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SOMATOPAUSE, GROWTH HORMONE, IGF- I |
Frequently Asked Questions (FAQs)
This information is under copyright by Harvey S. Bartnof,
M.D. and California Longevity and Vitality Medical Institute®.
It may be copied only for individual, personal use and is not
for distribution or publication of any type without the explicit
written permission of Dr. Bartnof. All information presented is
referenced in the Reference section below.
What Is Somatopause?
What Are the Features of Somatopause?
What Is Classical Growth Hormone Deficiency?
How Is Somatopause Different From Classical
Hormone Deficiency?
What Are The Body Changes With Traditional
Growth Hormone Deficiency?
What Are The Mental Changes With Traditional
Growth Hormone Deficiency?
What Are The Blood Changes With Traditional
Growth Hormone Deficiency?
What Are The Side Effects Of Growth Hormone
Treatments?
Who Is Not a Candidate for Growth Hormone?
If I Am Diabetic, Is It Okay To Take Growth
Hormone?
11 Notable Quotations About Somatopause And
Growth Hormone
References
What Is Somatopause?
Somatopause refers to a decline in the blood levels of
growth hormone (GH, somatotropin) and another hormone
that GH converts into, called IGF-I or somatomedin. As of
May 2004, somatopause is now referenced in 40 citations in
PubMed, the online library of the National Institutes of Health,
as well as in a few standard Endocrinology (study of glands)
medical textbooks. Growth hormone secretion starts to decrease
when someone is in their mid 20s and decreases
approximately 14% per decade. (Note that before modern
civilization, the average lifespan was less than 30 years!)
Similar to growth hormone, IGF-I levels also begin to decline
when someone is in his/her 20s. In fact, IGF-I blood levels are
20-80% lower in healthy elderly persons than in young adults.
There is a significant amount of research indicating that the
features of somatopause in the elderly (and in some of
middle-age) are very similar to those of Classical Growth
Hormone Deficiency (see FAQs below for symptoms and body
changes). And there are several smaller studies indicating that
when elderly people with somatopause are treated with growth
hormone, many of those abnormal features improve and some even
resolve. (This is quite similar to what happens when those
with Classical Growth Hormone Deficiency are treated with growth
hormone.) However, long-term studies of treating Somatopause are
lacking. Medical researchers have also used other terms to
describe somatopause, including geriatric hyposomatotropism (low
growth hormone) and hyposomatomedinemia (low IGF-I in blood).
What Are the Features
of Somatopause?
The features are quite similar to those seen in Classical Growth
Hormone Deficiency. All of the features that are listed here are
referenced in the Reference section below. Note that some of
these features may have multiple causes or co-factors and may
not be solely due to a decline in Growth Hormone. They include:
increased fat mass, particularly around the waistline and
abdomen (“visceral,”); decreased muscle mass and
strength; decreased bone density with possible osteopenia
and osteoporosis and increased risk of fracture; abnormal
blood lipids (high LDL or “bad” cholesterol, decreased HDL
or “good” cholesterol); impaired glucose (sugar)
tolerance and/or insulin resistance (“pre-diabetes”);
increased CRP (C-reactive protein) and possibly IL-6
(interleukin-6, both are inflammatory markers; elevated CRP
increases the risk for heart attack, stroke, Alzheimer’s and
cancers); possible increased homocysteine (increases risk
of heart attack, stroke and osteoporosis or low bone density);
decreased total body water (with possibility for
shrinkage of many organs); possible increased risk of angina
(heart pain due to inadequate blood supply) and heart attack;
possible increase in atherosclerosis, including increased
“intima media” thickness in carotid (neck) arteries and
elsewhere. Low bone density and decreased total body water are
co-factors for a loss in height that commonly occurs in
the elderly.
Newer research has specifically linked low growth hormone/ IGF-I
with heart attack and heart disease risk (see references
below) and osteoporosis (low bone density). A few studies
have shown benefits in treating osteoporosis with growth
hormone (see references below).
Possible mental or psychic changes are not as well documented in
somatopause, but clearly exist in Classical Growth Hormone
Deficiency (see below) and quite possibly exist in Somatopause.
This would not be surprising, since there are numerous
receptors for Growth Hormone throughout the brain. In fact,
newer research suggests that somatopause itself, appears to be a
cause or co-factor for declining cognition (thinking,
understanding) and even Alzheimer’s Disease. Other
research has linked low growth hormone with abnormal sleep
patterns commonly seen in the elderly (see references
below).
Also, somatopause may be a cause or co-factor for a declining
immune system that frequently occurs in the elderly. IGF-I
is needed for lymphocyte maturation and function, while growth
hormone may lead to a restoration of T- and B-lymphocytes.
What Is Classical
Growth Hormone Deficiency?
This hormonal deficiency was first observed by physicians in
children who were short for their age (“dwarfism” or
“vertically-challenged”). They were lacking or low in growth
hormone. This could be congenital (at birth) or manifest later
in childhood. Subsequently, an adult form was recognized, with
features as described below. Some of these people (children or
adults) had a tumor (cancer) in their pituitary gland (base of
brain) that crowded out the cells that would normally secrete
growth hormone. The other side of that story means that in young
adulthood, almost all of the rest of people (without Growth
Hormone Deficiency) had some growth hormone that in some way was
contributing to their being normal and remaining healthy. It
is in this majority that growth hormone is functioning more as a
“maintenance” hormone, rather than a “growth” hormone. This
means, in part, that growth hormone helps to maintain the size
of each organ after its peak size was reached in puberty due to
the growth effects of GH.
Classical Growth Hormone (GH) Deficiency is diagnosed by
a patient’s history (symptoms), physical examination and
laboratory tests. The gold standard in establishing the
diagnosis is a GH stimulation test. After an intravenous (“IV”)
line has been established, an infusion of insulin or arginine
plus GHRH (growth hormone releasing hormone) is given (other IV
stimulators are sometimes used). This provides a signal to the
pituitary gland to secrete growth hormone. After a short period,
a blood sample is taken to measure the level of GH. If it is
below a designated level, then a diagnosis of Growth Hormone
Deficiency may be made.
How Is Somatopause
Different From Classical Hormone Deficiency?
Despite a body of increasing evidence (see Reference list), many
physicians remain unconvinced that Somatopause exists. They
believe that all aspects of aging are essentially inevitable—and
that each chronic condition should be treated with patented
drugs, without considering that underlying hormone deficiencies
may be at least a co-factor. Yet there is increasing evidence
that at least part of several aspects of aging is due to a
decline in one or more hormones. This includes somatopause,
andropause
(decline in male hormones),
female
menopause,
adrenopause , and others. In fact, it has been documented
that many physicians remain unconvinced that a diagnosis of
Classical Growth Hormone Deficiency in adults should be pursued
at all.
A main difference between somatopause and GH Deficiency is the
recognition that somatopause in middle age or elderly may be
a more moderate form of Classical GH deficiency, yet with
features that are quite similar or perhaps milder.
Additional research would help to clarify specific differences.
However, it has been shown that as cells (and therefore organs
and humans) age, their overall efficiency decreases. This
includes decreasing efficiency of mitochondria (energy producers
in cells), accumulated glycation (abnormal attaching of glucose)
of proteins and other cellular constituents, mitochondrial and
somatic (in nucleus or center of cell) DNA mutations,
accumulation of lipofuscin (by-products) pigments in cells and
cumulated oxidative damage. These changes might be associated
with a decrease in the amount of or the effects from many
chemical messengers in the body, including certain hormones.
This, in turn, may be one cause of declines that occur in many
organ systems in the elderly.
Untreated Classical Growth Hormone Deficiency is associated with
a much shorter lifespan, often due to accelerated
atherosclerosis (artery disease) and premature heart attack.
There is now a study indicating that somatopause (low IGF-I)
itself also is associated with ischemic (low blood flow) heart
disease in men and women, with an incrementally higher risk of
heart disease associated with incrementally lower IGF-I levels
(see Laughlin
reference
below). Another study found
a significant association between low IGF-I levels and
decreased lifespan in men (Ruiz-Torres
reference below).
What Are The Body
Changes With Traditional Growth Hormone Deficiency?
The changes include: increased body fat on the trunk,
particularly around the waistline and inside the abdomen
(“visceral” fat); decreased muscle mass and strength;
variable decreased cardiac (heart) muscle mass
associated with impaired functioning and decreased exercise
capacity; low bone mineral density (osteopenia
and possibly osteoporosis), with resulting increased risk of
bone fracture; increased artery (“intima media”)
thickness (a manifestation of atherosclerosis)
particularly in the carotid (neck) arteries; decreased
total body water (both in and between cells) associated
with organs that are smaller (and in part, along with
osteoporosis, height loss); decreased collagen in
the skin and other tissues, that is associated with
less elasticity and wrinkling as well as skin that is
thin and dry (also due to water loss); and in those with
deficiency from childhood who were never treated, short height
and increased skin wrinkling for age.
What Are The Mental
Changes With Traditional Growth Hormone Deficiency?
A decrease in each of the following has been reported: mood,
quality-of-life, energy, vitality, and well being; with an
increase in anxiety and depression--social isolation may also
occur. All of these parameters improve or normalize after
treatment with Growth Hormone (Gilchrist
reference below). New research links low IGF-I with risk of
Alzheimer’s disease (see reference below).
What Are The Blood
Changes With Traditional Growth Hormone Deficiency?
The changes include: abnormal blood lipids (fats), i.e.
increased LDL-cholesterol (“bad” type), decreased
HDL-cholesterol (“good” type) and increased “apo B;”
glucose intolerance and/or insulin-resistance (both
are “pre-diabetes” states); increased fibrinogen and
PAI-1 (plasminogen activator inhibitor type 1) both of which
increase the risk for heart attack, stroke and possibly
Alzheimer’s disease; and increased inflammation markers CRP
and IL-6 (interleukin-6). Increased CRP is an independent
risk factor for heart attack, stroke, Alzheimer’s disease and
certain cancers.
What Are The Side
Effects Of Growth Hormone Treatments?
Since growth hormone helps to maintain water in the body (in
cells, in-between cells, in most organs), the most common side
effect is water retention. Side effects due to retained water
can be minimized with proper dosage, especially when first
starting treatment. Retained water may manifest as swelling
in the fingers, hands, feet or ankles, joint aches, muscle
aches, or tingling in some fingers (“carpel tunnel syndrome” due
to swelling where the nerve passes through wrist bones). Also,
specific dose modifications or treatments (prescriptive and
non-prescriptive) may minimize or completely eliminate these
symptoms. In addition, symptoms tend to decrease with time.
Other reported side effects include “glucose intolerance”
or insulin resistance (types of pre-diabetes), but with
appropriate lifestyle modification, usually this risk can be
avoided or minimized. Some patients experience an improvement in
insulin resistance after a month or so of treatment. Some
studies have shown an increase in blood pressure, but many
people will experience no change or even a decrease in blood
pressure, due to a decrease in fat in the trunk and abdomen,
with an associated decrease in weight and decrease in
“angiotensinogen” (increases risk of high blood pressure). Some
patients may report symptoms of gynecomastia, or
enlargement of the breasts. This is most likely associated with
changes in levels of certain sex hormones that might occur with
growth hormone therapy, and this is treatable and/or
preventable. Uncommon side effects include “benign
intracranial hypertension” (high brain pressure with headaches),
pancreatitis (inflammation of organ in abdomen), and thyroid
hormone changes.
The potential for all of these side effects means ongoing and
careful monitoring of symptoms, physical examination and
blood tests. As with any treatment, patients are monitored for
side effects and if the risks or side effects begin to outweigh
the potential benefits, then a decision is made to discontinue
therapy.
Who Is Not a
Candidate for Growth Hormone?
The following people would not be a candidate for Growth Hormone
therapy: those with benign intracranial hypertension (high
pressure in the brain, uncommon); proliferative or
preproliferative diabetic retinopathy (abnormal blood vessel
growth in the back of the eye); acute, critical illness in the
intensive care unit; pulmonary fibrosis; HIV/AIDS with an active
malignancy (cancer); and any active malignancy (cancer).
However, that latter category is debated among specialists. The
Growth Hormone Research Society (see reference below) has stated
that since there is no good evidence supporting that
contraindication, the FDA package label should be modified (see
Notable Quotations below, #8). The
American Association of Clinical Endocrinologists states that
growth hormone may be used in someone who has had no evidence of
his/her cancer for at least 5 years. Recall that growth hormone
actually stimulates parts of the immune system, including that
which is involved in cancer surveillance.
If I Am Diabetic, Is
It Okay To Take Growth Hormone?
There is some very interesting research showing that growth
hormone may show benefits for those with type II diabetes (Nam
reference below . When compared to a placebo (inactive drug
group), growth hormone actually decreased insulin resistance,
decreased body fat (including abdominal fat), increased lean
(muscle, bone) mass, and increased “glucose disposal.” However,
larger doses of growth hormone were used in that study. Note
that when diabetics use growth hormone, their dose of diabetes
medication may decrease or sometimes (initially) increase.
Therefore, there may an initial worsening of diabetic control.
11 Notable
Quotations About Somatopause And Growth Hormone
1. “Somatopause occurs in early adulthood, between age
25-35 years, an age range that corresponds to the human life
expectancy before the development of modern civilization.”
(Dr. Eve Van Cauter of the
Department of Medicine at University of Chicago in Journal of
the American Medical Association, August 2000,
reference below).
2. “The term ‘somatopause’ has been used by some
investigators to suggest that normal aging is associated with a
gradual decline in secretion of GH accompanied by a decrease in
bone mass and lean body mass as well as an increase in adipose
[fat] mass.”
(Growth Hormone
Guidelines, published by the American Association of Clinical
Endocrinologists, see reference below)
3. “The fall in growth hormone secretion seen with ageing
coincides with changes in body composition and lipid [fat]
metabolism that are similar to those seen in adults with growth
hormone deficiency.” (Dr.
R. Savine, Department of Medicine, St Thomas' Hospital, London,
UK in Hormone Research, 2000, reference below)
4. “The effects of six months of human growth hormone on
lean body mass and adipose-tissue mass (in elderly men) were
equivalent in magnitudes to the changes incurred during
10-20 years of aging.”
(Daniel Rudman, MD, New England
Journal of Medicine, July 1990, reference
below)
5. “The Growth Hormone Research Society…concluded that Growth
Hormone therapy is not associated with the promotion
of any pituitary [in the brain] tumor recurrence or the
development of any other neoplasm [cancer].”
(Consensus Guidelines reference from
The Growth Hormone Research Society below, 1998
reference below)
6. “…no evidence that growth hormone-replacement therapy
[adversely] affects the risk of cancer or cardiovascular
disease.” (Mary Lee Vance,
MD, Department of Internal Medicine, University of Virginia
Medical Center, New England Journal of Medicine, October 1999,
reference below)
7. “Although there has been some concern abut an
increased risk of cancer, reviews of existing,
well-maintained databases of treated patients have shown this
theoretical risk to be nonexistent.”(Dr.
M.E. Molitch, The Feinberg Medical School, Northwestern
University, Chicago,
Journal of Clinical Endocrinology and Metabolism, February 2002,
reference below)
8. “The current labeling for Growth Hormone
(GH) states that active malignancy is a contraindication [reason
not to use] for GH treatment. There are, however, no data to
support this labeling. Current knowledge does not warrant
additional warning about cancer risk in the product label.”
(Critical Evaluation Of The Safety Of Recombinant Human Growth
Hormone Administration: Statement From the Growth Hormone
Research Society. Journal of Clinical Endocrinology and
Metabolism. May 2001, reference below)
9. “All of the evidence shows that growth hormone is
one of the safest drugs we have. Thousands of patients have
been followed for the past 16 years,”
(Pinchas Cohen, MD,
Director of Pediatric Endocrinology at University of California
at Los Angeles School of Medicine, Newsweek, September 23, 2003)
10. “Growth hormone is not a ‘fountain of youth;’ if we were to
stay perfect, why alter a perfect system?” (Ronald Rothenberg,
MD, Clinical Professor of Family and Preventive Medicine at
University of California at San Diego School of Medicine)
11. “Primum non nocere” (Latin for first do no harm, a quote
medical students learn in their first year of medical school)
References
References-Somatopause, Aging,
General
References-Longevity and Growth
Hormone/ IGF-I
References-Growth Hormone Treatment
Studies in Elderly
References-Heart and Arteries and
Growth Hormone/ IGF-I
References-Muscle, Bone Density,
Osteoporosis, Fractures
References-Mental, Cognitive
[Thinking] Decline, Alzheimer’s Disease
References-Reports About Cancer Risks From
Growth Hormone/ IGF-I
[Cancer])
References-Sleep and Growth Hormone
References-Immune System and Growth Hormone/
IGF-I
References-Heart Failure, Cardiomyopathy
[enlarged diseased heart] and Growth Hormone
References-Diabetes, Obesity, Metabolic
Syndrome and Growth Hormone
References-Tissue Healing and Growth Hormone
References-Erectile Dysfunction and Growth
Hormone
References-Classical Growth Hormone
Deficiency
References-Acromegaly (Abnormally High Growth
Hormone Due to a Tumor [Cancer])
Professional Societal Practice Guidelines
References-Somatopause, Aging, General
Ron Rothenberg MD and Kathleen Becker, MA, RN. Forever
Ageless. (2001, California Healthspan Institute, editor,
Encinitas, CA).
Growth hormone - hormone replacement for
the somatopause?
Savine R, Sonksen P. Hormone Research. 2000; 53 Suppl
3:37-41.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10971102
“Twenty-four-hour growth
hormone (GH) secretion reaches a peak at around puberty and by
the age of 21 has begun to decrease. Thereafter the fall in GH
secretion is progressive such that by the age of 60 most adults
have total 24-hour secretion rates indistinguishable from those
of hypopituitary [low brain hormone signal] patients with
organic lesions [severe abnormality or pathology] in the
pituitary gland.”
Is the somatopause
an indication for growth hormone replacement?
Savine R, Sonksen PH. Journal Endocrinol Invest.
1999; 22(5 Suppl): 142-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10442584
“Life without GH is poor
both in quantity and quality”
Somatopause
Lamberts SWJ. In Endocrinology of Aging (chapter 25),
Williams Textbook of Endocrinology 10th Edition, Larsen et
al, editors (2003, Saunders-Elsevier, publishers), pp.
1297-1298.
Can growth hormone prevent
aging?
Vance ML. New England Journal of Medicine. 2003 Feb
27; 348(9): 779-80 (no abstract on PubMed).
Is there an antiaging
medicine?
Butler RN, Fossel M, Harman SM and others. J Gerontol A
Biol Sci Med Sci. 2002 Sep; 57(9): B333-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12196485
Growth hormone therapy in adults and
children.
Vance ML, Mauras N. New England Journal of Medicine.
1999 Oct 14; 341 (16): 1206-16 (review, no abstract on PubMed).
“…no evidence that
growth hormone-replacement therapy affects the risk of cancer
or cardiovascular disease.”
References-Longevity and Growth Hormone/ IGF-I
The prospective association of serum
insulin-like growth factor I (IGF-I)
and IGF-binding protein-1 levels with all cause and
cardiovascular disease
mortality in older adults: the Rancho Bernardo Study.
Laughlin GA, Barrett-Connor E and others. Journal of
Clinical Endocrinology and Metabolism. 2004 Jan; 89(1):
114-20.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14715837
Low baseline levels of
IGF-I increase the risk of fatal ischemic [low blood] heart
disease among elderly men and women independent of prevalent
heart disease and cardiovascular risk factors. The relative risk
of heart disease mortality was a significant 38% higher for
every 40 ng/ml decrease in IGF-I. Study involved 633 men and 552
nonestrogen-using postmenopausal women, aged 51-98 yr (mean, 74
yr) in 1988-1992, who were followed through July 2001 (96%
follow-up), representing 9-13 years of follow-up,
Ageing and
longevity are
related to growth hormone/ insulin-like growth factor-1 (GH/
IGF-I) secretion.
Ruiz-Torres A, Soares de Melo Kirzner M. Gerontology.
2002 Nov-Dec; 48(6): 401-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12393957
“Old males (older than 70
years) with IGF-I levels similar to young ones (younger than 39
years) do not show the age-dependent decrease in serum
testosterone and lean [muscle, bone] body mass, nor the increase
in fat body mass; old
men having low IGF-I blood levels die earlier.”
References-Growth
Hormone Treatment Studies in Elderly
Growth hormone and sex steroid
administration in healthy aged women and men: a randomized
controlled trial.
Blackman MR, Sorkin JD and others. Journal of the American
Medical Association. 2002 Nov 13; 288(18): 2282-92.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12425705
26-week study in healthy,
ambulatory, US women (n = 57) and men (n = 74) aged 65 to 88
years given growth hormone with or without sex steroids. Results
showed increased lean
body mass and
decreased fat mass, with maximal changes in both sexes
receiving both GH and sex hormone(s). Sex steroid + GH increased
muscle strength
marginally and exercise capacity in men, but not women
had. Side effects related to growth hormone included (note older
dosing schedule) swelling, carpal tunnel symptoms (tingling
fingers) and joint aches. Diabetes or glucose intolerance
occurred in 18 GH-treated men (though baseline overweight, no
diet change, no exercise).
Growth hormone and sex steroid effects on bone metabolism and
bone mineral density in healthy aged women and men.
Christmas C, O'Connor KG, Harman SM and others. J
Gerontol A Biol Sci Med Sci. 2002 Jan; 57(1): M12-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11773207
Same 26-week patient
study as JAMA Nov 13, 2003 above) Other results: short-term
administration of female hormone replacement therapy exerts
beneficial effects on bone metabolism and bone mineral density
in postmenopausal women, which are not significantly altered by
the co-administration of growth hormone. In andropausal men,
testosterone administration to achieve physiologic levels did
not result in significant effects on bone metabolism or bone
mineral density, whereas growth hormone plus testosterone
increased one marker of bone formation and decreased one marker
of bone resorption.
Growth hormone replacement in healthy older men improves body
composition but not functional ability.
Papadakis MA, Grady D and others. Annals of Internal Medicine.
1996 Apr 15; 124(8): 708-16.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8633830
52 healthy men mean age 75
years (70-85) with well-preserved functional ability but low
baseline IGF-I. Growth hormone or placebo given for 6 months.
Results showed increased
lean tissue mass 4.3% and decreased fat mass 13%, yet
functional ability did not improve. Side effects occurred
frequently. The mean
Trails B score in the growth hormone group
improved significantly
by 8.5 seconds.
Effects of human growth hormone in men
over 60 years old.
Rudman D, Feller AG and others. New England Journal of
Medicine. 1990 Jul 5; 323(1): 1-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2355952
21 men ages 61-81 years
given growth hormone for 6 months. Results showed IGF-I level
rose into the youthful range, 8.8 percent increase in lean body
mass, a 14.4 percent decrease in adipose (fat) mass, and a 1.6
percent increase in average lumbar vertebral bone density (all
significant changes).
Skin thickness increased 7.1 percent (P = 0.07). Side
effects included small increases in fasting glucose and blood
pressure. Authors concluded that
diminished secretion of
growth hormone is responsible in part for the decrease of lean
body mass, the expansion of adipose-tissue mass, and the
thinning of the skin that occur in old age.
References-Heart
and Arteries and Growth Hormone/ IGF-I
Insulin-like growth factor I (IGF-I)
as a cardiac [heart]
hormone: physiological and pathophysiological
implications in heart disease.
Ren J, Samson WK, Sowers JR. J Mol Cell Cardiol. 1999
Nov; 31(11): 2049-61.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10591031
IGF-I plays a specific
role in cardiovascular function.
IGF-I promotes cardiac
growth, improves cardiac contractility, cardiac output, stroke
volume, and ejection fraction (measurements of heart
function). In humans, IGF-I improves cardiac function after
myocardial infarction by stimulating contractility and promoting
tissue remodeling. IGF-I facilitates glucose metabolism, lowers
insulin levels, increases insulin sensitivity, and improves the
lipid profile. Both clinically observed and experimentally
induced impairments of cardiac function also found to be
associated with abnormal IGF-I levels. IGF-I and its binding
proteins have been considered as markers for the presence of
certain cardiac abnormalities, indicating that IGF-I may be a
risk factor for certain cardiac disorders.
Reduced levels
of insulin-like growth factor-1 (IGF-I)
in patients with angina pectoris [heart
pain associated with inadequate blood supply], positive exercise
stress test, and angiographically normal epicardial coronary
arteries.
Conti E, Andreotti F and others. American Journal of
Cardiology. 2002 Apr 15; 89(8): 973-5.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11950439
Markedly reduced
insulin-like growth factor-1 (IGF-I)
in the acute phase of myocardial infarction [heart
attack].
Conti E, Andreotti F and others. J Am Coll Cardiol.
2001 Jul; 38(1): 26-32.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11451284
In the early phase of a
heart attack, serum IGF-I levels are markedly reduced and may
contribute to adverse outcomes. Reduced IGF-I precedes the rise
of myocardial necrosis [heart cell death] markers suggests a
possible pathogenetic [disease-causing] role.
Growth hormone improves cardiac function in rats with
experimental myocardial infarction [heart attack].
Isgaard J, Kujacic V and others. Eur J Clin Invest.
1997 Jun; 27(6): 517-25.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9229233
In rats with heart attack,
13% increase in ejection
fraction and a 50% increase in cardiac index [heart function
measurements] when treated with growth hormone compared
with control rats. Moreover, GH caused a significant decrease in
end-systolic volume. GH in a physiological dose improves
systolic function in an experimental model of heart failure
without signs of hypertrophy [enlargement], suggesting a
potential role as a therapeutic agent in the treatment of heart
failure and merits further investigation.
Effects of early treatment with growth hormone on infarct
size, survival, and cardiac gene expression after acute
myocardial infarction [heart
attack, rats].
Jin H, Yang R and others. Growth Horm IGF Res. 2002 Aug;
12(4): 208-15
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12175653
In rats with heart attack, growth
hormone decreased infarct [dead heart cell] size by a
significant 18% and increased survival by 36% at 52 weeks.
Endogenous hormones and
carotid atherosclerosis
in elderly men.
van den Beld AW, Bots ML and others. Am J Epidemiol. 2003
Jan 1; 157(1): 25-31.
Endogenous [within the
body] testosterone,
estrone, and free IGF-I levels may play a
protective role
in the development of
atherosclerosis in aging men; testosterone, estrone, and
free IGF-I were inversely related to intima-media [artery wall]
thickness. The strength of these relations was as powerful in
subjects with as in those without prevalent cardiovascular
disease.
References-Muscle, Bone Density, Osteoporosis, Fractures
Association of IGF-I
levels with muscle
strength and
mobility in older
women.
Cappola AR, Bandeen-Roche K and others. Journal of Clinical
Endocrinology and Metabolism. 2001 Sep; 86(9): 4139-46.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11549640
In a study population of
617 women age 70-79 years including frail and healthy older
women, low IGF-I
levels were associated with
poor knee
extensor muscle
strength, slow walking speed, and self-reported
difficulty with mobility
tasks. These findings suggest a role for IGF-I in
disability as well as a potential target population for
interventions to raise IGF-I levels.”
Growth hormone
administration and
exercise effects on
muscle fiber type
and diameter in moderately frail older people.
Hennessey JV, Chromiak JA and others. J Am Geriatr
Soc. 2001 Jul; 49(7): 852-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11527474
Significant increase in
the proportion of muscle type 2 fibers between baseline
and six months in the combined growth hormone-treated subjects
versus those not receiving it. Muscle strength increased
significantly in both the growth hormone plus exercise (+55.6%)
as well as the exercise alone (+47.8%) groups.
Hip fracture
patients, a group of
frail elderly people with low bone mineral density,
muscle mass and
IGF-I levels.
Hedstrom M. Acta Physiol Scand. 1999 Dec; 167(4):
347-50.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10632638
Lower IGF-I level and
lower bone and lean body mass in hip fracture patients
than in an age-matched group of patients. This sign of
catabolism [tissue break-down] seems to continue postoperatively
[after hip replacement], with a significant decrease of both BMD
and lean body mass possibly indicating GH/ IGF-I therapy
together with adequate nutrition to preserve bone and muscle
losses in elderly patients with hip fractures.
Use of human GH
in elderly patients with accidental
hip fracture.
Van der Lely AJ, Lamberts SW and others. Eur J Endocrinol.
2000 Nov; 143(5): 585-92.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11078981
111 patients older than 60
years with accidental hip fracture (mean age 78.5 years) were
randomized to receive either growth hormone or placebo for a
period of 6 weeks, starting within 24 h after the hip fracture
accident. Thereafter patients were followed up for an additional
period of 18 weeks. Results: significantly
higher proportion of
treated patients returning to the pre-fracture living situation
for subjects older than 75 years (93.8 vs 75.0%). Treatment
increased IGF-I values to levels in the range of those of normal
subjects of 50-60 years of age.
Effect of recombinant human growth hormone in elderly
osteoporotic
women.
Sugimoto T, Nakaoka D and others. Clin Endocrinol (Oxf).
1999 Dec; 51(6): 715-24.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10619976
8 elderly osteoporotic
women mean age 71 years were treated with growth hormone for the
first 4 weeks and subsequently for 48 weeks. Results showed
that treatment caused a significant increase in handgrip and a
decrease in waist/hip ratio. Bone mineral density (BMD)
continued to be monitored after discontinuation of GH treatment
for another 48 weeks, during which significant increases in
radial and lumbar BMD (8.1 and 3.8 % above pre- treatment
values, respectively) were recorded. Results indicate that
GH attenuates the
decrease in muscle strength and bone mass as well as the gain of
abdominal fat with ageing in elderly women.
Two years of treatment with recombinant human growth hormone
increases bone
mineral density in men
with idiopathic
osteoporosis.
Gillberg P, Mallmin H and others. J Clin Endocrinol Metab.
2002 Nov; 87(11): 4900-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12414848
29 men, 27-62 yr old, with
idiopathic [cause unknown] osteoporosis were treated with growth
hormone for 24 months, with a follow-up period of 12 months, and
also received 500 mg calcium and 400 U vitamin D3 daily during
all 36 months. After 2 yr, there was a
4.1% increase in bone
mineral density (BMD) in lumbar spine and 2.6% in total
body. Bone mineral content (BMC) of the total body and
lean body mass increased,
whereas fat mass
decreased. After 36 months, the BMD and BMC in lumbar
spine and total body had increased further.
Low plasma levels of insulin-like growth factor 1 (IGF-I) in
male patients with idiopathic
osteoporosis.
Ljunghall S, Johansson AG and others. J Intern Med.
1992 Jul; 232(1): 59-64.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1640193
In 12 consecutive young to
middle-aged male patients (mean age 46 years, range 30-57 years)
with symptomatic idiopathic [cause unknown] osteoporosis, IGF-I
was significantly lower than in healthy subjects. Conclusions:
Circulating IGF-I could have an important role in maintaining
bone mass, and suggest that impairment of IGF-I production is
involved in the pathogenesis [cause} of osteoporosis.
Insulin-like growth factor I (IGF-I)
stimulates bone turnover in
osteoporosis.
Johansson AG, Lindh E, Ljunghall S. Lancet. 1992 Jun
27; 339(8809): 1619.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1351596
The importance of growth hormone (GH) and GH secretagogues
for bone mass and
density.
Svensson J. Curr Pharm Des. 2002;8(23): 2023-32.
GH stimulates bone
turnover, thereby increasing bone mass and density.
Emerging anabolic treatments for
osteoporosis.
Rosen CJ, Rackoff PJ. Rheum Dis Clin North Am.
2001 Feb; 27(1): 215-33, viii.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11285997
Potential usefulness of
parathyroid hormone and GH/ IGF-I; IGF1 increases remodeling
osteon formation
References-Mental,
Cognitive [Thinking] Decline, Alzheimer’s Disease
A prospective study on circulating insulin-like growth factor
I (IGF-I),
IGF-binding proteins, and
cognitive function in
the elderly.
Kalmijn S, Janssen JA and others. J Clin Endocrinol Metab.
2000 Dec; 85(12): 4551-5.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11134107
Prospective study showed
that higher serum total
IGF-I levels were associated with
less cognitive decline
over the following 2 years. Circulating total IGF-I
levels may reflect an underlying biological process that
influences cognitive decline; (odds per standard deviation
increase = 0.65)
Insulin-like growth factor-I and cognitive function in
healthy older men.
Aleman A, Verhaar HJ and others. J Clin Endocrinol Metab.
1999 Feb; 84(2): 471-5.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10022403
25 healthy older men mean
age 69 years (65-76 years) with well-preserved functional
ability participated in the study. Results showed that
IGF-I levels to
be significantly
associated with the performances (controlled for
education) on the Digit Symbol Substitution test and the Concept
Shifting Task, which measure
perceptual-motor and
mental processing speed. Subjects with
higher IGF-I levels
performed better on these tests, performance on which is
known to decline with aging. In conclusion, the results of this
study support the hypothesis that circulating IGF-I may play a
role in the age-related reduction of certain cognitive
functions, specifically speed of
information processing.
The endocrinology of aging and the
brain.
Lamberts SW. Arch Neurol. 2002 Nov; 59(11): 1709-11
(no abstract on PubMed).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12433255
In healthy elderly men,
IGF-I
significantly associated with
cognition
[thinking], i.e. speed of processing information
Growth hormone in the
brain: characteristics of specific brain targets for the
hormone and their functional significance.
Nyberg F. Front Neuroendocrinol. 2000 Oct; 21(4):
330-48.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11013068
Beneficial effects of
growth hormone on
memory, mental alertness, motivation, and working capacity,
have been reported. Studies also indicated that GH therapy
affects the cerebrospinal fluid levels of various hormones and
neurotransmitters. Further support that the CNS is a target for
GH emerges from observations indicating that the hormone may
cross the blood-brain barrier (BBB) and from studies confirming
the presence of GH
receptors in the brain. Specific binding sites for GH are
present in the choroid plexus, hippocampus, hypothalamus, and
spinal cord. The density of GH binding in the various brain
regions was found to decline with increasing age. The functions
mediated by the GH receptors identified in the hippocampus may
be involved in the hormone's action on memory and cognitive
functions.
Insulin-like growth factor I (IGF-I)
protects cells from apoptosis [death] by
Alzheimer's V642I
mutant amyloid precursor protein through IGF-I receptor in an
IGF-binding protein-sensitive manner.
Niikura T, Hashimoto Y and others. J Neurosci. 2001
Mar 15; 21(6): 1902-10.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11245675
It has been found that
IGF-I
exerts
cytoprotection [cell
protection]
against A-beta
amyloid-induced neuronal [nerve] cell death. Deposits of
A-beta amyloid are one of the pathological hallmarks of
Alzheimer's disease (AD).
Insulin-like growth factor I (IGF-I)
stimulates dendritic [brain
cell connection]
growth in primary somatosensory cortex (Rats).
Niblock MM, Brunso-Bechtold JK, Riddle DR. J Neurosci.
2000 Jun 1; 20(11): 4165-76.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10818152
IGF-I is available to
neurons from multiple sources under independent control.
IGF-I is produced by
many neurons throughout the brain and also by cells in the
cerebral vasculature (brain arteries). IGF-I
increased the branching
and total extent of both apical and basal dendrites
[brain connections]
of pyramidal cells in organotypic slices of rat primary
somatosensory cortex. In addition, IGF-dependent regulation of
dendritic structure may represent a link between age-related
declines in IGF and cognitive [thinking] deficits seen in
senescence.
References-Reports
About Cancer Risks From Growth Hormone/ IGF-I
Growth hormone therapy for adults: not ready
for prime time?
Isley WL. Annals of Internal Medicine. 2002 Aug 6;
137(3): 190-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12160367
There does not
seem to be an increase in
cancer rates in adult patients who have received growth
hormone therapy.
Growth
hormone treatment of children with
brain tumors and risk of
tumor recurrence.
Swerdlow AJ, Reddingius RE and others. J Clin Endocrinol
Metab. 2000 Dec; 85(12): 4444-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11134091
180 children with brain tumors attending three
large hospitals in the United Kingdom and treated with growth
hormone during 1965-1996, and 891 children with brain tumors at
these hospitals who received radiotherapy but not GH.
Thirty-five first recurrences occurred in the GH-treated
children and 434 in the untreated children. The relative
risk of first recurrence
in GH-treated compared with untreated patients, adjusted for
potentially confounding prognostic variables,
was decreased (0. 6; 40%
reduction) as was the relative risk of mortality (0.5; 50%
reduction).
The
significance of serum levels of insulin-like growth factor-1 in
patients with prostate cancer.
Kurek R, Tunn UW and others. BJU Int. 2000 Jan; 85(1):
125-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10619960
238 pts: There
were no significant differences in the mean serum levels of
IGF-I patients with and without prostate cancer (158.6
and 159.1 ng/mL, respectively).
Low
serum insulin-like growth factor 1 (IGF-I): a significant
association with prostate
cancer.
Baffa R, Reiss K and others. Tech Urol. 2000
Sep;6(3):236-9.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10963500
57 patients who underwent radical prostatectomy
[prostate gland removal] (RP) for adenocarcinoma [prostate
cancer]. Serum samples were collected before surgery, 6 months
after surgery, and from 39 age-matched controls. Findings of
this study indicate a
significant association between low serum levels of IGF-I and
prostate cancer.
Plasma
insulin-like growth factor-I and
prostate cancer risk: a
prospective study.
Chan JM, Stampfer MJ and others. Science. 1998 Jan
23;279(5350):563-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9438850
Physicians' Health Study was conducted on
prospectively collected blood from 152 cases of prostate cancer
and 152 controls. A strong
positive association was observed between
IGF-I levels and
prostate cancer risk.
Men in the highest quartile of IGF-I levels had a relative risk
of 4.3 compared with men in the lowest quartile. This
association was independent of baseline prostate-specific
antigen levels.
NOTE:
IGF-I levels in upper quartile were 300-500 with average age of
59 years; in clinical practice, those levels are rarely seen in
men at that age. This was possibly related to lab error because
blood was frozen for up to 15 years before tested. Also note
the opposite results in the previous 2 studies above.
Role of the
insulin-like growth factor family in
cancer development and
progression.
Yu H, Rohan T. J Natl Cancer Inst. 2000
Sep 20;92(18):1472-89.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10995803
High levels of circulating IGF-I and low
levels of IGFBP-3 (binding protein) are associated with
increased risk of several common cancers, including those of the
prostate, breast, colon/ rectum, and lung. [Note: IGFBP-3
usually increases along with IGF-I when growth hormone treatment
is given.]
Insulin-like
growth factors and cancer.
Furstenberger G, Senn HJ. Lancet Oncol. 2002
May;3(5):298-302.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12067807
IGFBPs, [binding proteins] especially IGFBP3,
have independent effects on cell growth; for example, IGFBP3 has
proapoptotic [inducing cell death] activities both dependent on
and independent of p53 [tumor suppression gene]. [Note: IGFBP-3
usually increases along with IGF-I when growth hormone treatment
is given.]
Reciprocal
interactions between the GH axis and
sleep.
Van Cauter E, Latta F and others. Growth Horm IGF Res.
2004 Jun;14
Suppl A:10-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15135771
Decreased total sleep
time and increased sleep fragmentation in growth
hormone-deficient patients as compared with normal controls
Age-related
changes in slow wave
sleep and REM [rapid eye
movement] sleep and relationship with
growth hormone and
cortisol levels in healthy men.
Van Cauter E, Leproult R, Plat L. Journal of the American
Medical Association. 2000 Aug 16;284(7):861-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10938176
149 healthy men, ages 16-83 years showed a
significant decrease in
mean (average) % of deep slow
wave sleep (18.9% during early adulthood, age 16-25
years, to 3.4% during midlife, age 36-50 years) and was replaced
by lighter sleep (stages 1 and 2). The transition from midlife
to late life (age 71-83 years) involved no further significant
decrease in slow wave sleep but an
increase in time awake of 28
minutes per decade at the expense of decreases in both
light non-REM (non-rapid eye movement) sleep (decline of 24
minutes per decade) and REM sleep (decline of 10 minutes per
decade). The decline in slow wave sleep from early adulthood to
midlife was paralleled by
a significant major
decline in growth
hormone (GH) secretion (decline of
372 micrograms per decade).
From midlife to late life, GH
secretion further declined at a slower rate (decline of
43 micrograms per decade).
Independently of age, the amount of
GH secretion was significantly
associated with slow wave sleep.
Interrelationships between
growth hormone and sleep.
Van Cauter E, Copinschi G. Growth Horm IGF Res. 2000
Apr;10 Suppl B:S57-62.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10984255
Extensive
evidence indicates the existence of a consistent relationship
between slow-wave (SW) sleep and increased growth hormone
secretion. There is a linear relationship between the amount of
SW sleep (measured by either visual scoring or spectral analysis
of the EEG [brain wave testing) and the amount of concomitant GH
secretion. During ageing, SW
sleep and GH secretion decrease exponentially and with the same
chronology.
Central
[brain] effects of the somatotropic system.
Schneider HJ, Pagotto U, Stalla GK. European Journal of
Endocrinology. 2003 Nov;149(5):377-92.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14585082
Growth hormone (GH)
and insulin-like growth factor-I (IGF-I)
receptors are expressed
in many brain areas including the hippocampus, pituitary
and hypothalamus. GH and IGF-I can pass the blood-brain barrier
by an as yet not completely understood mechanism. They can also
be produced in the brain and thus act via paracrine/ autocrine
mechanisms. GH and IGF-I are important factors in the
development and differentiation of the CNS [brain and spinal
cord] and have protective
properties in dementia, and in traumatic and ischemic
injury of the CNS. An improvement in cognitive functioning in
GH-deficient patients by GH substitution has been shown.
Significant results could, however, only be achieved with
supraphysiological doses. In some studies, a
correlation between IGF-I and
cognitive function in the
elderly has been found. GH has an important impact on
mood and
well being with GH
secretory capacity being
reduced in depression. Pulsatile GH secretion is closely
related to slow wave sleep (SWS) with SWS being stimulated by GH
releasing hormone and rapid eye movement (REM) sleep by GH.
Age-related
alterations in sleep quality
and neuroendocrine function: interrelationships and
implications.
Blackman MR. JAMA. 2000 Aug 16;284(7):879-81
(letter, no abstract on PubMed).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10938179
References-Immune
System and Growth Hormone/ IGF-I
The
somatogenic hormones and insulin-like growth factor-1 (IGF-I):
stimulators of lymphopoiesis and
immune function.
Clark R. Endocr Rev. 1997 Apr;18(2):157-79
http://edrv.endojournals.org/cgi/content/full/18/2/157#F2
Aging, stress, and nutrition affect blood
concentrations of the anabolic [tissue building]
hormones growth hormone, prolactin, and IGF-I, which in turn
modulate immune
function. Recent studies show that
IGF-I plays an
important role in
the maturation of lymphocytes in bone marrow and assists
their function in the periphery. In rodents, treatment
with IGF-I can restore age-related thymic involution,
increase lymphocyte number and activity and improve
the reduced antibody response to an antigen
challenge, and accelerate lymphoid reconstitution
after radiation and bone marrow transplantation.
Relationship
between plasma IGF-I
levels, in vitro correlates of
immunity, and human
senescence.
Krishnaraj R, Zaks A, Unterman T. Clin Immunol Immunopathol.
1998 Sep;88(3):264-70.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9743613
The NK cell number was positively related to
IGF-I levels in young volunteers but not among elders.
Correlation analysis demonstrated a
highly significant relationship
between plasma IGF-I levels and T-cell (but not B-cell)
proliferative response during
aging (r = 0.492, P < 0.001). Our results imply that
reduced immune system
competence may be one of the consequences of reduced IGF-I
levels in human aging. Among the three types of immune
cells tested, the T-cells were most sensitive to fluctuations in
IGF-I levels. Reduced IGF-I availability may be one of the
determinants of the decline in T-cell-mediated immune function
in the elderly. To our knowledge, this is the
first report presenting
correlative data on concurrent changes in IGF-I levels and
immune parameters in human aging.
Natural immunity and bone and muscle remodeling
hormones in the elderly.
Mariani E, Ravaglia G and others. Mech Ageing Dev. 1998
May 15;102(2-3):279-92.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9720658
Our results stress the importance of nutritional
evaluation in the clinical assessment of elderly people. The
magnitude of the NK [natural
killer] immune response, which constitutes the
first line of defense against
infected and neoplastic [cancer] cells, is
best preserved in oldest-old
people with the best hormonal parameters and nutritional
measures.
Effects of
growth hormone and insulin-like growth factor I (IGF-I)
binding to natural killer cells.
Bidlingmaier M, Auernhammer CJ and others. Acta Paediatr
Suppl. 1997 Nov;423:80-1
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9401547
Human growth hormone (GH) and insulin-like growth
factor I (IGF-I) are known to bind to, and exert modulatory
effects on, different immune competent cells, including natural
killer (NK) cells. NK cells are involved in various actions of
the immune system, including cancer surveillance. Although no
clinically significant defect in tumor or virus defense has been
reported in GH-deficient
patients, the data available indicate
decreased NK cell activity in
these patients. In most studies, the
absolute number and percentage
of NK cells have been found to be normal.
Substitution with GH has been
reported to normalize the decreased NK cell activity in
GH-deficient patients.
Insulin-like growth factor I is an independent coregulatory
modulator of natural killer (NK) cell activity.
Auernhammer CJ, Feldmeier H and others. Endocrinology.
1996 Dec;137(12):5332-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8940354
Supplemental
growth hormone
increases the tumor cytotoxic
[cell killing] activity of natural killer cells in
healthy adults with
normal growth hormone secretion.
Crist DM, Kraner JC. Metabolism. 1990 Dec;39(12):1320-4.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2246974
7 healthy
adults given human growth hormone treatment for 6 weeks, then
crossed-over to the placebo treatment. Results showed that
NK (natural killer) cell
activity was increased within the first week of treatment and
this level was maintained throughout the remaining period
of supplementation.
References-Heart Failure, Cardiomyopathy
[enlarged diseased heart] and Growth Hormone
Growth
hormone treatment in dilated
cardiomyopathy [enlarged, diseased heart].
Perrot A, Ranke MB, Dietz R, Osterziel KJ. J Card Surg.
2001 Mar-Apr;16(2):127-31
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11766830
Serum levels of
IGF-I reflecting growth hormone (GH) secretion are
diminished
in relation to severity of
heart failure in patients with dilated cardiomyopathy.
GH-induced increases of
IGF-I caused notable
improvement of ejection fraction [heart pumping
function]. There is a marked increase in left ventricle [heart
chamber] mass in patients with dilated cardiomyopathy given GH.
Changes in LV mass are related to changes in serum IGF-I
concentrations.
A preliminary
study of growth hormone in the treatment of dilated
cardiomyopathy
[enlarged, diseased heart].
Fazio S, Sabatini D and others. N Engl J Med. 1996 Mar
28;334(13):809-14.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8596546
7 patients given
growth hormone for three months with idiopathic [cause
unknown] dilated [enlarged]
cardiomyopathy [heart muscle disease]
increased
myocardial [muscle] mass
and reduced the size of the left ventricular chamber, resulting
in improvement in hemodynamics
[blood pumping], myocardial energy metabolism,
and clinical status
[symptoms].
Growth hormone
for optimization of refractory
heart failure treatment.
Bocchi EA, Massuda Z and others. Arq Bras Cardiol. 1999
Oct;73(4):391-8.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10754593
63-year-old man with refractory
heart failure given growth
hormone. Results: Left ventricular [chamber]
ejection fraction [blood
pumping] increased from
13 % to 18 % and to 28 % later, in association with reduction of
pulmonary [lung] pressures and
increase in exercise capacity (rise in peak oxygen
consumption). The patient was
"de-listed" for heart transplantation. Growth hormone
may benefit selected patients with refractory heart failure.
Growth hormone prolongs survival
in experimental post infarction [after heart attack]
heart
failure [rats].
Cittadini A, Isgaard J and others. J Am Coll Cardiol.
2003 Jun 18;41(12):2154-63.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12821240
Survival rate was 68% in growth hormone-treated
rats, compared to only 48% in the placebo group,
a significant difference. Growth hormone improved left ventricle
[chamber] relaxation; this was associated with a 50% reduction
in collagen volume fraction and a
27% increase in capillary [very
small arteries] density. Growth hormone
reduced the apoptotic [cell
death] index by 50% at one month and by 33% at 13 months.
References-Diabetes,
Obesity, Metabolic Syndrome and Growth Hormone
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.
Nam SY, Kim KR and others. Int J Obes Relat Metab Disord.
2001 Aug;25(8):1101-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11477493
18 newly diagnosed overweight type 2 diabetic
patients (age 42-56 years, body mass index 28) were given growth
hormone (GH) or placebo for 12 weeks. Results showed that the
fraction of body weight lost as fat was significantly greater
and visceral [in abdomen] fat area was decreased more in the
GH-treated group compared to the placebo-treated group. Lean
body mass and muscle area were reduced in the placebo-treated
group, whereas an increase in both was observed in the
GH-treated group. Glucose disposal was significantly increased
in only the GH-treated group. The GH-induced increase in GDR
was positively correlated with the decrease in the ratio of
visceral fat area to muscle area. Serum glucose and insulin
levels during OGTT (oral glucose tolerance test and HbA-1c
(sugar attached to hemoglobin in red cells) were significantly
decreased after GH treatment. LDL-cholesterol level was
decreased in only the GH-treated group. CONCLUSION:
GH treatment combined with
dietary restriction resulted not only in a decrease of visceral
fat but also in an increase of muscle mass with a consequent
improvement of the insulin resistance observed in obese type 2
diabetic patients.
Growth
hormone and adipocyte [fat cell] function in
obesity.
Nam SY, Marcus C. Horm Res. 2000;53 Suppl 1:87-97.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10895049
In
obesity, growth hormone
(GH) secretion is impaired
which is considered a consequence rather than a cause of
obesity. GH regulates the synthesis of IGF-I in adipocytes [fat
cells]. Increased amounts of IGF-I could be secreted from the
excessively enlarged amounts of adipose tissue. This may
contribute to the normal/high serum-IGF-I in obesity. Favorable
effects of GH treatment have been observed in obese children and
adults. GH treatment
decreases adiposity [fat mass],
reduces triglyceride accumulation by inhibiting lipoprotein
lipase and enhances lipolysis [fat break-down]. GH
treatment also has a favorable effect on obesity-associated
dyslipidemia, but the effects on insulin sensitivity have been
conflicting.
A 9-month,
placebo-controlled study of the effects of
growth hormone treatment
on lipoproteins and LDL
size in abdominally obese men.
Svensson J, Bengtsson BA and others. Growth Horm IGF Res.
2000 Jun;10(3):118-26.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10942632
Thirty men, ages 48-66 years, with a body mass index (BMI) of
25-35 kg/m (2) (overweight) and a waist: hip ratio of >0.95,
received treatment with growth hormone (GH) or placebo for 9
months. The results showed a beneficial
reduction in blood
concentrations of total cholesterol, LDL-C (“bad” type)
and apoB, and marginally increased mean LDL diameter, while
serum Lp (a) increased. The ultimate effect of GH therapy on the
cardiovascular risk remains, however, to be determined.
Growth hormone
treatment of abdominally obese
men reduces
abdominal fat mass,
improves glucose and lipoprotein metabolism, and
reduces diastolic
blood pressure.
Johannsson G, Marin P and others. Clin Endocrinol Metab.
1997 Mar;82(3):727-34.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9062473
(Other results from study above) The most
central findings in both growth
hormone deficiency in adults and the metabolic syndrome are
abdominal/visceral obesity and insulin resistance.
Abdominal obesity is associated with blunted growth hormone (GH)
secretion and low serum insulin-like growth factor-I (IGF-I)
concentrations. GH treatment in GH-deficient adults has
demonstrated favorable effects on most of the features of GH
deficiency in adults, but it is not known whether GH can improve
some of the metabolic aberrations observed in abdominal/visceral
obesity.
30 men, 48-66
yr old, with abdominal/visceral obesity were treated with growth
hormone (GH) in a 9-month randomized, double-blind,
placebo-controlled trial. The results showed that total body
fat, abdominal subcutaneous [under the skin] and visceral
[abdomen] adipose [fat] tissue decreased significantly by 9.2 %,
6.1 %, and 18.1 %, respectively. After an initial decrease in
the glucose disposal rate at 6 weeks, it increased significantly
in the GH-treated group as compared with the placebo-treated
one. The mean (average) total cholesterol and triglyceride
decreased significantly, whereas blood glucose and serum insulin
concentrations were unaffected by the GH treatment. Furthermore,
diastolic blood pressure decreased and systolic blood pressure
was unchanged in response to GH treatment. This trial has
demonstrated that GH can
favorably affect some of the multiple perturbations associated
with abdominal/visceral obesity. This includes a
reduction in
abdominal/visceral obesity, improved insulin sensitivity, and
favorable effects on lipoprotein metabolism and diastolic blood
pressure.
Body
composition, physical exercise,
growth hormone and
obesity.
Weltman A, Weltman JY and others. Eat Weight Disord.
2001 Sep;6(3 Suppl):28-37.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11706505
Growth hormone (GH) secretion is blunted
profoundly in individuals with relative or absolute obesity.
Accumulation of abdominal visceral fat (AVF) particularly
represses GH release.
Administration of GH to obese adults decreases total body fat
and especially AVF. Furthermore, GH supplementation
combined with dietary restriction and/or exercise appears to
enhance favorable changes in body composition. Although exercise
is a powerful stimulus to GH release, the GH response to
exercise is blunted in older and obese individuals. This
suggests that higher relative exercise intensities may be
necessary for exercise alone to stimulate adequate GH release in
obese subjects. Taken as a whole, available data suggest that
GH repletion regimens in
combination with regular exercise and relevant dietary
intervention may provide a tripartite strategy for the
management of significant obesity.
Growth
hormone and the metabolic
syndrome.
Johannsson G, Bengtsson BA. J Endocrinol Invest.
1999;22(5 Suppl):41-6.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10442570
It has been suggested that a critical factor in the association
between obesity, Type 2 diabetes and cardiovascular morbidity is
the mass of intra-abdominal fat.
Striking similarities exist
between the metabolic syndrome and untreated growth hormone (GH)
deficiency in adults. The central findings in both these
syndromes are
abdominal/visceral obesity and insulin resistance. Other
features common to both conditions are
premature atherosclerosis
and increased mortality
from cardiovascular diseases.
These similarities indicate that undetectable and low levels of
GH may be of importance in the metabolic aberrations observed in
both these conditions. Recent investigations have found
that abdominal/visceral distribution of adipose tissue is
associated with endocrine disturbances including increased
activity of the hypothalamic-pituitary [brain]-adrenal axis and
a blunted secretion of GH and sex steroids. Theoretically, these
endocrine perturbations can be a consequence of obesity, but the
endocrine aberrations may have causal effects. We studied
moderately obese, middle-aged men with a preponderance of
abdominal body fat. As a group, they had slight to moderate
metabolic changes known to be associated with abdominal/visceral
obesity. Nine months of GH
treatment reduced their total body fat and resulted in a
specific and a marked decrease in both abdominal subcutaneous
[under the skin] and visceral [abdomen] adipose [fat] tissue.
Moreover, insulin sensitivity
improved and total
cholesterol and triglyceride decreased.
Diastolic blood pressure also
decreased. The finding that GH replacement in men with
abdominal obesity can diminish the negative metabolic
consequences of visceral obesity suggests that
low levels of growth hormone
are of importance for the metabolic aberrations associated with
visceral/abdominal obesity.
References-Tissue
Healing and Growth Hormone
Growth
hormone, burns and
tissue healing.
Lal SO, Wolf SE, Herndon DN. Growth Horm IGF Res. 2000
Apr;10 Suppl B:S39-43.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10984252
Studies on growth hormone
have shown a significant reduction in wound-healing times in
burned patients
References-Erectile
Dysfunction and Growth Hormone
Serum levels
of human growth hormone
during different penile conditions in the
cavernous and systemic blood of healthy men and patients with
erectile dysfunction.
Becker AJ, Uckert S and others. Urology. 2002
Apr;59(4):609-14.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11927337
Strong evidence that growth hormone may be of major importance
in the maintenance of male erectile capability-probably through
a stimulating effect on cyclic guanosine monophosphate
generation in human cavernous smooth muscle-and that a
decline in GH release may
contribute to the manifestation of erectile dysfunction.
Monson John P.
Growth hormone deficiency in adults (chapter 4) in
Comprehensive Clinical Endocrinology 3rd Edition,
Besser and Thorner, eds, (2003, Elsevier), pp 47-56.
Reduced longevity
in untreated patients with isolated
growth hormone deficiency.
Besson A, Salemi S and others. J Clin
Endocrinol Metab. 2003 Aug;88(8):3664-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12915652
