. IGF-1 is needed to develop
T-cells and B-cells, and the age-related decline in
these important cells can be reversed with GHRT.
Growth Hormone, Body Composition, and Obesity
It is a well-documented fact that GHRT can decrease
visceral abdominal fat, a cytyokine-producing organ,
by as much as 50%. According to Christiansen, GH
deficiency is linked to:
-
Abnormal body
composition
-
An increase in adipose
mass and decrease in muscle mass
-
Insulin resistance
-
Decreased muscle
strength
Long-term GHRT can normalize these abnormalities.
GH secretion is impaired
in obesity. Johannsson et al studied middle-aged men
with low GH and abdominal obesity. After nine months
of treatment with GH, abdominal visceral fat decreased
by 18%, insulin sensitivity improved, total
cholesterol, LDL, and triglyceride levels dropped, and
diastolic blood pressure decreased. The men did not
make any lifestyle changes during the study. An 18%
decrease in visceral abdominal fat without making any
lifestyle alterations is quite impressive.
Blackman et al studied
the effect of treating healthy men and women with sex
steroids and GH. The women received HRT, which was
Estraderm (transcutaneous estradiol), plus Provera:
this was not a wise choice, as Provera increases
insulin resistance. The men were given 100mg of
testosterone once every two weeks. One group of men
and women were treated with only sex steroids, while
another where also treated with GH at a fixed dose per
weight, which is not a good way to treat people with
GH in terms of producing side-effects Anyway, a fixed
dose was used and the patients where given GH three
times a week. Results showed that visceral abdominal
fat decreased by 14% in men treated with GH alone, and
16% in those given GH and testosterone. Interestingly,
women who were treated with GH alone did not lose
abdominal fat, but when GH was combined with HRT they
did. A second study by the same group was published a
year later in 2002. The participants were treated with
the same regimen as in the 2001 study. Lean body mass
increased in women treated with HRT and GH by an
average of 2.1 kg, and in men treated with
testosterone and GH by an average of 4.3 kg. Fat mass
decreased in both groups of men and women. V0 max
increased in both men and women, and muscle strength
increased by 6.8% in men treated with both GH and
testosterone. These changes occurred within six
months, and once again, the participants made no
life-style changes: imagine what results you may
achieve by implementing positive life-style changes.
However, not all the results were beneficial: 38% of
women suffered from edema; 32% of men treated with
both GH and testosterone suffered from carpal-tunnel
syndrome; and 41% of men treated with GH suffered from
arthralgias. Diabetes or glucose intolerance was noted
in 18 men treated with GH, compared with just 7 men
who were not treated with GH. Unfortunately, the press
picked up on the adverse effects reported by the
research team, and the resulting headlines read:
"Growth Hormone Replacement Therapy Causes Diabetes."
People who use GH in clinical practice know that this
is simply not true. In terms of insulin resistance, GH
can make it worse if the patient's life-style is not
managed correctly. If lifestyle is not managed
correctly insulin resistance could improve
dramatically. The very high rate of side-effects seen
with this study might be related to the dosage
schedule: the fixed dose per weight and the three
times a week; and not titrating the dose. This
side-effect profile is not seen in clinical practice.
In clinical practice, approximately 10% of patients
may suffer from such side-effects, however these are
manageable simply by decreasing the dose.
Other Benefits of Growth Hormone
Every study of GH and exercise capacity shows that GH
increases VO max. Gibney et al found a link between GH
deficiency and chronic fatigue and depression.
Meanwhile, GHRT was found to improve a person's sense
of well-being and was associated with an improved
quality of life. Gilchrist et al concluded that GH
deficient adults have a poor quality of life, but that
this poor quality of life could be altered with GHRT.
Gilchrist found that GHRT significantly improved
energy levels, vitality, anxiety, depression,
well-being, and self-control.
GROWTH HORMONE AND INCREASED MORTALITY IN PATIENTS IN
ICU
One study that is often brought up when people talk
about GH is a study by Takkala et al that was
published in the New England Journal of Medicine in
1999. In this study, critically ill patients: half of
whom were on ventilators, a lot of whom were suffering
with acute respiratory distress syndrome, were treated
with large doses of GH, 16 to 24 units per day. The
average anti-aging dose can very from 4 to 13 units a
week or 1 unit a day. The outcome was not good.
Significantly higher numbers of patients treated with
GH died. So we can conclude that an overdose of GH is
not good. A rebuttal to this study by Bengtsson et al
in the Journal of Clinical Endocrinology looked at a
meta-analysis of over 2,000 patient years, none of
which was associated with increase in mortality.
GROWTH HORMONE AND CANCER
Does GHRT increase the risk of cancer? Vance et al
concluded that there is "No evidence that GHRT affects
the risk of cancer or cardiovascular disease."
Meanwhile Molitch concluded: "Although there has been
some concern about an increased risk of cancer [with
GHRT], reviews of existing, well-maintained databases
of treated patients have shown this theoretical risk
to be nonexistent. " Shalet et al concluded that there
is "No evidence of an increased risk of malignancy,
recurrent or de novo." On the package insert on GH it
says don't use in active malignancy. However, the
Growth Hormone Research Society published a paper in
the Journal of Clinical Endocrinology saying that
there is no data to support this labeling, and that
current knowledge does not warrant additional warning
about cancer risk. They say that this line should be
removed from the package insert because there is no
evidence that GH increases cancer recurrence or de
novo cancer or leukemia.
When the issue of GH and
cancer is being discussed, the Chan study is always
referenced. Blood was drawn for IGF-1 and IGF binding
protein-3 (IGFBP-3), and other studies, on a group of
men. The blood was stored, and then 15 years later the
investigators followed-up the participants to see
which men developed prostate cancer. Men who had the
IGF levels in the highest quartile had the most
prostate cancer. There are some interesting aspects to
this study. Firstly, the blood was stored for 15
years. Secondly, the IGF levels in the highest
quartile were between 300 and 500. The average age of
men at the start of the study was 59. Now, it is
unlikely people in clinical practice will ever have
seen someone of that age with IGF levels of 400 or
500. This is why these study findings seem very
unusual.
IGFBP-3 is one of the
blinding proteins that carries IGF. This seemingly
simple system is actually very complex. All the
binding proteins are hormones in their own right; they
do not just provide storage for the hormones. So the
highest quartile had a 2.4 times increased relative
rise of prostate cancer. When a patient is treated
with GHRT, IGF-1 levels increase and levels of IGFBP-3
also increase. Thus, GH stimulates the production of
both IGF and IGFBP-3. In the study by Chang et al the
men with more IGFBP-3 had a decreased risk of prostate
cancer.
IGFBP-3 has been called
the guardian of the genome. IGF-1 does have a
mitogenic effect: it does cause cellular replication
and renewal. However, the mitogenic effect of IGF-1 is
balanced by the apoptotic effect of IGFBP-3. IGFBP-3
triggers apoptosis in cancer cells. Thus IGFBP-3 plays
an important role in cancer control. However, too much
apoptosis would cause cellular aging. So it is
important that the body gets the balance just right.
A study of 765 men by
Scheafer et al found no association with IGF-1 and
prostate cancer. However, another study by Baffa et al
linked low IGF-1 levels with prostate cancer. It is
clear that we have conflicting evidence. However, if
the Chan study is the one and only reason to link GH
with increased risk of cancer, that reason is not
valid.
GROWTH HORMONE REPLACEMENT AND SIDE-EFFECTS
The most common side-effects of GHRT are edema,
arthralgia, and insulin resistance. Vance et al
concluded that edema and arthralgia are related to the
dose schedule. Patients that are affected by edema or
arthralgia are often being treated on a low-frequency,
high-dose schedule. They are also associated with
mg/kg does instead of a gradually increasing dose.
Both are reversible by simply decreasing the dose.
Another side-effect of
GHRT is paresthesia. If a patient complains of
paresthesia, or edema, or arthralgia, the best thing
to do is stop their treatment for a few days, decease
the dose, and maybe treat them symptomatically with
NSAIDs or mild diuretics. Potassium replacement can
also help to ameliorate these symptoms. In rare cases,
a patient cannot tolerate GH. If their arthralgia or
other adverse effect keeps recurring, GHRT is not for
them and should be discontinued.
GHRT can cause insulin
resistance. But this can be avoided if the patient is
managed correctly. It is vital that the patient eats
correctly. We have the Atkins' diet, the Zone diet,
and the Paleolithic diet. All three of these diets are
pointing towards the same thing: that we need protein,
good-quality fats, and that we have to choose our
carbohydrates carefully, that is, obtain them from
vegetables. So before a patient embarks on an
anti-aging program, it is vital that they eat
properly. Testosterone replacement therapy decreases
insulin resistance. And so a patient with borderline
insulin resistance who wants to be treated with GHRT
may benefit from being treated with testosterone
first. Diabetics need to be advised that their insulin
requirements could go up or down.
Nam et al evaluated the
effects of low-dose GH therapy combined with diet
restriction on changes in body composition and insulin
resistance in newly diagnosed obese type 2 diabetic
patients. The findings led them to conclude: "Low-dose
GH treatment combined with dietary restriction
resulted not only in a decrease of visceral fat but
also an increase of muscle mass with a consequent
improvement of the insulin resistance observed in
obese type 2 diabetic patients." Remember, obesity is
another inflammatory disease. Abdominal fat makes
IL-6, and IL-6 causes insulin to go up and store more
fat: thus creating one big cycle.
CONCLUSION
In conclusion, given the state of scientific medical
knowledge today, GH is safe. GHRT is associated with
less morbidity and mortality, less cardiovascular
disease, less inflammation, improvements in body
composition, improvements in exercise capacity, and a
better quality of life. In the words of Peter Sonksen:
"GH is essential for normal adult life, and without it
life expectancy is shortened, energy and vitality are
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.
REFERENCES
Adamopoulos S, Parissisc
JT, Georgiadis M, Karatzas D, Paraskevaidis J, Kroupis
C, Karavolias G, Koniavitou K, Kremastios DT. Growth
hormone administration reduces circulating
proinflammatory cytokines and soluble Fas/soluble Fas
ligand system in patients with chronic heart failure
secondary to idiopathic dilated cardiomyopathy. Am
Heart J. 2002; 144:359-364.
Aleman A, Verhaar HJ, De
Haan EH, De Vries WR, Samson MM, Drent ML, Van der
Veen EA, Koppeschaar HP. Insulin-like growth factor-I
and cognitive function in healthy older men. J Clin
Endocrinol Metab. 1999;84:471-475.
Baffa R, Reiss K, El-Gabry
EA, Sedor J, Moy ML, Shupp-Byrne D, Strup SE, Hauck
WW, Baserga R, Gomelia LG. Low serum insulin-like
growth factor 1 (IGF-1): a significant association
with prostate cancer. Tech Urol. 2000; 6:236-239.
Blackman MR. Age-related
alterations in sleep quality and neuroendocrine
function: interrelationships and implications. JAMA
2000; 284: 879-881.
Borson-Chazot F,
Serusclat A, Kalfallah Y, Ducottet X, Sassolas G,
Bernard S, Labrousse F, Pastene J, Sassoas A, Roux Y,
Berthezene F. Decrease in carotid intima-media
thickness after one year growth hormone (GH) treatment
in adults with GH deficiency. J Clin Endocrinol Metab.
1999;84:1329-1333.
Burgess W, Liu Q, Zhou
J, Tang Q, Ozzawa A, VanHoy R, Arkins S, Dantzer R,
Kelley KW. The immune-endocrine loop during aging;
role of growth hormone and insulin-like growth
factor-1. Neuroimmunomodulation. 1999;6:56-68.
Cappola
AR, Bandeen-Roche K, Wand GS, Volpato S, Fried LP.
Association of IGF-1 levels with muscle strength and
mobility in older women. J Clin Endocrinol Metab.
2001;86:4139-4146.
Cappola AR, Xue QL,
Ferrucci L, Guralnik JM, Volpato S, Fried LP.
Insulin-like growth factor-1 and interleukin-6
contribute synergistically to disability and mortality
in older women. J Clin Endocrinol Metab.
2003;88:2019-2025.
Chan JM, Stampfer MJ,
Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens
CH, Pollak M. Plasma insulin-like growth factor-1 and
prostate cancer risk: a prospective study. Science
1998;279:563-566.
Christiansen J. Effects
of GH upon body composition. Growth Hormone in Adults,
1196. Cambridge University Press.
Clark R.
The somatogenic hormones and insulin-like growth
factor-1: stimulators of lymphopoiesis and immune
function. Endocr Rev. 1997;18:157-179.
Gibney J, Wallace JD,
Spinks T, Schnorr L, Ranicar A, Cuneo RC, Lockhart S,
Burnand KG, Salomon F, Sonksen PH, Russell-Jones D.
The effects of 10 years of recombinant human growth
hormone (GH) in adult GH-deficient patients. J Clin
Endocrinol Metab. 1999;84:2596-2602.
Gillberg P, Mallmin H,
Petren-Mallmin M, Ljunghall S, Nilsson AG. Two years
of treatment with recombinant human growth hormone
increases bone mineral density in men with idiopathic
osteoporosis. J Clin Endocrinol Metab.
2002;87:4900-4906.
Gilchrist FJ, Murray RD,
Shalet SM. The effect of long-term untreated growth
hormone deficiency (GHD) and 9 years of GH replacement
on the quality of life (QoL) of GH- deficient adults.
Clin Endocrinol (Oxf). 2002;57:363-370.
Hedstrom M. Hip fracture
patients, a group of frail elderly people with low
bone mineral density, muscle mass and IGF-1 levels.
Acta Physiol Scand. 1999;167:347-350.
Johannsson G, Marin P,
Lonn L, Ottoson M, Stenlof K, Bjorntorp P, Sjostrom L,
Bengtsson BA. Growth hormone treatment of abdominally
obese men reduces abdominal fat mass, improves glucose
and lipoprotein metabolism, and reduces diastolic
blood pressure. J Clin Endocrinol Metab.
2001;86:3604-3610.
Molitch ME. Diagnosis of
GH deficiency in adults-how good do the criteria need
to be? J Clin Endocrinol Metab. 2002;87:473-476.
Munzer T, Harma SM, Hees
P, Shapiro E, Christmas C, Bellantoni MF, Stevens TE,
O'Connor KG, Pabst KM, St. Clair C, Sorkin JD,
Blackman MR. Effects of GH and/or sex steroid
administration on abdominal subcutaneous and visceral
fat in healthy aged women and men. J Clin Endocrinol
Metab. 201;86:3604-3610.
Nam SY,
Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB.
Low-dose growth hormone treatment combined with diet
restriction decreases insulin resistance by reducing
visceral fat and increasing muscle mass in obese type
2 diabetic patients. Int J Obes Relat Metab Disord.
2001;25:1101-1107.
Nyberg F. Growth hormone
in the brain: characteristics of specific brain
targets for the hormone and their functional
significance. Front Neuroendocrinol. 2000;21:330-348.
Pfeifer M, Verhovec R,
Zizek B, Prezelj J, Poredos P, Clayton RN. Growth
hormone (GH) treatment reverses early atherosclerotic
changes in GH-deficient adults. J Clin Endocrinol
Metab. 1999;84:453-457.
Ren J, Samson WK, Sowers
JR. Insulin-like growth factor 1 as a cardiac hormone:
physiological and pathophysiological implications in
heart disease. J Mol Cell Cardiol. 1999;31:2049-2061.
Rothenberg R. Quality of
Life Improves with GH Therapy. Anti-Aging Medical News
2002; Summer-Fall: 34.
Rudman D, Feller AG,
Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF,
Schlenker RA, Cohn L, Rudman IW, Mattson DE. Effects
of human growth hormone in men over 60 years old. N
Engl J Med. 1990;323:1-6.
Schaeffer A. Science
1998;281:1285.
Sesmilo G, Biller BM,
Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A.
Effects of growth hormone (GH) administration on
homocyst(e)ine levels in men with GH deficiency: a
randomized controlled trial. J Clin Endocrinol Metab.
2001; 86:1518-1524.
Shalet SM, Brennan BM,
Reddingius RE. Growth hormone therapy and malignancy.
Horm Res. 1997;48 Suppl :29-32.
Slonim AE, Bulone L,
Damore MB, Goldberg T, Wingertzahn MA, McKinley MJ. A
preliminary study of growth hormone therapy for
Crohn's disease. N Engl J Med. 2000;342: 1633- 1637.
Sonksen PH. Growth
hormone replacement in adults with GH deficiency-the
first 10 years. Growth Horm IGF Res. 1998;8:275-276.
Swerdlow AJ, Higgins CD,
Adlard P, Preece MA. Risk of cancer in patients
treated with human pituitary growth hormone in the UK,
1959-85: a cohort study. Lancet. 2002;360:273-277.
Swerdlow AJ, Reddingius
RE, Higgins CD, Spoudeas HA, Phipps K, Qiao Z, Ryder
WD, Brada M, Hayward RD, Brook CG, Hindmarsh PC,
Shalet SM. Growth hormone treatment of children with
brain tumors and risk of tumor recurrence. J Clin
Endocrinol Metab. 2000;85:4444-4449.
Tacke J, Bolder U,
Hermann A, Berger G, Jauch KW. Long-term risk of
gastrointestinal tumor recurrence after postoperative
treatment with recombinant human growth hormone. J
Parenter Enteral Nutr. 2000;24:140-144.
Takala J, Ruokonen E,
Webster NR, Nielsen MS, Zandstra DF, Vundelineckx G,
Hinds CJ. Increased mortality associated with growth
hormone treatment in critically ill adults. N Engl J
Med. 1999;341:785-792.
Van der Lely AJ,
Lamberts SW, Jauh KW, Swierstra BA, Hertlein H,
Danielle De Vries D, Birkett MA, Bates PC, Blum WF,
Attanasio AF. Use of human GH in elderly patients with
accidental hip fracture. Eur J Endocrinal.
2000;143:585-592.
Vance ML, Muras N.
Growth hormone therapy in adults and children. N Engl
J Med. 1999;341:1206-1216.
Verhelst J, Abs R.
Long-term growth hormone replacement therapy in
hypopituitary adults. Drugs 2002;62:2399-2412.
Weltman A, Weltman JY,
Veldhuis JD, Hartman ML. Body composition, physical
exercise, growth hormone and obesity. Eat Weight
Disord. 2001;6:28-37.
ABOUT
THE AUTHOR
As a pioneer in the field of Anti-Aging Medicine, Ron
Rothenberg, M.D, was one of the first physicians to be
recognized for his expertise to become fully board
certified in the specialty by the American Board of
Anti-Aging Medicine (ABAAM). Dr. Rothenberg founded
the California HealthSpan Institute in Encinitas,
California in 1997 with a commitment to transforming
our understanding of and finding treatment for aging
as a disease. Dr. Rothenberg is dedicated to the
belief that the process of aging can be slowed,
stopped, or even reversed through existing medical and
scientific interventions. Challenging traditional
medicine's approach to treating the symptoms of aging,
California HealthSpan's mission is to create a
paradigm shift in the way we view medicine: treat the
cause.
Dr. Rothenberg received
his M.D from Columbia University, College of
Physicians and Surgeons in 1970. He performed his
residency at Los Angeles County-USC Medical Center and
is also board certified in Emergency Medicine. He
received academic appointment to the UCSD School of
Medicine Clinical Faculty in 1977 and was promoted to
full Clinical Professor of Preventive and Family
Medicine in 1989. In addition to his work in the field
of Anti-Aging Medicine, Dr. Rothenberg is an Attending
Physician and Director of Medical Education,
Department of Emergency Medicine, Scripps Memorial
Hospital in Encinitas, California.
Dr. Rothenberg travels
extensively to lecture on a variety of topics, which
include Anti-Aging, Medicine and Wilderness Medicine.
He has published in the fields of Anti-Aging Medicine
and Emergency Medicine, and is the author of Forever
Ageless. He has been featured in the University of
California MD TV series in the shows on Anti-Aging
Medicine and in the NBC network news discussing
anti-aging medicine.
Dr. Rothenberg is the
Director of Medical Education of the American Board of
Mesotherapy and the Bissoon Institute of Mesotherapy
and has an active mesotherapy practice. Continuing his
quest to offer his patients the latest and most
effective medicine, he is amongst the first 15
physicians in the United States to be board certified
in this specialty.
