Human Growth Hormone (HGH) and Adult Growth Hormone Deficiency
In childhood, human growth hormone (HGH) controls a child’s height. It is normal for GH levels to decline as a person reaches adulthood, but new research suggests that some adults may have too low a level. Low levels of GH are linked to poor immune system, poor muscle tone, increase body fat, low energy levels, and cardiovascular changes, cholesterol and memory issues. GH insufficiency is associated with pituitary gland problems, brain injury, autoimmune disorders, and nervous system conditions. Growth hormone is not a steroid as many media outlets suggest. Growth Hormone is a delicate sequence of 191 amino acids and works as a “repair” hormone. To take full advantage of HGH, balance and correct your other hormones first.
A better term for growth hormone (GH or hGH) would be healing, repair, or anti-aging hormone. Growth hormone is naturally produced by our pituitary gland and is essential for bone and organ growth in our youth. Although hGH is no longer needed for growth after reaching adulthood, hGH is essential for many other vital functions, and the significantly lowered levels seen as we age are correlated with everything from diminished energy, cardiovascular disease, weight gain (fat), decreased muscle mass, wrinkles, and most other conditions we associate with aging.
Growth hormone diminishes rapidly after the age of 30, and it is this rapid decline that results in many negative aspects of aging, including increased body fat, decreased muscle mass, increased wrinkles, cancer, and heart disease. It is found that growth hormone deficient patients have almost 50% higher rate of death from heart disease than those with more optimal levels. In a 1990 New England Journal of Medicine article, Dr. Rudman reported on his study with the use of human growth hormone in elderly veterans. He discovered that their body fat and wrinkles decreased and lean muscle mass, strength, and bone density increased. The usual progression of aging was halted and reversed by bringing an individual’s growth hormone to a more optimal (youthful) level.
“The effects of six months of human growth hormone on lean body mass and adipose tissue reversed the equivalent of changes incurred during 10-20 years of aging. The overall deterioration of the body that comes with growing old is not inevitable…We now realize that some aspects of it can be prevented or reversed.”
– Dr. Daniel Rudman, MD – New England Journal of Medicine
In 1999, the National Institute on Aging completed another landmark study that was designed to either refute or substantiate the results of Dr. Rudman and also to extend his study by measuring other parameters. This was a double-blind, placebo-controlled, multi-center trial in both men and women with a large number of patients. This study involved not only growth hormone but also the estrogen, progesterone and testosterone. This study not only confirmed the benefits of growth hormone, but also demonstrated that the addition of estrogen/progesterone and testosterone improved the effectiveness of growth hormone.
After 6 months treatment (0.75 I.U./day)
(Percent of patients reporting improvement)
Physical Signs of HGH Treatment
• Less wrinkles on face (75.5%)
• Less sagging skin on face and neck (67%)
• Firmer muscles (60.7%)
• Less body fat (48%)
• Better skin (thicker) (34.5%)
• Thicker head hair (28.1%)>
Emotional/mental Improvements of HGH Therapy
• Improved emotional state (71.4%)
• Increased energy (86.8%)
• Improved physical stamina (86.04%)
• Increased ability to stay up late (82.5%)
• Improved resistance to stress ((83.7%)
• Significantly decreased Anxiety (calmer) (73.5%)
• Improved assertiveness (73.1%)
• Improved sense of power (77.8%)
• Improved self-esteem (50%)
• Depression improved or eliminated (82.7%)
• Improved sociability (77.8%)
• Decreased tendency to give sharp verbal retorts (71.0%)
This study and numerous others demonstrate that treatment with growth hormone results in significant improvements in both physical appearance and in emotional and mental well-being. The enhancement in quality-of-life with the use of Growth Hormone is truly remarkable.
The FDA has approved hGH for adult deficiency after being the most scrutinized pharmaceutical in history. After many years of research and clinical use, growth hormone has proven to have an excellent long and short-term safety profile with almost no side effects.
Growth Hormone and Weight Loss
Effects of growth hormone (hGH) on body composition (weight loss)
In a 1990 study published in the New England Journal of Medicine, the administration of human growth hormone for six months was accompanied by an 8.8 % increase in lean body mass, a 14.4 % decrease in adipose-tissue mass, and a 23.2% improvement in overall body composition. There was a 1.6% increase in average lumbar vertebral bone density, and skin was transformed into a much more youthful appearance with significantly less wrinkles and increased thickness of 7.1 percent.
Change in body composition
Weight of person |
|||
150 pounds |
200 pounds |
250 pounds |
|
Average increase lean muscle Average loss of body fat Overall body composition improvement |
13.2 lbs |
17.6 lbs |
22 lbs
|
Conclusion of the study’s authors: “Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass (fat), and the thinning of the skin that occur in old age. The effects of six months of human growth hormone on lean body mass and adipose tissue reversed the equivalent of 10-20 years of aging.”
In another study published in New England Journal of Medicine, individuals received 6 months of growth hormone plus gonadal steroids (estrogen and progestin for women and testosterone for men). Body composition was analyzed along with strength, lipid profile, and aerobic capacity. There was significant increase in lean muscle mass and a decrease in body fat by 3.5-18%. There was a significant increase in aerobic capacity. There was an improvement in the lipid profile (decrease in total and LDL “bad” cholesterol). There was also a decrease in blood pressure. Overall, there was found to be a significant additive effect of the sex hormones (estrogen / progesterone / testosterone) and hGH resulting in dramatic improvements in body composition and functioning with a reversal of the aging process.
Diagnosis of Growth Hormone Deficiency
LARGE AMOUNTS OF PEER REVIEWED RESEARCH, including long-term data, has demonstrated that growth hormone replacement has been shown to improve energy (1,2), strength (1), cardiac function (3,4,5), blood pressure (6), cholesterol levels (3,6,7,8), insulin sensitivity (6,7,9) cognitive function (10,11), immunity (12,13) and psychological well-being (1,2); decrease body fat (1,3,6,7,9,13,15); increase lean muscle (1,6,14,15); prevent and reverse heart disease (1,3,16,17); prevent and improve osteoporosis (3,7,18); and increase quality of life (2,3,8).
There is an exponential decline in growth hormone release after age 21 with a 50% decline every 7 years. Almost all individuals over 40 years old have a growth hormone deficit and at age 60 growth hormone production is indistinguishable from those of hypopitutitary patients with organic lesions in the pituitary gland. Life with low growth hormone is shown to be poor in quality and quantity (19).
While many endocrinologists feel the diagnosis of growth hormone deficiency requires the use of growth hormone stimulation testing (dynamic testing), growth hormone and other stimulation tests are shown to be inaccurate, highly variable, nonphysiologic, lack adequate sensitivity to detect relative growth hormone deficiencies, do not correlate with the presence of deficiency and do not predict who will respond to therapy (20-32). Requiring stimulation testing to confirm growth hormone deficiency is unnecessary, expensive and carries significant risk to the patient. Thus, they neither are appropriate to perform nor required for the diagnosis of growth hormone deficiency. A clinical diagnosis of growth hormone deficiency, often with support of low or low-normal IGF-1 levels, are the most appropriate means of making the diagnosis of relative growth hormone deficiency.
Hoeck et al evaluated the accuracy of the insulin tolerance test (ITT), which is considered to be the most reliable (and risky) of the dynamic tests. They found that there was no correlation between results of repeated ITT’s, and the results were no better than flipping a coin. The authors conclude, “The results of this study illustrate the complexity of the regulation of growth hormone secretion and indicate that the ITT is less useful for diagnosing growth hormone deficiency in adults than previously anticipated. The diagnosis of growth hormone deficiency in adults and especially in adult females should not be based on the results of a single ITT alone (24).”
Similarly, Hoeck and Jakobsen, et al evaluated the accuracy and reliability of commonly used stimulation tests. On each subject, 2 ITT, 2 GHRH, 2 clonidine + GHRH were done and then a pyridostigmine + GHRH stimulation tests were done on an extended group of subjects. It was found that there was no correlation in the results of the different tests and the results were not reproducible. The authors conclude, “In the individual subject, there was no systematic correlation between the peak growth hormone responses in the different stimulation tests. In conclusion, we found that the stimulated growth hormone responses were highly variable in all tests, and that the peak GH responses differed (25).” The authors expressed caution in the use and interpretation of stimulation tests in the diagnosis of growth hormone deficiency.
This use of growth hormone stimulation testing in the diagnosis of growth hormone deficiency was reviewed by Rosenfeld et al in the Journal of Endocrinology and Metabolism. The authors state, “[stimulation testing] is often limited and relies on testing procedures that are, generally, nonphysiolgical, arbitrary, invasive, risky, and subject to considerable interassay variability (20).”
Moorkens et al evaluated the growth hormone secretion in chronic fatigue syndrome patients as compared to normal controls. This study compared physiologic nocturnal secretion, IGF-1 levels and response to various commonly used stimulation tests. This study found that CFS patients have an abnormally low production of growth hormone, as demonstrated by reduced nocturnal secretion of growth hormone and a significantly decreased GH response to ITT (both peak and AUC). The commonly used stimulation tests were shown, however, to have no correlation with ITT testing results (which again has significant risk), and that these stimulation tests were shown to lack the sensitivity to detect significant growth hormone deficiency in these patients (32).
In a prospective randomized placebo controlled study, Rahim et al assessed the accuracy and reliability of commonly used stimulation tests by performing four different stimulation tests on each individual (ITT, glucagon, arginine and clonidine). As with other studies, this study also found that there was no correlation between the response to different agents in the same individual. Subjects who failed to achieve a growth hormone peak greater than 20mU/l in one test were not the same individuals who responded poorly to other tests. Again, the results of the stimulation tests were no better than flipping a coin. This study also demonstrated the risk and side-effects of performing such testing; all patients suffered from significant hypotension; over half of the patients could not carry out normal daily activities for the rest of the day after the tests; venous thrombosis occurred in over a third of patients and over 10% had significant nausea and vomiting (26). There have also been reported deaths and neurological damage associated with growth hormone stimulation testing (33).
Cacciari et al investigated the sensitivity of utilizing growth hormone stimulation tests in 98 children with clear evidence of impaired growth hormone production compared to 274 healthy controls. They found that growth hormone deficiency correlated with IGF-1 levels, but that standard arbitrary cutoffs of what is considered to be a normal IGF-1 level and the use of growth hormone stimulation tests with standard cutoffs lacked sufficient sensitivity. The majority of patients with clear evidence for growth hormone deficiency would have been inappropriately labeled as normal and children who would likely have benefited from treatment would have been left untreated. The authors conclude, “Our data adds weight to the opinion that present criteria for defining growth hormone deficit may be too restrictive. Consequent implications regarding therapy are evident (27)”
Wilson et al reviewed the use of growth hormone stimulation tests in determining a person’s growth hormone secretory status in a 2005 edition of Growth Hormone & IGF Research. They state, “Historically, growth hormone stimulation testing has played a prominent role in diagnosing growth hormone deficiency. There are growing concerns, however, that growth hormone stimulation testing, particularly as currently conducted in the USA, is neither precise nor accurate in quantifying a patients growth hormone secretory status (28).”
Tassoni et al tested the variability of growth hormone stimulation tests in the Journal of Endocrinology and Metabolism. They performed several commonly used stimulation tests in duplicate as well as 12-hour overnight physiologic growth hormone secretion testing. They found that there was little or no correlation between repeated testing in the same individuals (coefficient of variance being 89% in one group and 66% in another) as well as little correlation with physiologic night-time growth hormone secretion. When the same stimulation test was repeated on the same individual, over half had disparate results (showing deficient on one test and normal on the other). Again, the results were almost no better than flipping a coin. They state that growth hormone stimulation tests cannot be used with any confidence to diagnose or rule-out growth hormone deficiency and recommend that repeated 12-hour overnight physiologic growth hormone secretion testing be utilized. This requires, however, that multiple venous samples be obtained throughout the night via an indwelling catheter, which is not practical outside of a research setting. The authors state, “In conclusion, the usual approach for evaluating growth hormone secretion does not take into account the variability of the response to the various tests. This may be misleading, especially for patients that have hormone secretion at the lower limit of normalcy (30).”
Gandrud et al reviewed the use of growth hormone stimulation testing in the 2004 Growth Hormone & IGF Research. This extensive review clearly demonstrates that growth hormone stimulation tests lack precision and accuracy, are not concordant with the proper diagnosis of growth hormone deficiency and do not predict response to therapy. They recommend that the diagnosis of growth hormone deficiency should be based on clinical parameters as well as IGF-1 and state, “…the insulin tolerance test using the current cutoff for failure should not be considered the gold standard for the diagnosis of growth hormone deficiency…We examined the pitfalls associated with growth hormone stimulation tests, specifically, the lack of reliability and accuracy of these tests, and their inability to predict who will benefit from growth hormone therapy. We recommend that growth hormone stimulation tests no longer routinely be used for the diagnosis of growth hormone deficiency…(31).”
Conclusion: Aging adults are shown to have a relative deficiency of growth hormone and supplementation with growth hormone can be of significant benefit. A clinical diagnosis of growth hormone deficiency, often with support of low-normal IGF-1 levels, are the most appropriate means of making the diagnosis of growth hormone deficiency. Growth hormone stimulation tests are shown to be inaccurate, unreliable, highly variable, risky, nonphysiologic and lack adequate sensitivity to detect relative growth hormone deficiencies. Thus, the growth hormone stimulation tests generally do not add significant useful information in the clinical management of these patients and are not recommended.
References
1. Gibney J, Wallace JD, Spinks T, Schnorr L, Ranicar A, et al. The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Met 1999;84(8):2596-602.
2. 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;104(3):227-31.
3. Johannsson G, Svensson J, Bengtsson BA. Growth hormone and ageing Growth Hormone and IGF Research 2000;10(2):25-30.
4. Maison P, Philippe C. Cardiac Effects of Growth Hormone in Adults With Growth Hormone Deficiency: A Meta-Analysis. Circulation. 2003;108:2648.
5. Cho GY, Jeong IK, Kim SH, Kim MK, Park WJ, Oh DJ, Yoo HJ. Effect of growth hormone on cardiac contractility in patients with adult onset growth hormone deficiency. Am J of cardiology 2007;100(6):1035-9
6. Johannsson G et al. GH treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism and reduces diastolic BP. J Clin Endocinol Metab 1997;82:727-734.
7. Gotherstrom G et al. A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices. J Clin Endocrinol Metab 2001;86(10):4657-65.
8. Feldt-Rasmussen B, Lange M, Sulowicz W, Gafter U, et al. Growth hormone treatment during hemodialysis in a randomized trial improves nutrition, quality of life, and cardiovascular risk. J Am Soc Nephrology 2007;18(7):2161-71.
9. Yuen KC , et al. Impact of treatment with recombinant human GH and IGF-I on visceral adipose tissue and glucose homeostasis in adults. Growth Horm IGF Res 2006;16:S55-61.
10. 7A. Aleman A et al. Insulin-Like Growth Factor-I and Cognitive Func¬tion in Healthy Older Men J Clin Endocrinol Metab 84:471–475, 1999.
11. Arwert LI, Veltman DJ, Deijen JB, Sytze van Dam P, Drent ML. Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study. Neuroendocrinology 2006;83:12–19.
12. Clark R. The somatogenic hormones and insulin-like growth factor-1: stimulators of lymphopoiesis and immune function. Endocr Rev 1997;18(2):157-7.
13. Burgess W et al. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I. Neuroimmuno¬modulation 1999;6(1-2):56-68.
14. Rudman D. Effects of growth hormone in men over 60 years old. New England Journal of Medicine 1990;323(1):1-6.
15. Munzer T, Harman SM, Hees P, Shapiro E, Christmas C, et al. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 2001;86(8):3604-10.
16. Pfeifer M et al. growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults J Clin Endocrinol Metab 1999;84: 453–457.
17. Borson-Chazot F, Serusclat A, Kalfallah Y, Ducottet X, Sassolas G, et al. Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab 1999;84:1329–1333.
18. Valimaki MJ et al Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 1999;140(6):545-54.
19. Savine R, Sonksen P. Growth Hormone-Hormone replacement for the somatopause. Horm Res 2000;53(3):37-41.
20. Rosenfeld et al. Diagnostic Controversy: The diagnosis of childhood growth Hormone deficiency revisited. Journal of Endocrinology and Metabolism 1995;80(5):1532-40.
21. Cacciari E, Cicognani A, Pirazzoli P, Tassoni P, Salardi S, Capelli M, Zucchini S, Natali G, Righetti F, Ballardini D.Differences in somatomedin-C between short-normal subjects and those of normal height. J Pediatr. 1985 Jun;106(6):891-4.
22. Bennett R. Growth Hormone in Musculoskeletal Pain States. Current Pain and Headache Reports 2005, 9:331-338
23. Maghnie M et al. Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement. European Journal of Endocrinology 2005;152(4):589-96.
24. Hoeck HC, Vestergaard P, Jakobsen PE, Laurberg P. Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endo 1995;133:305-12.
25. Hoeck HC, Jakobsen PR, Vestergaard P, Falhof JF, Laurberg P. Differences in reproducibility and peak growth hormne responses to repeated testing with various stimulators I health adults. Growth Hormone & IGF Research 1999;9:18-24.
26. Rahim A, Toogood AA, Shalet SM. The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endo 1996;45:557-62.
27. Cacciari E, Cicognani A, Pirazzoli P, Tassoni P, Salardi S, et al. Differences in somatomedin-C between short-normal subjects and those of nomal height. J Pediatrics 1985;106:891-4.
28. Wilson DM, Frane J. A brief review of the use and utility of growth hormone stimulation testing in the NCGS: Do we need to do provocative GH testing? Growth Hormone & IGF-1 Research 2005;15:S21-5. 29. Bennett RM, Clark SR, Campbell SM, Burckhardt CS. Low levels of Smoatomedin C in patients with fibromyalgia syndrome. Arthritis & Rheumatism 1992; 35(10):1113-6.
30. Tassoni P, Cacciari E, Cau M, Colli C, et al. Variability of growth hormone response to pharmacological and sleep tests performed twice in short children. J Endo Met 1990;71(1):230-4.
31. Gandrud LM, Wilson DM. Is growth hormone stimulation testing in children still appropriate? Growth Hormone & IGF-1 Research 2004;14:185-94.
32. Moorkens G, Berwaerts J, Wynants H, Abs R. Characterization of pituitary function with emphasis on GH secretion in chronic fatigue syndrome. Clin Endo 2000;53:99-106.
33. Shah A, Stanhope R, Matthew D. Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ 1992;304:173-4.
Scientific Review of Growth Hormone
Kent Holtorf, M.D.
Section 1: Growth hormone (hGH) results in decreased body fat, increased lean muscle, decreased heart disease and an increase in quality of life.
1. “The overall deterioration of the body that comes with growing old is not inevitable…We now realize that some aspects of it can be prevented or reversed.” Effects of 10-20 years of aging on lean body mass and adipose tissue reversed in 6 months with testosterone and hGH.
Daniel Rudman, M.D. Effects of Growth Hormone in Men over 60 Years Old, New England Journal of Medicine. 1990 Jul 5;323(1):1-6.
2. Life with low growth hormone (GH) is poor both in quantity and quality
– GH peaks at puberty and begins to decrease at 21.
“At age 60 most adults have total 24-hour secretion rates indistinguishable from those of hypopituitary patients with organic lesions in the pituitary gland. Almost all adults 40 years of age or older have a growth hormone (IGF-1) deficit.”
Savine R. Growth hormone replacement for the somatopause. Horm Res 2000;53 Suppl 3:37-41Savine R. et al.
3. Growth hormone decreased body fat in men and women by 14% and increased lean muscle in both men and women.
– Synergistic with testosterone (decreased body fat 17-18%)
– GH resulted in substantial increase in aerobic capacity, a decrease in total and LDL (bad) cholesterol, improved cholesterol coronary risk ratio, and hGH lowered PSA.
Mark Blackman of Johns Hopkins University and National Institute on Aging
4. “The fall in GH secretion seen with ageing coincides with changes in body composition and lipid metabolism that are similar to those seen in adults with GH deficiency.”
Growth hormone has a positive effect on lean body mass, central fat, low-density lipoprotein cholesterol and aerobic capacity.
Savine R. Is the Somatopause an indication for growth hormone replacement?
J Endocrinol Invest 1999;22(5 Suppl):142-9
5. Low IGF-1 (measurement of low growth hormone) in older women results in poor muscle strength, slow walking speed, and difficulty with mobility tasks.
J Clin Endocrinol Metab 2001 Sep;86(9):4139-46
Cappola AR et al. Association of IGF-I levels with muscle strength and mobility in older women.
6. Aging and adult growth hormone deficiency both have:
– Increased Cardiovascular morbidity and mortality
– Decreased muscle mass and bone mass
– Increased total and visceral fat
– Increased LDL (bad cholesterol)
With hGH supplementation
– Body composition changes – reduction in total and visceral fat and increase in lean body mass
– Improvement in cardiovascular function and lipids
– Reverse atherosclerotic changes in carotids
– Quality of life improves
– Bone mineral density increases
Johannsson et al. Growth Hormone and IGF Research 2000, Supplement B 25-30
7. HGH deficiency results in abnormal body fat and distribution and insulin resistance. HGH replacement results in increased lean body mass, decreased abdominal fat by up to 50%, and increased insulin sensitivity (prevents diabetes).
Christiansen, J. Effects of GH upon body composition.. Growth Hormone in Adults , 1996, Cambridge University Press
8. HGH secretion impaired in obesity
– GH decreases adiposity
– Inhibits lipoprotein lipase
– Enhances lipolysis
– Improves dyslipidemia
Nam SY et al. Growth Hormone and Adipocyte Function in Obesity.
Horm Res 2000 Jul;53 Suppl S1:87-97
9. Middle age men with low GH and abdominal obesity
– 9 months of GH treatment (9.5 microg/kg/day)
– Decreased abdominal visceral fat by 18% and subcutaneous fat by 6%
– Improved insulin sensitivity (prevents diabetes)
– Total Cholesterol, LDL, and triglycerides decreased
– Diastolic BP decreased
Johannsson G et al. GH treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism and reduces diastolic BP. J Clin Endocinol Metab 1997;82:727-734.
10. 5 years hGH Replacement
– Significant Increases in:
– Lean body mass
– Bone mineral density
– HDL-C (good cholesterol)
-Significant decrease in:
– Total Cholesterol
– LDL-C (bad cholesterol)
– Triglycerides
– Hemoglobin A1C (lower glucose levels and prevents diabetes)
“5 year GH substitution is safe and well tolerated”
Gotherstrom G et al. A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices. J Clin Endocrinol Metab 2001 Oct;86(10):4657-65
11. GH +/- Sex steroids and subcutaneous and visceral fat with a combination of growth hormone, HRT and testosterone.
Munzer T, Harman SM, Hees P, Shapiro E, Christmas C, Bellantoni MF, Stevens TE, O’Connor KG, Pabst KM, St Clair C, Sorkin JD, Blackman MR. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 2001 Aug;86(8):3604-10
12. HGH deficiency results in impaired physical performance, and hGH replacement increases exercise capacity
Johansson, J. Psychosocial and CNS effects.. Growth Hormone in Adults
1996, Cambridge University Press
Juul, A. Adult GH deficiency and effects of GH treatment on muscle strength, cardiac function and exercise performance. GH in adults, Cambridge University Press, 1996, p 254-241
13. HGH Deficiency results in chronic fatigue and depression, and hGH Replacement results in:
– Increased sense of well-being
– Improved quality of life
Gibney et al. The effects of 10 years of GH in adult GH deficient patients
J Endocrin Metab 1999 August
Section 2: Growth Hormone and the Brain
1. Adult nerve cells are targets of IGF-1
– IGF-1 increases dendritic formation of cortical neurons (improved mental function)
Riddle D. Role of IGF -1 in cortical dendritic growth Journal of GH and IGF Research Oct 99
Caro, E et al Body to brain signaling mediated by circulating IFG-1. Journal of GH and IGF Research Oct 99
2. IGF-1 reverses age-related D2 (Dopamine) receptor deficits and improve age related impairment in learning and memory
Thornton et al. Journal of GH and IGF Research Oct 99.
3. IGF-1 correlated with cognitive function in men average age 69
– GH deficiency correlated with poor emotional and psychosocial functioning
Aleman A et al. Insulin-Like Growth Factor-I and Cognitive Function in Healthy Older Men J Clin Endocrinol Metab 84:471–475, 1999
4. GH increases connexin-43 (improved mental function)
– In cerebral cortex
– In hypothalamus
– IGF-1 does not increase connexin-43
– Connexin-43 forms gap junctions that mediate intercellular communication and improved mental function
– Increased neuronal communication
Aberg ND. Growth hormone increases connexin-43 expression in the cerebral cortex and hypothalamus. Endocrinology 2000 Oct;141(10):3879-86
5. HGH exerts profound effects on CNS and improves:
– Cognitive capabilities
– Memory
– Alertness
– Motivation, Work Capacity
– GH receptors present in the brain
– Hypothalamus, choroid plexus, hippocampus
– GH crosses BBB
Nyberg F. Growth Hormone in the Brain: Characteristics of Specific Brain Targets for the Hormone and Their Functional Significance.
Front Neuroendocrinol 2000 Oct;21(4):330-348.
6. IGF-I exerts cytoprotection against A beta-amyloid induced neuronal cell death (prevents Alzheimer’s disease)
Takako Niikura et al. Insulin-Like Growth Factor I (IGF-I) Protects Cells from Apoptosis by Alzheimer’s V642I Mutant Amyloid Precursor Protein through IGF-I Receptor in an IGF-Binding Protein-Sensitive Manner The Journal of Neuroscience, March 15, 2001, 21(6):1902-1910
Section 3: Growth Hormone and Bone
1. GH Deficiency causes reduced bone density
– GH Replacement reverses osteoporosis
Logobardi, J Endocinol Invest, May 1999
2. Bone density significantly improved with hGH therapy
– Increases formation and strength of cortical bone.
– Synergistic effect with exercise
– Lower growth hormone levels are found in patients with bone fractures
Growth Hormone and Mild Exercise in Combination Markedly Enhance Cortical Bone Formation and Strength in Old Rats H. Oxlund, et al Endocrinology, April 1998, p. 1899-1904 Vol. 139, No 4
Colao A.Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999 Jun;84(6):1919-24
Hedstrom M. Hip fracture patients, a group of frail elderly people with low bone mineral density, muscle mass and IGF-I levels. Acta Physiol Scand 1999 Dec;167(4):347-50.
3. Effect of hGH on body composition and bone turnover in women with osteoporosis
– Increase in handgrip strength
– Decrease in waist/hip ratio
– Increased bone formation
– Decreased osteoporosis
Sugimoto T et al. Effect of recombinant human growth hormone in elderly osteoporotic women. Clin Endocrinol (Oxf) 1999 Dec;51(6):715-724
4. Growth hormone replacement in men (18 month study)
– Increase bone density and lean body mass
– Body fat decreased
– Low incidence of side effects
5. 42 month study
– Increases of bone mineral density in spine and femoral neck
– Patients with osteopenia (low bone mass) were reduced by 50%
– Better results in males and younger
“GH deficient patients with osteoporosis or osteopenia should be considered candidates for GH replacement”
Valimaki MJ et alEffects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 1999 Jun;140(6):545-54
Section 4: Growth Hormone and the Heart
1. GH Deficiency associated with
– Increased Cardiovascular (CV) Deaths
– GH Replacement results in:
– Increased CV function
– Improves lipid profile
– Reverses arteriosclerosis
– Reduced carotid intima thickness
– Improves dilated cardiomyopathy
Gibney et al. The effects of 10 years of GH in adult GH deficient patients
J Endocrin Metab 1999 August
2. GH and Atherosclerosis
– GH normalized Intima Media thickness (IMT) of carotid artery in 3 months and improvement continued 18 months of study
– IMT negatively correlated with IGF-1
– No significant change in lipids
– Direct effect on arterial wall via Nitric oxide
Pfeifer M et al. Growth Hormone (GH) Treatment Reverses Early atherosclerotic Changes in GH-Deficient Adults J Clin Endocrinol Metab 84: 453–457, 1999.
Borson-Chazot F. et al. Decrease in Carotid Intima-Media Thickness after One Year Growth Hormone (GH) Treatment in Adults with GH Deficiency J Clin Endocrinol Metab 84: 1329–1333, 1999.
3. Growth hormone improves cardiac performance
– Increases contractility and cardiac output
– Improves cardiac function in dilated cardiomyopathy
Fazio et al. A preliminary study of GH in the treatment of dilated cardiomyopathy. NEJM 1996:334:809-814
Isgaard J et al. GH improves cardiac function in rats with experimental MI. Eur J Clin Invest 1997;27:517-525
Tivesten, AThe Growth Hormone Secretagogue Hexarelin Improves Cardiac Function in Rats after Experimental Myocardial Infarction. Endocrinology, January 2000, p. 60-66 Vol. 141, No. 1
4. Growth hormone treatment in heart failure patient increased
– Ejection fraction 13% to 28% (doubled heart function)
– Heart medications able to be discontinued
Bocchi EA et al. Growth hormone for optimization of refractory heart failure treatment. Arq Bras Cardiol 1999 Oct;73(4):391-8
5. Cardiac Performance Impaired in GH deficiency
– Reduction of LV mass
– Reduction of ejection fraction
– Reversed after GH replacement
Colao A et al. Impaired cardiac performance in elderly patients with growth hormone deficiency J Clin Endocrinol Metab 1999 Nov;84(11):3950-5
6. GH decreases coronary inflammation and prevents heart attacks
– GH deficient adults have increased cardiovascular mortality
– Inflammatory markers are predictive of cardiovascular events
– C-Reactive Protein increased in GH deficiency
– With GH Replacement therapy:
– C Reactive protein decreased
– Visceral and Subcutaneous fat decreased
– Lipoprotein(a) decreased
– No change in cholesterol, HDL
Sesmilo G et al.
Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial. Ann Intern Med 2000 Jul 18;133(2):111-22
7. IGF-1 and the heart
– Improves cardiac contractility, cardiac output, stroke volume, ejection fraction.
– Improves cardiac function after myocardial infarction by stimulating contractility and promoting tissue remodeling.
– Facilitates glucose metabolism, lowers insulin levels, increases insulin sensitivity, and improves the lipid profile
Ren J et al. Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol 1999 Nov;31(11):2049-61
8. HGH Increases coronary blood flow and capillary density
– Decline in GH leads to decline in tissue growth, maintenance and repair in older animals (and humans)
– Deterioration of cardiovascular function contributes to decline of physical function and quality of life
– Decreased coronary flow and capillary density with aging reversed by GH
Khan AS et al. Growth hormone increases regional coronary blood flow and capillary density in aged rats. J Gerontol A Biol Sci Med Sci 2001 Aug;56(8):B364-71
Section 5: Growth Hormone and Immune System
1. Connection between neuroendocrine and immune and GH/IGF-1
– IGF-1 needed for lymphocyte maturation and function
– IGF-1 restores age-related thymic involution in rodents
– IGF-1 restores damaged immune system
– Decline in T and B cells are restored by GH
Clark R. The somatogenic hormones and insulin-like growth factor-1: stimulators of lymphopoiesis and immune function. Endocr Rev. 1997 Apr;18(2):157-7
Burgess W et al. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I. Neuroimmunomodulation 1999 Jan-Apr;6(1-2):56-68.
Section 6: Growth Hormone and Crohn’s Disease
1. Significant improvement in patients treated with hGH
Slonim AE et al. A preliminary study of growth hormone therapy for Crohn’s disease. N Engl J Med 2000 Jun 1;342(22):1633-7
Section 7: GH and Chronic Fatigue and Fibromyalgia (See CFIDS and Fibromyalgia page)
1. GH deficiency mimics Fibromyalgia
– Low GH secretion, IGF-1 and IGFBP3 in Fibromyalgia
– Rx with HGH or GHRH produced increases in IFG-1 and IGFBP3
– Can be significant improvement with GH replacement
LEAL-CERRO A. et al. The Growth Hormone (GH)-Releasing Hormone – GH -Insulin-like Growth Factor-1 Axis in Patients with Fibromyalgia Syndrome J Clin Endocrinol Metab 84: 3378–3381, 1999
2. Growth Hormone deficiency more common in Fibromyalgia patients
– Supplementation with hGH can result in improvement in symptoms
Bennett RM, Z Rheumatol 1998;57 Suppl 2:72-6
3. Growth hormone supplementation results in significant improvement in symptoms
“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.”
Bennett RM; Clark SC; Walczyk JAm J Med 1998 Mar;104(3):227-31
USA Today
November 15, 2000 Issue
“Boomers Believe They’ve Found a Fountain of Youth In a Syringe”
Edited Abstract of Article
High-profile Hollywood celebrities boast that using hormone modulation, including human growth hormone (hGH), has them looking better and feeling better. Praising hormone modulation as a way to stay healthy as long as one can, enthusiasm is growing for an anti-aging revolution, with hGH and vitamins as its focus.
HGH is produced by the body in the pituitary gland, and, as we age, the body’s natural hGH levels begin to drop (around the age of 30 or so). Advocates claim that supplementing the waning levels of our own hGH with injections of bioengineered human growth hormone restores the body’s ability to grow muscle tissue, increases bone density, restores energy, enhances memory, and instills a sense of well-being. In other words, it brings one back to the level of age 30 or so.
The specialty of anti-aging medicine began with research about 15 years ago; the Food and Drug Administration approved hGH for “deficient” adults in 1996; and Harvard University proctored the first medical board examinations for anti-aging practitioners in 1997. While there is still some controversy as to whether the symptoms of aging are sufficient to categorize a person as growth hormone deficient, the use of hGH as part of an anti-aging protocol is the edge of a futuristic field of medicine that promises biomedical breakthroughs in many life-preserving areas: regeneration, gene mapping, etc.
Generally, an anti-aging program begins with a comprehensive evaluation of nutritional, metabolic, immune and hormonal functions. The preliminary diagnostics can reveal deficiencies in a number of areas—early signs of osteoporosis, thyroid conditions, blood-sugar imbalances, etc, and regimens are then prescribed to correct these deficiencies. Depending upon the patient’s particular medical needs, the program may include hGH.
Despite internet or advertising scams offering inexpensive sprays or pill forms of hGH, the hormone is potent only when injected. In combination with other anti-aging medical protocols, it has been shown to lower blood pressure, build lean muscle, decrease body fat, improve skin tone, heighten sexual potency, and ensure restful sleep. Some advocates have said that it also thickens hair and sharpens vision, but these are anecdotal accounts. Skeptics point out that the potential side-effects include joint discomfort, carpal tunnel syndrome, fluid retention, and insulin resistance. These problems, however, are generally from larger doses and corrected by simply adjusting the patient’s dosage. Other critics are concerned about “putting things into our body that aren’t naturally there.” Dr. Ronald Klatz, head of the American Academy of Anti-Aging Medicine (A4M), gets exasperated with such nay-sayers. “This is something that we have studied” and “has been in clinical use for the last 50 years. There are tens of thousands, if not hundreds of thousands, of people who have received growth hormone—whether they be children or adults.”
Patients, such as Gilman, say, “Every single thing it [hGH] promised, it has delivered with absolutely zero side effects.” Dan Yaffe, 52, a mortgage banker in Las Vegas and hGH user is another believer, even with the high cost. “As long as I’m living,” says Yaffe, I want to be as healthy and physically fit as possible. What better thing could I put my money into?”
As 20 million baby-boomers turn 50 and another 22 million turn 40, more and more products and programs will be offered through anti-aging practitioners. It is important to remember that hGH is not effective unless it is injected. You need a doctor’s prescription and should be under the supervision of a qualified practitioner to monitor your hormone levels.