Growing young with HGH references

People on a high carbohydrate diet, diabetics, the obese, the elderly, and chronic fatigue and fibromyalgia sufferers are known to have particularly low Human Growth Hormone (HGH) levels. Adult HGH or GH release tapers off until the master growth hormone is halved at 55, and some 80-year olds and those sufferers may be down to just 10% of healthy HGH levels, which explains their accelerated physical depreciation. HGH secretion is also reduced with disease and poor diet at any age, but it can be brought up; at any rate adequate growth hormone levels are an absolute requirement for cells to grow, repair, and divide, and for you to recover.

The grow young with HGH approach is one of the unexcelled longevity therapies so it's on the Medicine Bag shortlist. Rummage around for l-lysine and arginine pyroglutamate. Colostrum also has the right kind of powerful growth and immune system enhancers, two with one stone again. Take lots.

You'd probably heard about anti-aging with HGH but a series of injections to rejuvenate yourself with it was flat out of reach. For me that would have to be a dire straits decision too, but I've gathered several longevity bio-hacks, foods even, that can reduce age-related decrepitude quite inexpensively at home. The research and the numbers support the method I'm about to detail for anti-aging, or reduced degeneration, followed by considerable youthful recovery. Because HGH is considered the primary youthing hormone, many sages fully expect to see years tacked onto their lifespans when the science is correctly applied. It's hard to say whether you'd need to stack all the supplements that resulted in increased lifespan even on thier own, but it's an eye-opener that such a thing exists, and being youthful well into what should be a declining decade sounds like more fun than not doing it. Most supplements in fact don't help with that that so serve more as a nutritional baseline, but several do, and an HGH increaser is an important bio-hack that sages should be aware of because it can anti-age you in a way the other's can't. I'll try to summarise and follow with the science of anti-aging and bio-hacking by increasing the youthing hormone HGH. 
 

 

Research papers and case studies on fibromyalgia in the HGH references show about 1/3 of FM cases relate to low HGH secretion, which impairs all other growth and recovery including other glandular outputs as well as impairing daily or accumulated damage. One study found that GH secretion was somewhat disturbed, but not as bad as in outright GH deficiency. in other words an undiagnosed and subclinical condition that you can fix may be draining your physical life. A study done in 2000 found no defects in the GH and IGF-1 system in CFS, but others found abnormally low GH response and low nighttime GH output, and a 2001 study also revealed decreased nocturnal hormone values in FM, when high levels are generally secreted for overnight repair. What is not known is whether low GH secretion in CFS and FM is the cause - or the effect - of the disease. What IS known is that since there are no defects in the GH and IGF-1 system, it can be induced to output a little higher with secretagogues such as amino acids, following the Isidori study.

A US doctor with an excellent track record, Paul Cheney, whose clinic specializes in fibromyalgia and chronic fatigue syndrome, uses undenatured whey isolate plus amino acids in addition to a good detoxification program. His work in using the whey follows science that points out that the fatigue portion may be the result of antioxidant pool depletion, particularly glutathione, which is also a crucial part of mitochondrial ATP (energy) production. Anti-aging specialists Dr. Paul White and Dr. Donald McLeod, the past V.P. and president of the American Academy of Anti-aging Medicine of 10,000 members and presently, the Canadian Academy of Anti-aging Medine, point out that dropping 10-20 years from your obvious age is possible, and you can plateau with a 40-something look and fitness level when you're really much older. That would be wonderful for an FM patient, yes?



 

 

Ins and outs of bio-hacking HGH

 

I was kind of dismayed that the local health food stores had a quick run on sublingual human growth hormone HGH and homeopathy as a result of my earlier columns that reviewed increasing HGH for anti-aging and Fat Wars purposes. With all my work, I didn't want anyone to be saying, "I tried that HGH crap -- didn't do nothin' fer me!!" as a result. The straight goods: sublingual HGH and homeopathic formulas do not increase HGH or IGF-1 levels, as the anti-aging specialists and sports nutritionists have found.

The Life Extension approach by Durk and Sandy used 18 grams of amino acids for HGH and nitrogen loading, while the pioneering Isidori Study, downloadable here, details using just two amino acids. While l-arginine and alpha-ketoglutarate used in some commercial formulas were found to compete with l-lysine's metabolic pathway, Isidori showed that arginine pyroglutamate does not compete for the same pathway and is complementary and synergistic with l-lysine. Just 1:1 1200 mg of each triggered the 30 ng/ml IGF-1 needed for the youthful health and repair boost. One company includes this pioneering blend in their own.

 

Kudos from health pros
 

Don Weachter, the nutrition counsellor and microscopist at the largest naturopathic clinic in Eastern Canada: On staff we have a Dr. of Chiropractic, 2 Naturopathic doctors and doctors of acupuncture from China and affiliated is a respected college of massage therapy which teaches a 2-year course. Our clinic sees many chronic pain cases including fibromyalgia.

I have never seen anything as fast and effective as SomaLife gHP for fibromyalgia for many cases. Of course we know all about current practices, treatments, etc, but the Somalife has truly been a blessing for patients, beginning to take effect in as quickly as 2-4 days.

FIBROMYALGIA PERSPECTIVE: Some facts and observations:

● The sleeping period is when we are to produce Growth Hormone in order to repair the normal daily microinjury to tissue.
● Without GH we simply do not heal.
● Fibromyalgia sufferers (all chronic pain sufferers) commonly have poor sleep.
● All tissues, organs, glands etc. will slowly shrink, lose elasticity and function, and age, as GH diminishes with age.
● Women produce GH in the daytime in cycles whereas men do not in much quantity (exceptions include with exercise)
● Women produce considerably less GH at night than men.
● Women have considerably more fibromyalgia, near 100%. (just a coincidence??) These women are age 30+, very rarely younger.
● As we age past age 16, we release less and less GH, as little as 10% of the age 16 capacity by age 60.
● GH is not released when insulin levels are up.
● Insulin is up chronically in much of our society due to high glycemic foods, extra snacking, and other nutritional/lifestyle factors.
● I believe the combination of age, female GH cycles, modern life factors, and failure to gain deep sleep result in the condition often labeled fibromyalgia.
● I look at fibromyalgia as the symptom of accumulation of microinjury to tissue in women over 30, due primarily to suboptimal GH levels.
● I would not hesitate to suggest anyone with chronic pain or injury try SomaLife gHP. It is the only HGH secretogogue with the science based research to show meaningful increases in HGH and IGF in the blood, typically even many 100% increases in 1 hour. 

 


A Word on Discerning between HGH-ish Products
 

Research on anti-aging with HGH has spawned a hundred HGH soundalikes, a few of which produce modest HGH elevations over several weeks but below the threshold for anabolics. Foreign HGH for injectible, oral and sublingual purposes is manufactured by genetically spliced e. coli bacteria, and many doctors will not use it. HGH injections are known to shut down your own HGH production, and oral and sublingual HGH are not absorbed at all, even mixed with sugar. Doctors know the human growth homone soundalikes don't work so they never prescribe oral HGH products. They know that HGH taken orally is simply seen by the digestive system as a very large protein, a 191 amino acid chain in fact, and that it is simply digested like any other large protein. No exceptions on that one.

Even if oral or sublingual HGH was absorbed, four ounces of the highest legal over-the-counter HGH would be required to get an effective daily adult dose. It's not going to happen.

Some products claim to be both a secretagogue and HGH, which of course is impossible. Proteins contained in antler velvet do not increase HGH; they are similarly digested and moreover, products that contain dessicated animal components can contribute pleomorphic nanobacteria, virus, and mycoplasma to the health regime of the hapless consumer. But they do contain some IGF-1, which is a primary product of the HGH and it IS absorbed. You'd need a very lot though. Better than raw antler velvet, raw colostrum contains several bovine growth factors that are a match for all mammals. 

 

Youthful HGH Release . . .
 

As many health professionals quip today, age is a treatable condition. Drs. White and MacLeod said in their workshops that to their knowledge nobody has ever died of old age, but from complications associated with the decrepitude of wasting away, which isn't necessary. HGH increase is about QUALITY of life. If muscle repair, rehabilitation, and energy levels can all keep up, so can the individual. They're thinking, "why taper off at seventy or so when you can do it at 110, 120 or even older", or "if I can maintain this level of fitness I'll be happy". 

That extra fat around the internal organs - the "spare tire" - is a sure sign of HGH deficiency which presents a statistically increased risk of diabetes, heart attack and stroke. But you can increase growth hormone to lose that fat and build lean muscle mass instead. (There are a few other tricks such as chromium-vanadium-manganese minerals and the amino acid l-carnitine to facilitate moving the fats around that may help, and gymnema sylvestris to encourage insulin sensitivity and to regrow the islet cells in the pancreas. In addition, HGH increase will regenerate many other specialized cells including islet cells, kidney cells, liver cells etc....)

HGH references includes research that shows stimulating bone growth in this manner stops the degeneration and risk associated with of osteoporosis. Stimulating growth in skin and underlying tissue tones up the fascia and reduces the wrinkles and sags of age by building collagen. Stimulating growth can repair both leaky gut syndrome and the associated arthritis it often causes. Hormone levels are involved in every process and raising those to youthful values will allow not only faster healing but reduced aging, increased energy and stamina, libido, durability, and muscle tone, and increased organ and tissue quality and enhanced function across the board.

 

Here's more, using Dr. Chein's clinical trials. To be perfectly accurate, Dr. Chein also monitored and adjusted sex hormone levels, so check the Medicine Bag for more on hormone therapy including phenyl-ethylamine, dopamine, pregnenolone, DIM and DHEA. The following is a summary of results of clients who received HGH replacement therapy in Dr. Chein's clinic, prepared in conjunction with his associate Dr. L. Cass Terry, chairman of neurology at the Medical College of Wisconsin in Milwaukee. 

Results have included the following : 

Enhanced memory and mood elevation
Higher energy level
Greater capacity for exercise
Younger skin
Wrinkle removal
Improved cholesterol profiles
Improved cardiac capacity
Improved vision
Heightened sexuality
Improved sleep
Lowered blood pressure
Restoration of vital organs that have shrunk with age
Stronger bones with increased bone mass
Elimination of cellulite
Faster tissue repair and healing of injuries
Restoration of immune system

 

 

Percent of patients reporting improvement

Enhanced muscle strength - 88%
Higher energy levels - 84%
Lengthened exercise endurance - 83%
Expanded exercise tolerance - 81%
Increased muscle mass - 81%
Improved overall sense of well being - 78%
Improved libido/potency - 75%
Improved immune functions - 73%
Decreased body fat without diet - 72%
Firmer skin tone and texture
(Natural face lift as early as 3 months) - 71%
Expanded healing capacity - 71%
Renewed skin thickness - 68%
Revived emotional stability - 67%
Strengthened memory - 62%
Longer duration of penile erection - 62%
Faster healing of injuries - 61%
Reduced hot flashes - 58%
Decreased frequency of nighttime urination - 57%
Renewed healing of old injuries - 55%
Increased back flexibility - 53%
Diminished wrinkles - 51%
Menstrual cycle regulation - 39%
Improved men's hair growth - 38%

 

A Bit on blood pressure and heart disease:

To lower blood pressure naturally you can use amino acids l-lysine and l-proline with hi-dose vitamin C, according to Dr. Linus Pauling and Dr. Matthias Rath's patented cure for heart disease. style. They advocated a b-complex with folate as well. 

L-arginine is very important to the heart muscle. L-arginine breaks down to form l-proline, so the product I use contains arginine pyroglutamate and l-lysine. The aminos help rebuild the scarred artery walls found in atherosclerosis into younger, more flexible tissue, and the flexibility naturally reduces your blood pressure. It increases output from the heart muscle too, and in fact, all the organs and muscles are rejuvenated. Take the aminos with cod liver oil; specifically, DHA and EPA promote flexible tissues. 



 

 

 

HGH references

 Isidori study -- the pioneering study that established the exact form of the compound that triggers HGH release:




HGH Deficiency and Obesity, Diabetes, Cholesterol



In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi

and enter the PMID number to bring up the abstract.

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N Engl J Med 1990 Jul 5;323(1):1-6
PMID: 2355952 [PubMed - indexed for MEDLINE] 

Effects of human growth hormone in men over 60 years old. 

Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE. 

Department of Medicine, Medical College of Wisconsin, Milwaukee. 

BACKGROUND. The declining activity of the growth hormone--insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. METHODS. To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed. 
RESULTS. In group 1, the mean plasma IGF-I level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). There was no significant change in the bone density of the radius or proximal femur. In group 2 there was no significant change in lean body mass, the mass of adipose tissue, skin thickness, or bone density during treatment.
CONCLUSIONS. 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. 

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J Clin Endocrinol Metab. 2002 May;87(5):2018-23.
PMID: 11994335 [PubMed - indexed for MEDLINE] 

Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia.

In conclusion, this genetically homogeneous isolated GH deficient population presents a syndrome characterized by central obesity, dyslipidemia, and elevated systolic blood pressure but reduced cardiac dimensions compared with controls.

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J Clin Endocrinol Metab 2002 Jun;87(6):2725-33
PMID: 12050241 [PubMed - indexed for MEDLINE] 

Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults.

Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E.

Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada M5G 2C4.

BACKGROUND: GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. 

CONCLUSION: GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.

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Clin Endocrinol (Oxf). 2001 Jun;54(6):709-17.
PMID: 11422104 [PubMed - indexed for MEDLINE]

Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement.

CONCLUSIONS: Low-dose GHR improves body composition and QoL as early as 1 month after commencement and the beneficial effects continue at 3 months. Most importantly, these changes occur in the absence of side-effects. We therefore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of age related GH deficiency.

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Am J Kidney Dis. 2001 Jan;37(1 Suppl 2):S115-8.
PMID: 11158875 [PubMed - indexed for MEDLINE]

Can we increase protein synthesis by anabolic factors?

Chronically uremic patients often exhibit a low protein turnover that may increase progressively with the decline of renal function. Thus, anabolic agents can normalize protein metabolism in stable patients without complications, but they should be used carefully in advanced renal failure especially during intercurrent infections.

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Growth Horm IGF Res. 1998 Feb;8 Suppl A:21-3. Review.
PMID: 10993586 [PubMed - indexed for MEDLINE]

Adult vs childhood onset GHD: is there a real clinical difference?

Adults with untreated CO-GHD have significantly lower values for body weight, body mass index, lean body mass and height than those with AO-GHD, while patients with AO-GHD show a more pronounced deviation from normal in psychosocial distress. Following treatment with GH, 12.5 microg/kg/day s.c., patients with AO-GHD showed a decrease in waist/hip ratio and low-density lipoprotein. 

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Am J Physiol Endocrinol Metab. 2002 May;282(5):E1154-62.
PMID: 11934682 [PubMed - indexed for MEDLINE]

Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus.

These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.

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J Endocrinol Invest. 1999;22(5 Suppl):28-32.
PMID: 10442567 [PubMed - indexed for MEDLINE]

Insulin sensitivity in growth hormone (GH)-deficient adults and effect of GH replacement therapy.

Growth hormone (GH) deficiency in adults is characterized by central obesity, dyslipidemia, coagulopathy and glucose intolerance, all features of the "metabolic syndrome", explaining the increased cardiovascular morbidity and mortality associated with GH deficiency in adults. Employing the 2-step euglycemic-hyperinsulinemic clamp, we have demonstrated severe insulin resistance in GH-deficient adults, with a reduction in insulin-mediated glucose utilization of -50%. ...In conclusion, long-term rhGH treatment in GH-deficient adults results in persistent insulin resistance and abnormalities in the GF and GS pathways due to reduced glycogen synthase and hexokinase activities, in the presence of an ongoing reduction of central obesity. We postulate that the insulin resistance is due to chronic rhGH-induced alterations in FFA metabolism, non-physiological levels of IGF-I and chronic basal hyperinsulinemia.

_________________________________________

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12610012&dopt=Abstract

Diabetes Care. 2003 Mar;26(3):625-30.
PMID: 12610012 [PubMed - in process] 

Amino Acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes.

Van Loon LJ, Kruijshoop M, Menheere PP, Wagenmakers AJ, Saris WH, Keizer HA.

Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands. Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, the Netherlands.

CONCLUSIONS-The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal. 

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2118125&dopt=Abstract

Int J Immunopharmacol 1990;12(4):365-71
PMID: 2118125 [PubMed - indexed for MEDLINE] 

Recovery of low thymic hormone levels in cancer patients by lysine-arginine combination.

Mocchegiani E, Cacciatore L, Talarico M, Lingetti M, Fabris N.

Immunology Centre, Gerontology Research Department, Italian National Research Centres on Ageing (INRCA), Ancona, Italy.

Thymic hormones are required for maturation and maintenance of the immune efficiency. It has been previously demonstrated that with advancing age there occurs a progressive reduction of the plasma level of one of the best known thymic peptides, i.e. thymulin, and that the administration of an amino acid combination (lysine-arginine, as present in the commercial preparation Lysargin, Baldacci, Italy) to elderly individuals is able to increase the synthesis and/or release of thymulin to values comparable to those recorded in young subjects. In the present paper we report evidence that cancer patients show much lower thymulin values than those recorded in healthy age-matched individuals and that the oral administration of the amino acid preparation is able to significantly increase thymulin levels even over the values of age-matched controls and to increase the number of peripheral T-cell subsets. It is suggested that such an effect is mediated through the known secretagogue activity of the amino acids on the pituitary release of growth hormone, which has a modulating effect on the thymic endocrine activity. 

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HGH deficiency in heart disease



In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
and enter the PMID number to bring up the abstract.

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J Clin Endocrinol Metab 2002 Mar;87(3):1088-93

The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study.

Colao A, di Somma C, Pivonello R, Cuocolo A, Spinelli L, Bonaduce D, Salvatore M, Lombardi G.

Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, 80131 Naples, Italy. colao@unina.it

Increased cardiovascular morbidity and mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients. ...left ventricular ejection fraction at rest and its response at peak exercise normalized in 60 and 53.3%, respectively, of GH-treated patients and in none of the GH-untreated patients. 

CONCLUSION: 12 months of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports the need of GH replacement in adult GHD patients.

PMID: 11889170 [PubMed - indexed for MEDLINE] 

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Cardiovasc Res 2002 Apr;54(1):25-35

Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system.

Khan AS, Sane DC, Wannenburg T, Sonntag WE.

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.

There is a large body of evidence that biological aging is related to a series of long-term catabolic processes resulting in decreased function and structural integrity of several physiological systems, among which is the cardiovascular system. These changes in the aging phenotype are correlated with a decline in the amplitude of pulsatile growth hormone secretion and the resulting decrease in plasma levels of its anabolic mediator, insulin like growth factor-1 (IGF-1). The relationship between growth hormone and biological aging is supported by studies demonstrating that growth hormone administration to old animals and humans raises plasma IGF-1 and results in increases in skeletal muscle and lean body mass, a decrease in adiposity, increased immune function, improvements in learning and memory, and increases in cardiovascular function. Since growth hormone and IGF-1 exert potent effects on the heart and vasculature, the relationship between age-related changes in cardiovascular function and the decline in growth hormone levels with age have become of interest. ...

Growth hormone has been found to exert potent effects on cardiovascular function in young animals and reverses many of the deficits in cardiovascular function in aged animals and humans. 

Publication Types: 

Review

Review, Tutorial

PMID: 12062358 [PubMed - indexed for MEDLINE] 

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Circulation 2002 Aug 20;106(8):939-44

Comment in: 

Circulation. 2002 Aug 20;106(8):893-5. 

Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study.

Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T.

Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. ajuul@dadlnet.dk

BACKGROUND: Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis.

CONCLUSIONS: Individuals without ischemic heart disease (IHD) but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.

PMID: 12186797 [PubMed - indexed for MEDLINE] 

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J Endocrinol Invest 2002 Jul-Aug;25(7):590-7

Left ventricular diastolic function abnormalities in hypopituitary patients with GH deficiency: evidence for a subclinical cardiomyopathy.

Ozbey N, Sezgil A, Oflaz H, Umman B, Orhan Y, Sencer E, Molvalilar S.

Department of Internal Medicine, Istanbul Faculty of Medicine, Capa, Turkey. nozbey@hotmail.com

The aim of this study was to evaluate cardiac performance, in particular diastolic function, in adult patients with adulthood onset GH deficiency. ...All hormone deficiencies, except for GH, were appropriately replaced in the patients.

CONCLUSION: in adults affected by hypopituitarism, GH deficiency predominantly impairs diastolic function while systolic function at rest is spared. This observation might indicate a preclinical stage of a cardiomyopathy.

PMID: 12150332 [PubMed - in process] 

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Growth hormone and cardiac function.

Ann Endocrinol (Paris). 2000 Feb;61(1):16-21. Review.

PMID: 10790587 [PubMed - indexed for MEDLINE]

The evidence that GH is able to increase cardiac mass suggested its use in the -treatment of chronic heart failure of diverse etiologies. GH administration was demonstrated to induce an improvement in hemodynamics and clinical status in some patients. 

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Am J Hypertens 2002 Sep;15(9):766-72

Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension.

Galderisi M, Caso P, Cicala S, De Simone L, Barbieri M, Vitale G, de Divitiis O, Paolisso G.

Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.

CONCLUSIONS: Free IGF-1 circulating levels are independently associated with coronary flow reserve in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.

PMID: 12219870 [PubMed - in process] 

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Am Heart J 2002 Aug;144(2):359-64

Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.

Adamopoulos S, Parissis JT, Georgiadis M, Karatzas D, Paraskevaidis J, Kroupis C, Karavolias G, Koniavitou K, Kremastinos DT.

Second Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. sadamo@bigfoot.com

BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. 

CONCLUSIONS: GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC.

Publication Types: 

Clinical Trial

Randomized Controlled Trial

PMID: 12177657 [PubMed - indexed for MEDLINE] 

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J Clin Endocrinol Metab 2002 Aug;87(8):3650-5

The cardiovascular risk of GH-deficient adolescents.

Colao A, Di Somma C, Salerno M, Spinelli L, Orio F, Lombardi G.

Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples, 80131 Naples, Italy. colao@unina.it

To investigate the onset of the cardiovascular impairment in patients with GH deficiency (GHD), we prospectively studied cardiovascular risk parameters, cardiac mass and performance (by echocardiography)...

CONCLUSION: GH discontinuation is inappropriate in adolescents with severe GHD, inducing impairment of lipid profile and cardiac morphology and performance. Because the results on the cardiovascular system and on the lipid profile were suboptimal, it is likely that the GH dose in severe GHD adolescents should be higher.

PMID: 12161490 [PubMed - indexed for MEDLINE]

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J Am Coll Cardiol 2002 Apr 3;39(7):1175-81

Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure.

Hambrecht R, Schulze PC, Gielen S, Linke A, Mobius-Winkler S, Yu J, Kratzsch J J, Baldauf G, Busse MW, Schubert A, Adams V, Schuler G.

University of Leipzig-Heart Center, Department of Cardiology, Leipzig, Germany. hamr@medizin.uni-leipzig.de

OBJECTIVES: We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF. BACKGROUND: Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown. 

CONCLUSIONS: In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.

PMID: 11923043 [PubMed - indexed for MEDLINE] 

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Clin Endocrinol (Oxf) 2001 Dec;55(6):741-8

Low individualized growth hormone (GH) dose increased renal and cardiac growth in young adults with childhood onset GH deficiency.

Link K, Bulow B, Westman K, Salmonsson EC, Eskilsson J, Erfurth EM.

Department of Endocrinology and Diabetology, University Hospital Lund, Sweden.

OBJECTIVE: In childhood onset GH deficiency (GHD) a reduction in left ventricular mass (LV-mass) and impairment of systolic function as well an impairment in glomerular filtration rate (GFR) has been shown. The aim of the present study was to assess if a low GH dose resulted in an improvement in morphological and functional parameters of these organs. 

CONCLUSION: A low individualized GH dose to adults with childhood onset GHD resulted in an increase in LV-mass index and kidney length. Re-establishing GH treatment with a low dose in this patient group can lead to a further somatic maturation of these organs, probably not accomplished previously.

PMID: 11895215 [PubMed - indexed for MEDLINE] 

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Johannsson G, Bengtsson BA.

Growth hormone and the metabolic syndrome.
J Endocrinol Invest. 1999;22(5 Suppl):41-6. Review.

Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

The association of several risk factors, obesity, dyslipoproteinemia, hepatic steatosis, insulin resistance and hypertension with Type 2 (non-insulin-dependent) diabetes mellitus and myocardial infarction has long been known and has been termed the "metabolic syndrome". In 1988 Reaven introduced syndrome X as the link between insulin resistance and hypertension. It has been suggested that a critical factor in the association between obesity, Type 2 diabetes and cardiovascular morbidity is the mass of intraabdominal 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-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 and visceral adipose tissue. Moreover, insulin sensitivity improved and serum concentrations of 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 this hormone are of importance for the metabolic aberrations associated with visceral/abdominal obesity.

PMID: 10442570 [PubMed - indexed for MEDLINE] 

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HGH and IGF-1 Therapy in Arthritis



In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
and enter the PMID number to bring up the abstract.

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Life Sci. 2002 May 31;71(2):139-51.
PMID: 12031684 [PubMed - indexed for MEDLINE]

GH administration and renal IGF-I system in arthritic rats.

Ibanez de Caceres I, Priego T, Martin AI, Lopez-Calderon A, Villanua MA. 

CONCLUSION: These data suggest that experimental arthritis causes renal dysfunction and GH treatment can ameliorate this effect.

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J Bone Joint Surg Br 2002 Mar;84(2):276-88 Related Articles, Links
PMID: 11922373 [PubMed - indexed for MEDLINE] 

Insulin-like growth factor-I enhances cell-based repair of articular cartilage.

Fortier LA, Mohammed HO, Lust G, Nixon AJ.

Cornell University College of Veterinary Medicine, Ithaca, New York 14853, USA.

Gross filling of defects was improved, and the tissue contained a higher proportion of cells producing type-II collagen. Measurements of collagen type II showed improved levels in IGF-I-treated defects, supporting in situ hybridisation and immunohistochemical assessments of the defects. IGF-I improves the repair capabilities of chondrocyte-fibrin grafts in large full-thickness repair models.

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Gene Ther 2001 Oct;8(19):1443-9 Related Articles, Links
PMID: 11593356 [PubMed - indexed for MEDLINE] 

Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation.

Madry H, Zurakowski D, Trippel SB.

Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. 

These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage.

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J Orthop Res 2001 Jul;19(4):720-8 Related Articles, Links
PMID: 11518284 [PubMed - indexed for MEDLINE] 

Insulin-like growth factor-I gene expression patterns during spontaneous repair of acute articular cartilage injury.

Fortier LA, Balkman CE, Sandell LJ, Ratcliffe A, Nixon AJ.

Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

This study evaluated the constitutive insulin-like growth factor-I (IGF-I) gene expression pattern in spontaneously healing cartilage defects over the course of 16 weeks, and correlated the tissue morphology and matrix gene expression with IGF-I mRNA levels. 

In conclusion, this study demonstrated that the spontaneous healing of articular defects was accompanied by a temporal fluctuation in IGF-I gene expression which was discoordinate to the steady rise in expression of cartilage matrix molecules such as procollagen type II.

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J Rheumatol 2001 Jan;28(1):29-34
PMID: 11196538 [PubMed - indexed for MEDLINE] 

Association between insulin-like growth factor status and physical activity levels in rheumatoid arthritis.

Lemmey A, Maddison P, Breslin A, Cassar P, Hasso N, McCann R, Whellams E, Holly J.

CONCLUSION: Our results indicate that the reduction in circulating IGF proteins observed in our patients is more related to their sedentary lifestyle than to the inflammatory process. This conclusion is in agreement with reports that show that highly active individuals typically exhibit higher levels of systemic IGF proteins than age matched sedentary controls.

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J Orthop Res 2001 Jan;19(1):11-7
PMID: 11332605 [PubMed - indexed for MEDLINE] 

The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I.

Bonassar LJ, Grodzinsky AJ, Frank EH, Davila SG, Bhaktav NR, Trippel SB.

Orthopaedic Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.

Articular cartilage is routinely subjected to mechanical forces and to cell-regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial fluid that is anabolic for cartilage. 

Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells. 

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HGH deficiency in neurodegenerative disorders



In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi and enter the PMID number to bring up the abstract.

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IGF-1 May Stimulate Brain Function

If grandpa's been "slipping" a bit in his twilight years, it may be that he's lacking the hormones he needs to keep his brain functioning efficiently. 

Researchers in the Netherlands measured insulin-like growth factor 1 (IGF-1) levels in a group of healthy older men aged 69-76, and evaluated their performance on a battery of tests designed to measure cognitive ability. IGF-1 mediates the stimulatory effect of growth hormone (GH) on tissues, and also triggers its own anabolic effects. Age-related decline of IGF-1 is associated with the breakdown of muscle and bone mass, increased body fat, and other types of physiological degeneration. 

The investigators in this study found a positive correlation between IGF-1 levels and perceptual motor and mental processing speed - a relationship independent of both education level and age. The implications are important because they signify a possible relationship between hormone levels and "the rate at which cognitive operations can be executed in the brain." 

"This finding suggests that the GH/IGF-1 axis may play a role in the age-related decline of certain cognitive functions," researchers concluded. Results bolster previous studies linking growth-hormone deficiency with cognitive and memory impairment in both children and adults. 

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J Neuropathol Exp Neurol 2000 Jul;59(7):575-84
PMID: 10901228 [PubMed - indexed for MEDLINE] 

Insulin-like growth factor-I promotes myelination of peripheral sensory axons. 

Russell JW, Cheng HL, Golovoy D. 

Department of Neurology, Veterans Administration Medical Center, University of Michigan, Ann Arbor 48109, USA. 

BACKGROUND: Insulin-like growth factor-I (IGF-I) in vivo or in the presence of other permissive factors can promote myelination in the central nervous system. 
CONCLUSIONS: IGF-I is important in myelination and is critical not only for initial SC ensheathment of the axon and upregulation of myelin proteins, but also for sustained myelination. Furthermore, IGF-I associated axonal size is not the sole determinant for myelination. 

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Ann N Y Acad Sci 1999 Sep 14;883:124-30
PMID: 10586238 [PubMed - indexed for MEDLINE] 

IGF-I promotes peripheral nervous system myelination. 

Cheng HL, Russell JW, Feldman EL. 

Department of Neurology, University of Michigan, Ann Arbor 48109-0588, USA. 

Insulin-like growth factor-I (IGF-I) promotes the proliferation and differentiation of Schwann cells (SC). Continued IGF-I exposure leads to enhanced P0 expression and long-term myelination. No myelination occurs in the absence of IGF-I. These data imply that IGF-I is critical not only for SC attachment and ensheathment of axons but also for long-term myelination. 

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Neuroreport 1997 Sep 8;8(13):2871-6
PMID: 9376522 [PubMed - indexed for MEDLINE] 

The insulin-like growth factors I and II stimulate proliferation of different types of Schwann cells. 

Sondell M, Fex-Svenningsen A, Kanje M. 

Department of Animal Physiology, Lund University, Sweden. 

IGF-II enhanced proliferation of Schwann cells surrounding unmyelinated nerve fibres. In contrast, truncated IGF-I promoted proliferation of Schwann cells of myelinated nerve fibres while insulin increased proliferation of both cell types. 

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J Neurobiol 1999 Dec;41(4):540-8 Related Articles, Links
PMID: 10590177 [PubMed - indexed for MEDLINE] 

Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells. 

Delaney CL, Cheng HL, Feldman EL. 

Department of Neurology, University of Michigan, 200 Zina Pitcher Place, 4414 Kresge III, Ann Arbor, Michigan 48109, USA. 

BACKGROUND: Both neurons and glia succumb to programmed cell death (PCD) when deprived of growth factors at critical periods in development or following injury. Insulin-like growth factor-I (IGF-I) prevents apoptosis in neurons in vitro. 
CONCLUSIONS: These results suggest that IGF-I rescues Schwann Cells from apoptosis via PI 3-K signaling which is upstream from caspase activation. Copyright 1999 John Wiley & Sons, Inc. 

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Neurology 1997 Dec;49(6):1621-30
PMID: 9409357 [PubMed - indexed for MEDLINE] 

Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group. 

Lai EC, Felice KJ, Festoff BW, Gawel MJ, Gelinas DF, Kratz R, Murphy MF, Natter HM, Norris FH, Rudnicki SA. 

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. 

Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects. 

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Pharmacoeconomics 1999 Feb;15(2):179-95

Cost effectiveness of recombinant human insulin-like growth factor I therapy in patients with ALS. 

Ackerman SJ, Sullivan EM, Beusterien KM, Natter HM, Gelinas DF, Patrick DL. 

Covance Health Economics and Outcomes Services Inc., Washington, DC, USA. stacey.ackerman@covance.com

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterised by a progressive loss of voluntary motor activity. Recombinant human insulin-like growth factor I (rhIGF-I) has been shown to be useful in treating ALS. 
CONCLUSIONS: Treatment with rhIGF-I is most cost effective in ALS patients who are either in earlier stages of the disease or progressing rapidly. The cost effectiveness of rhIGF-I therapy compares favourably with treatments for other chronic progressive diseases. 

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HGH Deficiency in Osteoporosis



In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi and enter the PMID number to bring up the abstract.

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Celiker R, Arslan S.

Comparison of serum insulin-like growth factor-1 and growth hormone levels in osteoporotic and non-osteoporotic postmenopausal women.
Rheumatol Int 2000;19(6):205-8
PMID: 11063288 [PubMed - indexed for MEDLINE] 

Hacettepe University School of Medicine, Department of Physical Medicine and Rehabilitation, Ankara, Turkey. celiker@tr-net.net.tr

BACKGROUND: The purpose of this study was to compare the insulin-like growth factor-1 (IGF-1) levels and the growth hormone (GH) levels in osteoporotic and non-osteoporotic postmenopausal women. 

CONCLUSIONS: When compared with normal postmenopausal women, IGF-1 levels were found to be lower in women with osteoporosis. IGF-1 seems to play an important role in the development of low bone mass and the present results suggest that IGF-1 is a useful predictor of the presence of osteoporosis.

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Monson JP, Drake WM, Carroll PV, Weaver JU, Rodriguez-Arnao J, Savage MO.

Influence of growth hormone on accretion of bone mass.
Horm Res 2002;58 Suppl 1:52-6
PMID: 12373015 [PubMed - in process] 

Department of Endocrinology, St Bartholomew's Hospital, London, UK.

Growth hormone (GH) exerts important influences on bone metabolism during lifespan. During childhood, GH is a major determinant of acquisition of bone mass and in adult life, GH partly determines the rate of bone remodelling and therefore influences maintenance of bone mineral density. GH replacement in adult-onset GH deficiency results in an early increment in indices of bone remodelling which persists for up to 5 years.

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Sugimoto T, Nakaoka D, Nasu M, Kanzawa M, Sugishita T, Chihara K.

Effect of recombinant human growth hormone in elderly osteoporotic women.
Clin Endocrinol (Oxf) 1999 Dec;51(6):715-24
PMID: 10619976 [PubMed - indexed for MEDLINE]

Third Division, Department of Medicine, Kobe University School of Medicine, Kobe, Japan.

OBJECTIVE: Bone mineral density and growth hormone (GH) secretion rate both decline during normal human aging. We evaluated the effects of recombinant human GH on markers of body composition and bone turnover in an open study in 8 elderly osteoporotic women aged 68-75 years (mean age 71 years). 

CONCLUSION: These results indicate that GH attenuates the decrease in muscle strength and bone mass as well as the gain of abdominal fat with aging in elderly women. The present data provide useful information about the application of GH treatment in elderly women.

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Sugimoto T, Kaji H, Nakaoka D, Yamauchi M, Yano S, Sugishita T, Baylink DJ, Mohan S, Chihara K.

Effect of low-dose of recombinant human growth hormone on bone metabolism in elderly women with osteoporosis.
Eur J Endocrinol 2002 Sep;147(3):339-48
PMID: 12213671 [PubMed - in process] 

Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

BACKGROUND: There has been increasing evidence that the growth hormone (GH)-IGF-I axis plays an important part in the maintenance of bone mass. However, controversy still exists as to the effect of GH treatment on bone mineral density in elderly patients with osteoporosis.

CONCLUSIONS: Low-dose GH treatment attenuated the decrease in muscle strength and bone mass in elderly women without side effects, although changes in nutrition and exercise might affect BMD. The present findings provide useful information regarding the use of low-dose GH treatment in elderly women with osteoporosis.

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Attie KM.

The importance of growth hormone replacement therapy for bone mass in young adults with growth hormone deficiency.
J Pediatr Endocrinol Metab 2000 Sep;13 Suppl 2:1011-21
PMID: 11086656 [PubMed - indexed for MEDLINE] 

Department of Medical Affairs, Genentech, Inc., South San Francisco, CA 94080, USA. kma@gene.com

GH deficiency (GHD) is associated with reduced bone turnover and decreased bone mineral density (BMD), especially in patients with childhood-onset GHD. GH replacement therapy stimulates bone remodeling and causes an initial decrease in BMD due to bone resorption and expansion of the remodeling space. This is followed by increased bone formation and a significant increase in BMD that continues with prolonged GH therapy. 

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Bex M, Abs R, Maiter D, Beckers A, Lamberigts G, Bouillon R.

The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial.
J Bone Miner Res 2002 Jun;17(6):1081-94
PMID: 12054164 [PubMed - in process] 

Department of Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium.

BACKGROUND: Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. 

CONCLUSION: A significant increase in spine BMC (bone mineral content) and BMD (bone mineral density) and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period. 

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HGH Deficiency in Fibromyalgia (FM)



Robert Bennett's web site is www.myalgia.com

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Human Growth Hormone is the Treatment that Does the Most!

Bennett RM, Clark SC, Walczyk J. A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. Am J Med 1998 Mar;104(3):227-31 Department of Medicine, Oregon Health Sciences University, Portland 97201, USA.

PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH) secretion, occur in about one third of patients who have many clinical features of growth hormone deficiency, such as diminished energy, dysphoria, impaired cognition, poor general health, reduced exercise capacity, muscle weakness, and cold intolerance. To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, we assessed the clinical effects of treatment with growth hormone. 

CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels experienced an improvement in their overall symptomatology and number of tender points after 9 months of daily growth hormone therapy. This suggests that a secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia.

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Fibromyalgia patients have dysfunctional Growth Hormone Release!

Bennett RM, Cook DM, Clark SR, Burckhardt CS, Campbell SM. Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. J Rheumatolo 1997 Jul; 24(7): 1384-9

OBJECTIVE: To investigate the serum levels of insulin-like growth factor-I (IGF-I) in patients with fibromyalgia (FM) compared to healthy controls and patients with other rheumatic diseases, and to explore possible etiologic mechanisms of low IGF-I levels inpatients with FM. 

CONCLUSION: Many, but not all, patients with FM have low levels of IGF-I that cannot be explained by clinical associations. These results suggest that low IGF-I levels in patients with FM are a secondary phenomenon due to hypothalamic-pituitary-GH axis dysfunction.

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Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology. 

AUTHORS: Bennett RM

AUTHOR AFFILIATION: Dept. Medicine (L329A), Oregon Health Sciences University, Portland 97201, USA. 

SOURCE: Z Rheumatol 1998;57 Suppl 2:72-6

CITATION IDS: PMID: 10025088 UI: 99149227

Growth hormone (GH) deficiency occurs in about 30% of fibromyalgia patients. Treatment of GH deficient fibromyalgia patients with recombinant growth hormone improves several clinical features, including the tender point count. Defective GH secretion in these patients appears to be due to increased somatostatin tone in the hypothalamus. An hypothesis is presented which relates dysfunctional GH secretion to the effects of intermittent hypercortisolemia on upregulating the density of beta-adrenergic receptors in the hypothalamus. The resulting augmentation of beta-adrenergic tone stimulates the release of somatostatin, thus, impairing GH secretion. 

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The Growth Hormone (GH)-Releasing Hormone - GH - Insulin-like Growth Factor-1 Axis in Patients with Fibromyalgia Syndrome*

A. Leal-Cerro, J. Povedano, R. Astorga, M. Gonzalez, H. Silva, F. Garcia-Pesquera, F. F. Casanueva, and C. Dieguez

Department of Endocrinology (A.L.-C., R.A., H.S., F.G.-P.) and Reumatology (J.P., M.G.), Hospital Universitario "Virgen del Rocio", 15700 Sevilla; and Departments of Medicine (F.F.C.) and Physiology (C.D.), Complejo Hospitalario Universitario and Faculty of Medicine, University of Santiago, 15700 Santiago de Compostela Spain

Received September 30, 1998. Revised May 24, 1999. Accepted June 1, 1999. 

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. 

CONCLUSION: our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM. (The Journal of Clinical Endocrinology & Metabolism 84: 3378-3381, 1999) 

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Secretion of growth hormone in patients with chronic fatigue syndrome.

Growth Horm IGF Res 1998 Apr;8 Suppl B:127-9

Berwaerts J, Moorkens G, Abs R
Department of Endocrinology, Middelheim Hospital, Antwerp, Belgium.

PMID: 10990147, UI: 20443554

Decreased serum levels of insulin-like growth factor I (IGF-I) are common in patients with fibromyalgia, which is frequently associated with chronic fatigue syndrome (CFS). 

Twenty patients with CFS (7 men, 13 women; age range, 30-60 years) and age- and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of IGF-I were also measured. Serum IGF-I SDS (+/- SD) was significantly lower in patients with CFS than in controls (SDS, -0.39 +/- 1.07 vs 0.33 +/- 0.84; P = 0.02). 

Patients with CFS also tended to have reduced nocturnal secretion of GH (area under the curve, 32.4 +/- 18.3 vs 62.7 +/- 43.7 microg/l/15 minutes; P= 0.06), but peak GH responses to insulin-induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition. 

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Growth Hormone Eases Fibromyalgia PainImproves Stiffness, Reduces Number of Tender Points

June 27, 2002 -- For anyone with fibromyalgia, effective treatment is elusive and the quest is frustrating. Research has shown that the illness may be due to low levels of growth hormone. And now, new research shows that growth hormone injections can relieve the pain and stiffness that comes with fibromyalgia. 

Fibromyalgia is a chronic disorder that causes pain all over the body with muscle and joint stiffness. If affects mostly women and is diagnosed by identifying specific tender points on the body. These areas are particularly tender to touch - even to light touch. Although the definite cause of fibromyalgia is unknown, one theory is that it may be caused by below-normal levels of growth hormone. Growth hormone deficiency has been associated with low energy, muscle weakness, sensitivity to cold, weakened ability to remember and think, and other problems - many of which are seen in people with fibromyalgia. 

This illness definitely has a hormone component, Alfonso Leal-Cerro, MD, tells WebMD. Leal-Cerro presented new findings at the annual meeting of The Endocrine Society. He is a professor of endocrinology at the Hospital Universitario Virgen del Rocio in Seville, Spain. "We had previously found that a high number of patients with fibromyalgia have low levels of insulin-like growth factor 1," he says. Growth hormone increases the level of insulin-like growth factor 1 (IGF-1) in the body. So Leal-Cerro and colleagues set out to see if giving growth hormone could help people suffering from fibromyalgia. Giving growth hormone should increase the levels of IGF-1. 

Pharmacia donated the growth hormone that was used in the study, and one of the co-authors, Angels Ulied, is a staff researcher at Pharmacia in Barcelona, Spain. In this small study, he and colleagues followed 20 women with both fibromyalgia and low levels of IGF-1. Each woman received injections of either growth hormone or placebo. For six months, neither the women nor the researchers knew whether the women were receiving growth hormone or the placebo. Then, for the next 12 months, all the women were knowingly treated with growth hormone. 

After six months of treatment, the women that received the growth hormone injections had significantly less morning stiffness and pain and fewer tender points than at the beginning of treatment. The women continued to see these benefits at 12 months. The placebo group had significantly less morning stiffness and fewer tender points but had no significant reduction in pain. Leal-Cerro said that he and colleagues are next planning to study treating fibromyalgia with an oral drug that increases production of growth hormone. 

"Fibromyalgia is a frustrating disease for people who live with it, and they are desperate for effective treatment," Clifford J. Rosen, MD, tells WebMD. He was not involved in the study. "The people in the study were probably quite disabled with their disease, because their IGF-1 levels were quite low, and there is a body of literature that shows IGF-1 levels are lower in fibromyalgia than in the general population. This deficiency may contribute to the stiffness in fibromyalgia," says Rosen, staff endocrinologist at the University of Maine and St. Joseph's Hospital in Bangor, Maine. Rosen is the president-elect of the American Society of Bone and Mineral Research, and his research has focused on growth hormone, IGF-1, and the relation of these substances to bone growth. "However, I think it's too early to know if this is a feasible approach." 

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(c) 2002 WebMD Inc.Hakkinen K, Pakarinen A, Hannonen P, et al. Effects of strength training on muscle strength, cross-sectional area, maximal electromyographic activity, and serum hormones in premenopausal women with fibromyalgia. J Rheumatol. 2002 Jun;29(6):1287-1295.

OBJECTIVE: To examine the effects of strength training on basal concentrations and acute responses of serum hormones, and their possible interrelationships with training induced muscle hypertrophy and strength gains of the knee extensor muscles in women with fibromyalgia(FM) and healthy controls. 

CONCLUSION: Both the magnitude and timecourse of adaptations of the neuromuscular system to resistance training in women with FM were completely comparable to those taking place in healthy women. Basal levels of the anabolic hormones seem to be similar in women with FM compared to age matched healthy women. Observations recorded during the acute loading conditions might be considered an indication of the training induced adaptation of the endocrine system, showing that the acute GH response may become systematic after strength training in both women with FM and controls. 

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Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

Clin Endocrinol (Oxf). 2000 Jul;53(1):99-106.

PMID: 10931086 [PubMed - indexed for MEDLINE]

CONCLUSIONS: We observed a significant impairment of GH response during insulin-induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF-I. The clinical expression of this inadequate GH secretion can thus be questioned, although the alteration in body composition may be related to this relative GH deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are required in order to identify specific adaptations within the neurotransmitter system in CFS and to determine the clinical importance of the impaired GH homeostasis. 

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ENDO: Fibromyalgia Responds to Growth Hormone Treatment

By Paula Moyer

Special to DG News

SAN FRANCISCO, CA -- June 20, 2002 -- Patients with fibromyalgia get relief from many of their symptoms when they are treated with growth hormone therapy.

"This illness definitely has an endocrine component," said Alfonso Leal-Cerro, MD, who presented these findings at the 84th annual meeting of the Endocrine Society. 

"We had previously found that a high number of patients with fibromyalgia have low levels of insulin-like growth factor-1 [IGF-1]," explained Dr. Leal-Cerro, lead investigator on the study and professor of endocrinology at the Hospital Universitario Virgen del Rocio in Seville, Spain. "Therefore, we wanted to see if growth hormone administration would be effective at addressing their symptoms." 

His team randomised 20 women with both fibromyalgia and IGF-1 lower than 125 ng/mL to injections of growth hormone (GH) or to placebo in a double-blind fashion. After six months, they entered an open label phase for 12 months. The treatment group received an initial GH dose of 0.13 mg/day (0.4 IU); the dose could be titrated up to .66 mg (2 IU) daily. The women assessed their morning stiffness and pain, andfibromyalgic tender points at baseline and at 3, 6, 9, and 12 months of treatment. Weight and waist-to-hip ratios were also obtained, and patients responded to a general quality-of-life questionnaire.

The treatment group had sustained elevations of IGF-1 levels throughout the study and reported significantly less morning stiffness and pain at six months than at baseline (p<0.02 and p<0.04, respectively). The treatment group also had fewer fibromyalgic tender points than controls (p<0.04). These results continued at 12 months (p<0.05 for stiffness, p<0.01 for pain, p<0.01 for tender points).

The placebo group had significantly less morning stiffness and fewer fibromyalgic tender points at six and 12 months than at baseline (p<0.05), but experienced no significant reduction in pain. The groups had no differences in weight, waist-to-hip ratios, or scores on the quality-of-life questionnaire.

The results suggest that a secondary growth hormone deficiency may be responsible for some symptoms of fibromyalgia, the investigators concluded. Dr. Leal-Cerro said that he and colleagues are next planning to study the efficacy of treating fibromyalgia with a GH secretagogue, which would be administered orally.

Pharmacia donated the growth hormone that was used in the study, and one of the co-authors, Angels Ulied, is a staff researcher at Pharmacia in Barcelona, Spain. 

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Laurie Barclay, M.D. 

NEW YORK

Source: Arthritis Rheum. 2002;46(5):1344-1350. Reviewed by Gary D. Vogin, MD

(MedscapeWire) May 06 — Growth hormone (GH) response to maximal exercise is impaired in patients with fibromyalgia, according to research reported in the May issue of Arthritis & Rheumatism. Normalization with pyridostigmine pretreatment suggests a defect in somatostatin tone, which may be related to the exhaustive stage of chronic stress. 

"The results of this study indicate that GH deficiency is probably more common in fibromyalgia patients than was originally reported," senior author Robert Bennett, MD, MRCP, from Oregon Health Sciences University in Portland, says in a news release. 

Fibromyalgia is thought to be a stress-related syndrome, linked to malfunctions of the hypothalamic, pituitary, and adrenal hormones, including GH. 

In this study, 20 women with fibromyalgia and a control group of 10 healthy women exercised to volitional exhaustion, reaching maximum respiratory and pulse rate on a treadmill. One month later, testing was repeated 1 hour after pretreatment with pyridostigmine, which inhibits somatostatin secretion. 

Without pyridostigmine pretreatment, 11 of the 20 patients with fibromyalgia had no exercise-induced increase in GH levels. After the administration of pyridostigmine, 19 of the 20 patients had a normal GH response to exercise. 

The overall increase in GH was 8 times higher than without pretreatment and was similar to that seen in controls. Pyridostigmine alone did not stimulate GH secretion in patients with fibromyalgia, nor did it affect GH levels in controls. Even those fibromyalgia patients with normal insulin-like growth factor 1 levels had an impaired GH response to exercise. 

"Recognition of defective GH secretion in fibromyalgia patients is of some practical relevance because GH replacement therapy was shown to benefit fibromyalgia patients in a 9-month placebo-controlled study," Bennett says. 

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HGH and IGF-1 Do Not Contribute To Cancer

In a preliminary study conducted by June Chan at the Harvard School of Public Health, published in the prestigious Journal of Science January 23, 1998, IGF-1 was linked to a higher incidence of prostate cancer. The implication of this study was that men with a high PSA blood level or a strong family history of prostate cancer should think twice before starting growth hormone or growth hormone releasing agents. Of course, this would also mean IGF-1 or IGF-1 producing agents. 

In the summer issue of the International Journal of Antiaging Medicine 1998 premier issue, Dr. L. Cass, M.D., Ph.D., Pharm.D., Medical College of Milwaukee, Wisconsin, and chief medical advisor to Cenegenics published a paper entitled “Insulin-Like Growth Factor-1 blood levels are not associated with prostate specific antigen (PSA) levels or prostate cancer a study of 749 men”. The incidence of prostate cancer increases with age in men whereas blood levels of IGF-1 decline significantly with age, at about 14% per decade after the age of 30. Therefore, it seems unlikely that IGF would have any causative relationship with prostate cancer. However, the question does arise that with supplementation with recombinant human growth hormone can it actually pose a risk for increased prostate cancer? The question also arises that IGF-1, if given as a supplement, would it do the same? 

The purpose of the study conducted by Dr. Cass was to determine the IGF blood levels in men receiving recombinant growth hormone supplementation as a relationship to blood PSA levels as an indicator of prostate cancer. In this particular study as well as three others, circulating IGF-1 levels had no relationship to PSA levels or prostate cancer and did not appear to be a risk factor in patients with or without recombinant growth hormone administration. These findings are consistent with extensive studies on recombinant growth hormone replacement in growth hormone deficient adults resulting from pituitary or prepituitary tumors. Moreover, no increase in prostate cancer or any other malignancy was observed in approximately 3,000 patients during long term treatment with recombinant growth hormone. 

Thus to date, the weight of scientific evidence shows that recombinant growth hormone or IGF-1 do not cause prostate cancer. Certainly more long term studies are essential to assess the benefits and risks of life long growth hormone replacement or IGF-1 supplementation. If anything, the tendency is that recombinant growth hormone and IGF-1 actually reduce the incidence of prostate cancer and PSA readings that are greater than 4, as evidenced by the results of this particular study. 

In his book entitled Grow Young with HGH Dr. Ronald Klatz, president of the American Academy of Antiaging Medicine, reported on the patients treated by Drs. Chein and Terry with human growth hormone injections. Of 800 patients the only side effects that had been reported were minor joint aches and pains and some fluid retention. These symptoms disappeared in the first couple of months. 

More significantly was the fact that there were no reported cases of cancer among all 800 patients treated at their clinic. It is very reassuring since some investigators have been concerned that growth hormone would cause undetected cancer cells to divide more rapidly. 

Even so, you would think with 800 people over the age of 40-years-old, given the normal incidence of cancer, some of these people would certainly get the disease. It could be that there is some sort of protective effect of growth hormone replacement, probably through the immune system. 

Even more compelling in this study was the act that PSA levels as a marker of prostate problems including cancer did not increase among any of the male patients. In one case study, with Chein and Terry, growth hormone actually seemed to have reversed the course of the prostate cancer. The patient came to see Dr. Chein with a PSA level of over 50, normal being 0 to 4 and men with cancer usually having a PSA level in the 10s or 20s. The diagnosis of adenocarcinoma was confirmed by a needle biopsy. Although existing cancer is normally a contraindication for hormone replacement therapy, the patient did refuse surgery and urged Dr. Chein to treat him with growth hormone as well as DHEA, melatonin, but not testosterone. In a short period of time the man’s PSA levels came down to between 5 and 7. This is absolutely spectacular as the disease has gone into remission. Dr. Chein speculates that through the immune stimulation of growth hormone, natural killer cells were effectively able to destroy the cancer cells. 

Further clinical studies have similarly failed to link elevated GH and IGF-1 levels with cancer. In fact, arginine, a growth hormone increasing amino acid, has proven anti-tumour effects (chemotherapeutic), and it's use also reduces wasting (cachexia) associated with cancer. 

In each of these cases you can go to the Medline site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
and enter the PMID number to bring up the abstract.

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Orv Hetil 2002 Mar 24;143(12):601-5

[Serum tumor marker levels during a 12-months growth hormone replacement therapy in patients with adult growth hormone deficiency] 

[Article in Hungarian] 

Hubina E, Kovacs L, Szabolcs I, Rimanoczy E, Czirjak S, Goth M. 

Egeszsegtudomanyi Kar, Belgyogyaszati es Geriatriai Klinika, Semmelweis Egyetem, Budapest.

CONCLUSION: The lack of increase of tumor marker levels does not indicate possible oncogenic effect of one-year GH treatment in hypopituitary adults. The authors can not draw any far-reaching conclusions because of the low patient number and the short follow-up, but the measurement of tumor marker levels may provide useful means to follow up long-term therapy and for the early diagnosis of possible occult malignancy. 

PMID: 11963397 [PubMed - indexed for MEDLINE] 

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Eur J Endocrinol 2002 Jul;147(1):59-63

Growth hormone replacement does not increase serum prostate-specific antigen in hypopituitary men over 50 years. 

le Roux CW, Jenkins PJ, Chew SL, Camacho-Hubner C, Grossman AB, Besser GM, Monson JP. 

Department of Endocrinology, St Bartholomew's and the Royal London School of Medicine and Dentistry, St Bartholomew's Hospital, London EC1A 7BE, UK.

RESULTS: Mean serum PSA remained unchanged during rhGH replacement, with a median follow-up of 2 years. No correlation was found between the individual changes in serum IGF-I and changes in serum PSA. CONCLUSIONS: These data are reassuring thus far regarding the safety of GH replacement in relation to the prostate in this patient group. 

PMID: 12088920 [PubMed - indexed for MEDLINE] 

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Clin Endocrinol (Oxf) 2000 Apr;52(4):457-62

One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults. 

Beentjes JA, van Gorkom BA, Sluiter WJ, de Vries EG, Kleibeuker JH, Dullaart RP. 

Department of Internal Medicine, Divisions of; Endocrinology, University Hospital Groningen, The Netherlands. 

CONCLUSIONS: Six to 12 months of GH replacement therapy, aimed to increase plasma IGF-I into the (high) physiological range, does not adversely affect colonic epithelial cell proliferation as a biomarker for the risk of development of colorectal cancer. 

PMID: 10762288 [PubMed - indexed for MEDLINE] 

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Lancet 2002 Jul 27;360(9329):268-9

Comment on: 
Lancet. 2002 Jul 27;360(9329):273-7. 

Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study. 

Swerdlow AJ, Higgins CD, Adlard P, Preece MA. 

Section of Epidemiology, Institute of Cancer Research, Sutton SM2 5NG, UK. a.swerdlow@icr.ac.uk

We have no evidence as to whether growth hormone in modern dosage regimens is associated with an increased risk of colorectal cancer. 

PMID: 12147369 [PubMed - indexed for MEDLINE] 

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