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The following information about Somatopause is for educational use. At California Longevity & Vitality Medical Institute®, we evaluate for Adult Onset Growth Hormone Deficiency. 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.] 

References-Sleep and Growth Hormone 

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