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HGH REFERENCES
The following references to clinical studies published in the peer reviewed medical literature provide evidence that HGH can significantly lower risks of many diseases with relative safety, and can also greatly improve the quality of life by relieving many adverse symptoms associated with aging—often when IGF-1 measurements fall within age-adjusted laboratory reference ranges on report forms. (Occasional duplications occur where references apply to multiple disease or symptom categories)
A. Impaired brain function correlates with lower IGF-1 levels
Aroonsakul, C. "Reduced Growth Hormone in Alzheimer's Disease," Journal of Advancement in Medicine, 1995; 8 (3): 206-208. Higher risk of Alzheimer's at lower lGF-1 levels.
Kyle UG, Jolliet P, Genton L, Meier CA, Mensi N, Graf JD, Chevrolet JC, Pichard C. Clinical evaluation of hormonal stress state in medical lCU patients: a prospective blinded observational study. Intensive Care Med. 2005 Dec;31 (12):
1669-75. Department of Nutrition, Geneva University Hospital, 1211, Geneva, Switzerland. Higher risk of higher stress related problems at lower lGF-1 levels in intensive care unit patients
Watanabe T, Miyazaki A, Katagiri T, Yamamoto H, Idei T, Iguchi T. Relationship between serum insulin-like growth factor-1 levels and Alzheimer's disease and vascular dementia. J Am Geriatr Soc. 2005 Oct;53(10):1748-53. Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
[email protected] Higher risk of memory loss (lower score in the Mini-Mental State Examination) at low lGF-1 levels in elderly subjects
Kalmijn S, Janssen JA, Pols HA, Lamberts SW, Breteler MM. A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. J Clin Endocrinol Metab. 2000 Dec;85(12):4551-5. Departments of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, 3000 DR Rotterdam, The Netherlands. Higher risk of mental decline relative to IGF-1 levels in healthy persons, aged 55-80 yr
Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, Grunfeld C. Ann Intern Med. Growth hormone replacement in healthy older men improves body composition but not functional ability.1996 Apr 15;124(8):708-16. University of California, San Francisco, California, USA. HGH treated patients gained 12 percent in mental dexterity test
Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. 2006 Feb;27(2):318-23. Epub 2005 Mar 23. Department of Psychiatry and Behavioral Sciences, BB-1520D Health Science Building, University of Washington. Increasing levels of HGH partially ameliorated cognitive declines in otherwise healthy older adults and potentially in individuals with impaired cognitive function (i.e., mild cognitive impairment and Alzheimer's disease). GHRH resulted in higher HGH release, improved performance on WAIS-R performance IQ (p<0.01), WAIS-R picture arrangement (p<0.01), finding A's (p<0.01), verbal sets (p<0.01) and single-dual task (p<0.04). GHRH-based improvements were independent of gender, estrogen status or baseline cognitive capacity.
Abbasi AA, Drinka PJ, Mattson DE, Rudman D. Low circulating levels of insulin-like growth factors and testosterone in chronically institutionalized elderly men. J Am Geriatr Soc. 1993 Sep;41 (9):975-82. Department of Medicine, Medical College of Wisconsin, Milwaukee. Higher risk of dementia at younger age inversely associated with lGF-1 levels in institutionalized older men
Wilson K, Broadhurst C, Diver M, Jackson M, Mottram P. Plasma insulin growth factor-1 and incident delirium in older people. Int J Geriatr Psychiatry. 2005 Feb;20(2):154-9. Elderly Mental Health Academic Unit, University of Liverpool, Liverpool, UK. Risk of delirium is relatied to lower lGF-1 in patients aged 75 and over
B. Cardiovascular diseases associated with lower IGF-1 within Normally Reported Age-Adjusted Reference Ranges
Fernando Cordido,Jesuus Garcia-Buela, Susana Sangiao-Alvarellos, Teresa Martinez, Ovidio Vidal. The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors. Mediators of Inflammation. Volume 2010, Hindawi Publishing Corporation, Article ID 434562, GH secretion was inversely associated with fasting insulin (R = −0.650, P = .012), HOMA-IR (R = −0.846, P = .001), total cholesterol (R = −0.532, P = .034), and LDL cholesterol (R = −0.692, P = .006) and positively associated with HDL cholesterol (R = 0.561, P = .037).
Janssen JA, Stolk RP, Pols HA, Grobbee DE, Lamberts SW. Serum totaIIGF-I, free IGF-I, and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease. ArteriosclerThrornb Vasc Biol. 1998 Feb;18(2):277- 82. Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
Blood levels of triglycerides are inversely related to lGF-1 levels in healthy persons aged 55 to 80 years
van den Beld AW, Bots ML, Janssen JA, Pols HA, Lamberts SW, Grobbee DE. Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol. 2003 Jan 1; 157(1 ):25- 31. Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. Premature atherosclerosis associated with lower lGF-1 levels in elderly men
Leonsson M, Hulthe J, Johannsson G, Wiklund 0, Wikstrand J, Bengtsson BA, Oscarsson J. Increased Interleukin-6 levels in pituitary-deficient patients are independently related to their carotid intima-media thickness. Clin Endocrinol (Oxf). 2003 Aug;59(2):242-50. Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Gtiteborg, Sweden. Risk of premature atherosclerosis found associated with lower lGF-1 levels in men and women
Cittadini, A., et al. "Impaired cardiac performance in hGH-deficient adults and its improvement after hGH replacement," American Journal of Physiology, 1994; 267 (Endocrinol. Metab. 30): E219-E225.
Fazio, S., Sabatini, D., Capaldo, B., Vigorito, C., Giordano, A., Guida, R., et al. (1996). A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. The New England Journal of Medicine, 334(13), 809-814. Retrieved September 27, 2006. Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.
Volterrani M, Giustina A, Manelli F, Cicoira MA, Lorusso R, Giordano A.Role of growth hormone in chronic heart failure: therapeutic implications. Ital Heart J. 2000 Nov;1(11):732-8. Division of Cardiology, Salvatore Maugeri Foundation, Medical Center, Gussago, Italy. In small open studies, acute and chronic GH treatment has demonstrated beneficial effects in patients with heart failure due to ischemic or idiopathic cardiomyopathy.
Pfeifer M, Verhovec R, Zizek B. Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment. Growth Horm IGF Res 1999 Apr;9 Suppl A:25-30. Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia. 12 HGH deficient men were compared with 12 healthy men for 2 years. The higher the HGH levels, the less the atherosclerosis, measured by increases in carotid artery wall thickness (plaque formation). HGH replacement therapy by injection was then found to reverse atherosclerotic changes in major arteries of GH deficient men.
Efstratiadis G, Tsiaousis G, Athyros VG, Karagianni 0, Pavlitou-Tsiontsi A, Giannakou-Darda A, Manes C. Total serum insulin-like growth factor-1 and C-reactive protein in metabolic syndrome with or without diabetes. Angiology. 2006 May-Jun;57(3):303-11. Department of Nephrology, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. Higher risk of increased CRP, an inflammation and atherosclerosis marker, is related to lower IGF-1 levels in men and women
Gibney J, Wallace JD, Spinks T, Schnorr L, Ranicar A, Cuneo RC, Lockhart S, Burnand KG, Salomon F, Sonksen PH, Russell-Jones D. The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Metab 1999 Aug;84(8):2596-602. Department of Medicine, St. Thomas Hospital, London, United Kingdom. Twenty-one GH-deficient adults were separated into two groups. Ten received HGH for 10 years, 11 did not. They were matched for age and sex and re-evaluated periodically. LDL lipoprotein decreased in HGH group improving risk for atherosclerosis and cardiovascular disease. Lean body mass was higher and fat was considerably less in the treated group. Carotid artery atherosclerosis was less in treated group. Energy levels and emotional and psychological well being were significantly better in the treated group.
Tacke J, Bolder U, Herrmann A, Berger G, Jauch KW. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone. JPEN J Parenter Enteral Nutr. 2000 May-Jun;24(3):140-4. Department of Surgery, Dortmund Academic Hospital, Germany. Recombinant human growth hormone (rhGH) promotes protein synthesis, accelerates wound healing, and maintains immune function in the catabolic state. The results demonstrate no evidence for an increased risk of tumor recurrence after rhGH treatment after removal of a gastrointestinal adenocarcinoma. Therefore, the positive metabolic effects of rhGH application can be used safely in the treatment of the postoperative catabolic state in the patient groups investigated.
Tucker ME. Growth hormone therapy appears safe in long term, 11-1-2004; Family Practice News; Volume 34, Number 21. Report from the podium by Mark L. Hartman, M.D., who presented this study report at the 12th International Congress of Endocrinology: A group of 2,429 elderly patients was followed for 2.3 years. Baseline IGF-1 levels were within normally reported reference ranges. 1,988 patients were treated with injectable human growth hormone (rHGH) replacement. They were compared to 441 similar patients who did not receive HGH. Bias was eliminated to insure that the treated and untreated groups were comparable except for HGH replacement. Adverse events related to tumor growth and malignancy did not differ significantly between those treated and those not treated. Cardiovascular disease caused 36% of deaths in the treated group and 67% of deaths in the group that did not receive HGH. Cancer occurred in 1.6% of the treated group and 2.7% of the untreated group. Statistical analysis did not reveal any significant difference in adverse events between the treated and untreated group
Hunt KJ, LukanovaA, Rinaldi S, Lundin E, Norat T, Palmqvist R, Stattin P, Riboli E, Hallmans G, Kaaks R. A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study. Ann Epidemiol. 2006 Jul;16(7):563-71. Division of Clinical Epidemiology, University ofTexas Health Science Center, San Antonio, TX, USA. Higher risk of hypertension, esp. high diastolic blood pressure, was related to lower IGF-1 levels from 30 to 62 years of age
Halhali A, Villa AR, Madrazo E, Soria MC, Mercado E, Daaz L, Avila E, Garabadian M, Larrea F. Longitudinal changes in maternal serum 1,25-dihydroxyvitamin D and insulin like growth factor I levels in pregnant women who developed preeclampsia: comparison with normotensive pregnant women. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):553-6. Departamento de Biologna de la Reproduccia, Instituto Nacional de Ciencias Medicas y Nutrician Salvador Zubirain, Vasco de Quiroga No 15, Col.Tlalpan, C.P. 14000, Mexico DF, Mexico. Higher risk of high blood pressure (preeclampsia) correlated inversely with lower lGF-1 levels
Abdulle AM, Gillett MP, Abouchacra S, Sabri SM, Rukhaimi MA, Obineche EN, Singh J. Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients in pregnant women. Cell Biochem. 2007 Mar 27; Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, 17666, AI Ain, UAE,Risk of increased systolic and diastolic blood pressures correlated inversely with IGF-1 levels in hemodialysis patients
Ning Y, Williams MA, Vadachkoria S, Muy-Rivera M, Frederick I0, Luthy DA. Maternal plasma concentrations of insulin like growth factor-1 and insulin like growth factor-binding protein-1 in early pregnancy and subsequent risk of preeclampsia. Clin Biochem. 2004 Nov;37(11):968-73. Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, WA, USA.
Arterial hypertension during pregnancy (preeclampsia) inversely correlated with lGF-1 levels in pregnant women
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702-5803, USA. Vasan RS, Sullivan LM, D'Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, Wilson pw. Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study. Ann Intern Med. 2003 Oct 21 ;139(8):642-8 Cardiac failure is inversely correlated with lGF-1 levels in elderly men and women (mean age, 78.4 years) who did not have myocardial infarction and congestive heart failure at baseline
Juul A, Scheike T, Davidsen M, Gyllenborg J, JA,rgensen T. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case control study. Circulation. 2002 Aug 20; 1 06(8):939-44. Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Risk of ischemic heart disease increases with lowerlGF-1 levels in adult men and women
Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004 Jan;89(1 ):114-20. Department of Family and Preventive Medicine, University of California-San Diego School of Medicine, La Jolla, California 92093-0607. Risk of ischemic heart disease mortality increases with lower IGF-1 levels in elderly men and postmenopausal women, aged 51-98 years
Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7. Unit of Internal Medicine, Department of Experimental and Clinical Medicine G. Salvatore, University Magna Graecia of Catanzaro, Italy Risk of heart disease (increased left ventricular hypertrophy) inversely correlates with lGF-1 levels in never-treated hypertensive patients
Tong PC, Ho CS, Yeung VT, Ng MC, So WY, Ozaki R, Ko GT, Ma RC, Poon E, Chan NN, Lam CW, Chan JC. Association of testosterone, insulin-like growth factor-I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes. J Clin Endocrinol Metab. 2005 Dec;90(12):6418-23. Department of Medicine and Therapeutics, School of Public Health, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong.
Risk of metabolic syndrome-X correlates inversely with lGF-1 levels in middle-aged men (mean age 39 to 44 yrs)
Kim KR, Nam SY, Song YD, Lim SK, Lee HC, Huh KB . Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. Horm Res 1999;51(2):78-84. Division of Endocrinology, Department of Internal Medicine, YongDong Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Impaired secretion of HGH in obesity results in the consequent loss of the lipolytic effect of HGH. In a 12-week randomized, double-blind and placebo-controlled trial HGH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment.
Hunt KJ, Lukanova A, Rinaldi S, Lundin E, Norat T, Palmqvist R, Stattin P, Riboli E, Hallmans G, Kaaks R. A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study. Ann Epidemiol. 2006 Jul;16(7):563-71. Division of Clinical Epidemiology, University of Texas Health Science Center, San Antonio, TX, USA. Two-hour glucose level after glucose intake correlates inversely with lGF-1 levels in men and women aged 30 to 62 years
Dills DG, Moss SE, Klein R, Klein BE, Davis M. Is insulin-like growth factor I associated with diabetic retinopathy? Diabetes. 1990 Feb;39(2):191-5. Department of Medicine, University of Wisconsin School of Medicine, Madison 53792.
Risk of diabetes (increased glycosylated hemoglobin) increases with lower lGF-1 levels in adult (~ 18 yr old) diabetics with early-onset (diagnosed before 30 yr of age) and insulin dependent diabetes.
Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet. 2002 May 18;359(9319): 1740-5. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK. Risk of glucose intolerance or type 2 diabetes correlates inversely with lGF-1 levels in healthy men and women aged 45-65 years initially with normal glucose levels
Qiu C, Vadachkoria S, Meryman L, Frederick 10, Williams MA. Maternal plasma
concentrations of IGF-1, IGFBP-1, and C-peptide in early pregnancy and subsequent risk of gestational diabetes mellitus. Am J Obstet Gynecol. 2005 Nov; 193(5): 1691-7. Center for Perinatal Studies, Swedish Medical Center, Seattle, WA 98122, USA.
Risk of diabetes during pregnancy (gestational diabetes) correlates with lower lGF-1 levels in pregnant women
Maison P, Balkau B, Souberbielle JC, Cunin P, Vol S, Macquin-Mavier I, Eschwage E; the D. E. S. I. R. Study Group. Evidence for distinct effects of GH and IGF-I in the metabolic syndrome. Diabet Med. 2007 May 29; Service de Pharmacologie Clinique, and Unitsit de Recherche Clinique, AP-HP, Hospital Henri Mondor, Universitate Paris XlI Cracteil, France Risk of higher fasting glucose at lower normal IGF-1 levels in men and women aged 30-64 years
Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7. Unit of Internal Medicine, Department of Experimental and Clinical Medicine G. Salvatore, University Magna Graecia of Catanzaro, Italy Risk of increased blood levels of insulin (hyperinsulinemia and glucose intolerance) correlates inversely with IGF-1 levels in never-treated hypertensive patients
Ong KK, Petry CJ, Emmett PM, Sandhu MS, Kiess W, Hales CN, Ness AR, Dunger DB; ALSPAC study team. Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia. 2004 Jun;47 (6): 1 064-70. Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Level 8, Box 116, Cambridge CB2 2QQ, UK.
Higher risk of lower insulin secretion after glucose intake at with lower lGF-1 levels in normal children
C. Other Age-Related diseases and Metabolic States associated with lower IGF-1 within Reference Ranges
Zs-Nagy I. Is consensus in anti-aging medical intervention an elusive expectation or a realistic goal? Arch Gerontol Geriatr. 2009 May-Jun;48(3):271-5. Epub 2009 Mar 9.
"The facts known about the adult growth hormone deficiency (AGHD) syndrome and the beneficial effects of hGHRT in all aspects of this pathology suggest that aging may generally be considered as an AGHD syndrome."
Caregaro L, Alberino F, Amodio P, Merkel C, Angeli P, Plebani M, Bolognesi M, Gatta A. Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis. Nutrition. 1997 Mar; 13(3): 185-90. Department of Clinical and Experimental Medicine, University of Padua, Italy Severity of liver cirrhosis correlates inversely with IGF-1 levels with chronic liver disease.
Stuver SO, Kuper H, Tzonou A. Lagiou P, Spanos E, Hsieh CC, Mantzoros C, Trichopoulos D. Insulin-like growth factor 1 in hepatocellular carcinoma and metastatic liver cancer in men. Int J Cancer. 2000 Jul 1 ;87(1):118-21. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Severity of liver cancer increases with lower IGF-1 levels in patients with liver cancer
Fabris N, Mocchegiani E, Muzzioli M, Piloni S. Recovery of age-related decline of thymic endocrine activity and PHA response by lysin-arginine combination. Int J Immunopharmacol. 1986;8(7):677-85. Provoking secretion of growth hormone produced almost a full recovery in the secretion of immunity related thymic hormones, even at a very old age
Monroe WE, Roth JA, Grier RL, Arp LH, Naylor PH. Effects of growth hormone on the adult canine thymus. Thymus. 1987;9(3):173-87. Regeneration of age-associated atrophy of thymus and T-cell related immunity with exogenous HGH
Crist DM, Peake GT, Mackinnon LT, Sibbitt WL Jr, Kraner JC. Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion. Metabolism. 1987 Dec;36(12):1115-7. Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131. Growth-hormone-treated women increased their level of T-killer-cell immunity by 20 percent
Szulc P, Joly-Pharaboz MO, Marchand F, Delmas PD. Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study. Calcif Tissue Int. 2004 Apr;74(4):322-9. INSERM 403 Research Unit, Hospital Edouard Herriot, 69437 Lyon, France. Hip bone mineral density increases relative to IGF-1 levels in men less than 60 years of age
Rhee EJ, Oh WV, Lee WY, Kim SW, Oh ES, Baek KH, Kang MI, Park CY, Choi MG, Yoo HJ, Park SW. Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men. J Bone Miner Metab. 2004;22(4):392-8. Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea. Risk of lower bone density, especially femoral bone density correlates inversely with IGF-1 in healthy middle-aged men
Amato G, Izzo G, Montagna GL, Bellastella A. Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects. Clinical Endocrinology 1996 45:27-32. Department of Endocrinology, Second University of Naples, Naples, Italy Approximately 2 units of rHGH were administered daily by injection for 12 months. All patients had objective, measured evidence of osteoporosis before therapy. Bone protein matrix doubled during therapy to completely normal levels. Twelve months of therapy were required to bring slow gradual reversal of osteoporosis. When therapy was discontinued, benefits were slowly lost over the subsequent 12 months.
Clemmesen B, Overgaard K, Riis B, Christiansen C. Human growth hormone and growth hormone releasing hormone: a double-masked, placebo-controlled study of their effects on bone metabolism in elderly women. Osteoporos Int 1993 Dec;3(6):330-6. Center for Clinical and Basic Research, Ballerup, Denmark. Reversal of osteoporosis in otherwise normal elderly women using HGH
Leal-Cerro A, Povedano J, Astorga R, Gonzalez M, Silva H, Garcia-Pesquera F, Casanueva FF, Dieguez C. The growth hormone (GH)-releasing hormone (GHRH), insulin-like growth factor-1 axis in patients with fibromyalgia syndrome. J Clin Endocrinol Metab. 1999 Sep;84(9):3378-81 Fibromyalgia patients exhibit marked decrease in GH secretion. It is postulated that this might be one cause of that syndrome.
Nakaoka 0, Sugimoto T, Kaji H, Kanzawa M, Yano S, Yamauchi M, Sugishita T, Chihara K. Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women. Osteoporos Int. 2001; 12(7):548-54. Department of Medicine, Kobe University School of Medicine, Japan.Risk of bone mineral density and osteoporotic spinal fractures increases with lower IGF-1 levels in postmenopausal Japanese women aged 48-84 years (mean age 64 years)
Gamero P, Sornay-Rendu E, Delmas PD. Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet. 2000 Mar 11 ;355(9207):898-9 .Risk of osteoporotic fractures correlates inversely with IGF-1 in healthy postmenopausal women
Foldes J, Lakatos P, ZsadAinyi J, HorvAith C. Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism. Eur J Endocrinol. 1997 Mar;136(3):277-81. First Department of Medicine, Semmelweis University, Budapest, Hungary Risk of lower bone mineral density (BMD) of the femoral neck correlates inversely with lGF-1 in postmenopausal women with subclinical hyperthyroidism.
Gomez JM, Maravall FJ, GA3mez N, Navarro MA, Casamitjana R, Soler J. Relationship between 25-(OH) D3, the IGF-I system, leptin, anthropometric and body composition variables in a healthy, randomly selected population. Horm Metab Res. 2004 Jan;36(1):4853. Endocrinology Service and Hormonal Laboratory, Hospital Clinic, Barcelona,
Vitamin D3 deficiency correlates inversely with IGF-1 levels in men. Conversion of cholecalciferol to to 25-OH D3 seems related to IGF-1.
Roubenoff R, Parise H, Payette HA, Abad LW, D'Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med. 2003 Oct 15;115(6):429-35. United States Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. All cause mortality and death rate increases with lower lGF-1 in very old community-dwelling men and women.
Denti L, Annoni V, Cattadori E, Salvagnini MA, Visioli S, Merli MF, Corradi F, Ceresini G, Valenti G, Hoffman AR, Ceda GP. Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. Am J Med. 2004 Sep 1 ;117(5):312-7. Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, Parma, Italy. Mortality in stroke patients correlates inversely with IGF-1 levels in stroke patients.
Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SO, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):1829-37. Cardiology Department, Military Hospital, ul. Weigla 5, 50-981 Wroclaw, Poland. Ewa Mortality and death rate increase as IGF-1 declines at levels in men with chronic heart failure.
Fernandez-Reyes MJ, Alvarez-Ude F, Sanchez R, Mon C, Iglesias P, Dlez JJ, Vazquez A. Inflammation and malnutrition as predictors of mortality in patients on hemodialysis. J Nephrol. 2002 Mar-Apr;15(2):136-43. Servicio de Nefrologia, H. General, Segovia, Spain. Morality correlates inversely with lGF-1 levels in hemodialysis patients
Petretta M, Colao A, Sardu C, Scopacasa F, Marzullo P, Pivonello R, Fontanella L, de Caterina M, de Simone A, Bonaduce D. NT-proBNP, IGF-I and survival in patients with chronic heart failure. Growth Horm IGF Res. 2007 Mar 22; Department of Internal Medicine, Cardiology, Heart and Immunological Sciences, Section of Internal Medicine, University of Naples Federico, Italy. Mortality correlates with declining IGF-1 and IGF -I/GH ratio levels in patients with chronic heart failure
Zaccaria M, Varnier M, Piazza P, Noventa D, Ermolao A. Blunted growth hormone response to maximal exercise in middle-aged versus young subjects and no effect of endurance training. J Clin Endocrinol Metab 1999 Jul;84(7):2303-7. Department of Medical and Surgical Sciences, University of Padua, Italy. This is a study of HGH secretion increases in response to exercise in healthy young people. Five young athletic men, average age 21, in response to 4 months of daily exhaustive physical conditioning were compared to 7 healthy middle aged men, average age 42, under similar conditions. The release of pituitary GH in response to exercise had decreased greatly in the older group. On direct measurement, HGH levels (not IGF-1 but HGH itself) increased to an average of 57 mcg/L in the younger group, but increased with exercise to only 8.1 in the older group. That represents an 85% reduction by age 42 in pituitary GH release following exercise.
Johannsson G, Mårin P, Lönn L, Ottosson M, Stenlöf K, Björntorp P, Sjöström L, Bengtsson BA. Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab. 1997 Mar;82(3):727-34. Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden. 30 men, ages 48-66, with the symptoms of syndrome X were studied. These men were treated for 9 months with physiologic doses of human growth hormone or placebo in a double-blind trial. The men receiving the HGH had the following improvements: visceral fat decreased by 18%, subcutaneous fat decreased by 6%, insulin sensitivity improved by 21%, diastolic blood pressure declined by 5 mm Hg, total serum cholesterol dropped by 11%, and serum triglycerides dropped 15%. No changes were noted in the men receiving placebos.
D. Other Supporting data on growth hormone's beneficial effects in adults:
1) GH is important for psychic well-being
Studies Below Show Lower Quality of Life and Increased Senescence with lower GH and/or IGF-1 levels
Carroll, P.V., Christ, E.R., Bengtsson, B.A., Carlsson, L., Christiansen, J.S., et al.(1998). Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A review. The Journal of Clinical Endocrinology & Metabolism, 83(2), 382-395. Conclusions: The importance of GH throughout adult life is now unequivocally accepted. GH deficiency is recognized to result in deteriorations in metabolism, psychological well-being, and overall quality of life. Many of these alterations can be improved or corrected with GH replacement.
Verhelst, J., Abs, R., Vandeweghe, M., Mockel, J., Legros, J.J., Copinschi, G., et al. (1997). Two years of replacement therapy in adults with growth hormone deficiency. Clinical Endocrinology (Oxford), 47(4), 485-494. Adults treated with human growth hormone (hGH) replacement therapy for two years experienced beneficial effects on metabolic parameters and improvement of overall general sense of well-being and quality of life.
Gilchrist FJ, Murray RD, Shalet SM. The effect of long-term untreated growth hormone defiCiency (GHD) and 9 years of GH replacement on the quality of life (QoL) of GH-deficient adults. Clin Endocrinol (Oxf). 2002 Sep;57(3):363-70 Adults treated with human growth hormone (HGH) replacement therapy for two years experienced beneficial effects on metabolic parameters and improvement of overall general sense of well-being and quality of life
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML; Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006 May;91(5):1621-34. Epub 2006 Apr 24. Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures. The risks of GH treatment are low. GH dosing regimens should be individualized.
Baum HB, Biller BM, Finkelstein JS, Cannistraro KB, Oppenhein DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med. 1996 Dec 1;125(11):883-90. Neuroendocrine Unit, Massachusetts General Hospital, Boston 02114, USA. Growth hormone administered to men with adult-onset growth hormone deficiency increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects.
Abs R, Bengtsson BA, Hernberg-Stahl E, Monson JP, Tauber JP, Wilton P, Wuster C. GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin Endocrinol (Oxf). 1999 Jun;50(6):703-13
Murray RD, Skillicorn CJ, Howell SJ, Lissett CA, Rahim A, Shalet SM. Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults. Clin Endocrinol (Oxf). 1999 Jun;50(6):749-57
Studies Below Showed Depression associated with lower GH and/or IGF-1 levels
Jarrett DB, Miewald JM, Kupfer DJ. Recurrent depression is associated with a persistent reduction in sleep-related growth hormone secretion. Arch Gen Psychiatry. 1990 Feb;47(2): 113-8
Jarrett DB, Kupfer DJ, Miewald JM, Grochocinski VJ, Franz B. Sleep-related growth hormone secretion is persistently suppressed in women with recurrent depression: a preliminary longitudinal analysis. J Psychiatr Res. 1994 May-Jun;28(3):211-23)
Rubin RT, Poland RE, Lesser 1M. Neuroendocrine aspects of primary endogenous depression: Serum growth hormone measures in patients and matched control subjects. Bioi Psychiatry. 1990 May 15;27(10):1065-82
Schilkrut R, Chandra 0, Osswald M, Ruther E, Baafusser B, Matussek. Growth hormone release during sleep and with thermal stimulation in depressed patients. Neuropsychobiology. 1975;1(2):70-9
Barry S, Dinan TG. Neuroendocrine challenge tests in depression: a study of growth hormone, TRH and cortisol release. J Affect Disord. 1990 Apr; 18(4):229-34
Dinan TG, Barry S. Responses of growth hormone to desipramine in endogenous and nonendogenous depression. Br J Psychiatry. 1990 May;156:680-4
Voderholzer U, Laakmann G, Wittmann R, Daffner-Bujia C, Hinz A, Haag C, Baghai T. Profiles of spontaneous 24-hour and stimulated growth hormone secretion in male patients with endogenous depression. Psychiatry Res. 1993 Jun;47(3):215-27
Harro J, Rimm H, Harro M, Grauberg M, Karelson K, Viru AM. Association of depressiveness with blunted growth hormone response to maximal physical exercise in young healthy men. Psychoneuroendocrinology. 1999 Jul;24(5):505-17
Greden JF. Biological markers of melancholia and reclassification of depressive disorders. Encephale. 1982;8(2): 193-202
McMillan CV, Bradley C, Gibney J, Healy ML, Russell-Jones DL, Sonksen PH. Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency. Clin Endocrinol. (Oxf). 2003 Oct;59(4):467-75
Studies Below Show Increased Anxiety Associated with lower GH and/or IGF-1 levels
Tancer ME, Stein MB, Uhde TW. Growth hormone response to intravenous clonidine in social phobia: comparison to patients with panic disorder and healthy volunteers. Bioi Psychiatry. 1993 Nov 1 ;34(9):591-5
Cameron OG, Abelson JL, Young EA. Anxious and depressive disorders and their comorbidity: effect on central nervous system noradrenergic function. Biol Psychiatry. 2004 Dec 1 ;56(11 ):875-83
Stabler B. Impact of growth hormone (GH) therapy on quality of life along the lifespan of GH-treated patients. Harm Res. 2001 ;56 Suppl 1 :55-8
Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC. Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatry. 1991 Feb;48(2):15762
Studies Below Show Increased Memory loss and Alzheimer's Disease Associated with lower GH and/or IGF-1 levels
Deijen JB, de Boer H, Blok GJ, van der Veen EA. Cognitive impairments and mood disturbances in growth hormone deficient men. Psychoneuroendocrinology. 1996 Apr;21 (3):313-22
Rollero A, Murialdo G, Fonzi S, Garrone S, Gianelli MV, Gazzerro E, Barreca A, Polleri A. Relaionship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects. Neuropsychobiology. 1998;38(2):73-9
van Dam PS, de Winter CF, de Vries R, van der Grond J, Drent ML, Lijffijt M, Kenemans JL, Aleman A, de Haan EH, Koppeschaar HP. Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate. Psychoneuroendocrinology. 2005 May;30(4):357-63
Watanabe T, Koba S, Kawamura M, Itokawa M, Idei T, Nakagawa Y, Iguchi T, Katagiri T. Small dense low-density lipoprotein and carotid atherosclerosis in relation to vascular dementia. Metabolism. 2004 Apr;53(4):476-82
Study Below Shows Sleep disorders Associated with Lower GH and/or IGF-1 levels
Astrom C, Lindholm J. Growth hormone-deficient young adults have decreased deep sleep. Neuroendocrinology. 1990 Jan;51 (1 ):82-4
Studies Showing Loss of Sexual Function and/or Potency Associated with Lower GH and/or IGF-1 levels
Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Brabant G, Jonas U. Serum levels of human growth hormone during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction. Urology. 2002 Apr;59(4):609-14
Huang X, Li S, Hu L. Growth hormone deficiency and age-related erectile dysfunction. Zhonghua Nan Ke Xue. 2004 Nov;10(11):867
Studies Showing Deteriorating Physical Condition and Body Composition Associated with Lower GH and/or IGF-1 levels
Sartorio A, Narici MV. Growth hormone (GH) treatment in GH-deficient adults: effects on muscle size, strength and neural activation. Clin Physiol 1994 Sep;14(5):527-37
De Boer H, Blok GJ, Voerman HJ, De Vries PM, van der Veen EA. Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. J Clin Endocrinol Metab 1992 Sep;75(3):833-7
Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 1991 Feb;70(2):688-94
De Boer H, Blok GJ, Voerman HJ, De Vries PM, van der Veen EA. Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. J Clin Endocrinol Metab. 1992 Sep;75(3):833-7
Khansari DN, Gustad T. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice. Mech Ageing Dev. 1991 Jan;57(1):87-100. Department of Veterinary Science/Microbiology, North Dakota State University, Fargo 58105. Aging growth-hormone-treated mice had decreased mortality and survived far beyond the outer limits of mouse longevity. Immune production of T-cells was comparable to that of young mice.
Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1-6. Department of Medicine, Medical College of Wisconsin, Milwaukee. Increased in bone density, conversion of fat to lean body mass, reversal of age-related skin atrophy with HGH therapy.
ter Maaten JC, de Boer H, Kamp O, Stuurman L, van der Veen EA. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab 1999 Jul;84(7):2373-80. Department of Endocrinology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. 38 adult men with a deficiency of growth hormone were treated with HGH replacement and followed for 3 to 5 years. Their doses averaged 2.3 units/day. Stroke volume of the heart increased 16%, cardiac output increased 33%. Bone density increased up to16%. Subcutaneous fat decreased 33%, and abdominal fat decreased by 46%. This study shows that HGH benefits osteoporosis and improves heart function.
Studies Below Show Benefit and Safety of Long Term Treatment
Ogilvy-Stuart AL, Ryder WD, Gattamaneni HR, Clayton PE, Shalet SM. Growth hormone and tumour recurrence. BMJ. 1992 Jun 20;304(6842):1601-5. Department of Endocrinology, Christie Hospital and Holt Radium Institute, Manchester. No increase in malignancy or neoplasm was detected with long-term HGH therapy
Arvat E, Ceda G, Ramunni J, Lanfranco F, Aimaretti G, Gianotti L, Broglio F, Ghigo E. The IGF-I response to very low rHGH doses is preserved in human ageing. Clin Endocrinol (Oxf) 1998 Dec;49(6):757-63. Department of Internal Medicine, University of Turin. Sensitivity of body tissues to HGH is preserved, and perhaps even increased with age, despite the reduction of internal pituitary secretion. When given 1 unit of rHGH by injection daily for 4 days: In a young group, average age 29, with a baseline average IGF-1 of 230, it increased to 301 after the series of 1-unit HGH injections. In an elderly group, average age 69, with average baseline IGF-1 of 123, IGF-1 increased to 208 after a series of daily 1-unit injections. [A consistent finding in recent published studies is that IGF-1 increases by approximately 80 ng/ml for each one unit injected daily, and that levels achieving 200 or higher results in better clinical benefit.]
Cuneo RC, Judd S, Wallace JD, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley D. J. The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults. Clin Endocrinol Metab 1998 Jan;83(1):107-16. Endocrine Unit, Flinders Medical Centre, Adelaide, Australia. 160 GH deficient adults were studied. The replacement dose of injected rHGH was 2 units daily for one year. The authors concluded that this dose may be too high and that between 1 to 2 units daily, depending on body size, would be more physiological. Baseline IGF-1 average was 100 ng/ml before therapy (within normally reported reference ranges for elderly patients), increasing to average of 280 on treatment. Patients were evaluated for body composition, quality of life and safety of therapy. CONCLUSIONS: Substantial increases in lean tissue mass, skin, muscle and organs, occurred with simultaneous decrease in fat. Improvement was consistent in perceived quality of life. Statistically significant increases were measured in energy levels, decrease in pain, enhanced emotional well being, improved quality of sleep, and improvement in physical mobility. Improvements also occurred in risk factors for atherosclerosis, with lowering of LDL cholesterol. Therapy was found to be safe. The one significant side effect was fluid retention in some patients during the first month or so of treatment, which disappeared with continued therapy.
Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer? Clin Endocrinol (Oxf). 2006 Feb;64(2):115-21. Departments of Endocrinology, St Bartholomew's Hospital, London, UK.Extensive studies of the outcome of GH replacement in childhood cancer survivors show no evidence of an excess of de novo cancers, and more recent surveillance of children and adults treated with GH has revealed no increase in observed cancer risk
Fradkin, J. E., et al. Risk of leukemia after treatment with pituitary growth hormone, Journal of the American Medical Association, 1993; 270: 2829-2832
Wiren L, Bengtsson BA, Johannsson G. Beneficial effects of long-term GH
replacement therapy on quality of life in adults with GH deficiency. Clin Endocrinol (Oxf) 1998 May;48(5):613-20. Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.160 growth adults received rHGH replacement treatment by injection. They were carefully followed and evaluated periodically for several years for benefit, including overall health, physical and mental well-being. Using a standardized Health Profile testing and also an index of Generalized Psychological Well-Being it was found that all areas improved significantly. Improvements often occurred slowly, but patients continued to improve for several years after beginning treatment. Some patients did not notice any benefit for the first few months, but benefit was progressive for several years thereafter. 93% of patients demonstrated positive effects. Beneficial effects of GH therapy on quality of life are sustained during long-term therapy.
2) GH Replacement may Protect—at least partially—Against the Appearance of Age-Related Diseases
Studies Below Show Increasing Hypercholesterolemia Associated with Lower GH and/or IGF-1 levels
Abdu TA, Neary R, Elhadd TA, Akber M, Clayton RN. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities. Clin Endocrinol (Oxf) 2001 Aug;55(2):209-16
Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lindstedt G, Lundberg PA, Bengtsson BA. Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf). 1994 Sep;41 (3):351-7
Sanmarti A, Lucas A, Hawkins F, Webb SM, Ulied A. Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status.status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol. 1999 Nov;141 (5):481-9
Colao A, di Somma C, Pivonello R, Cuocolo A, Spinelli L, Bonaduce 0, Salvatore M, Lombardi G. The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J Clin Endocrinol Metab. 2002 Mar;87(3):1088-93.
Studies Below Show Increasing Atherosclerosis and Cardiovascular Diseases Associated with Lower GH and/or IGF-1 levels
Capaldo B, Patti L, Oliviero U, Longobardi S, Pardo F, Vitale F, Fazio S, Di Rella F, Biondi B, Lombardi G, Sacca L. Increased arterial intima-media thickness in childhood-onset growth hormone deficiency. J Clin Endocrinol Metab. 1997 May;82(5):1378-81
Markussis V, Beshyah SA, Fisher C, Sharp P, Nicolaides AN, Johnston DG. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet. 1992;340:1188-1192.
Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab. 1999 Feb;84(2):453-7
Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lundstedt G, Lundberg PA, Bengtssopn BA. Serum insulin-like growth factor 1 in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf). 1994 Sep;41 (3):351-7
Conti E, Andreotti F, Sciahbasi A, Riccardi P, Marra G, Menini E, Ghirlanda G, Maseri A. Markedly reduced insulin-like growth factor-1 in the acute phase of myocardial infarction. J Am Col Cardiol. 2001 Jul;38(1 ):26-32
Rudman 0, Nagraj HS, Mattson DE, Jackson DL, Rudman IW, Boswell J, Pucci DC. Hyposomatomedinemia in the men of a Veterans Administration Nursing Home
revalence and correlates. Gerontology. 1987;33(5):307-14
Studies Below Show Increasing Obesity Associated with Lower GH and/or IGF-1 levels
Kavya C. Mekala and Nicholas A. Tritos. Effects of Recombinant Human Growth Hormone Therapy in Obesity in Adults: A Metaanalysis. J Clin Endocrinol Metab. January 2009, 94(1):130–137. Division of Internal Medicine (K.C.M., N.A.T.) and Department of Endocrinology (N.A.T.), Lahey Clinic Medical Center, Burlington, Massachusetts 01805; and Tufts University School of Medicine (K.C.M., N.A.T.), Boston, Massachusetts 02111. rhGH therapy leads to decrease in visceral adiposity and increase in lean body mass as well as beneficial changes in lipid profile in obese adults, without inducing weight loss.
Beshyah SA, Freemantle C, Thomas E, Rutherford 0, Page B, Murphy M, Johnston DG. Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults. Clin Endocrinol (Oxf) 1995 Feb;42(2):179-89
Attanasio AF, Bates PC, Ho KK, Webb SM, Ross RJ, Strasburger CJ, Bouillon R, Crowe B, Selander K, Valle 0, Lamberts SW; Hypoptiuitary Control and Complications Study International Advisory Board. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status—3-year results from the HypoCCS Database. J Clin Endocrinol Metab. 2002 Apr;87(4):1600-6
Stouthart PJ, de Ridder CM, Rekers-Mombarg L T, van der Waal HA. Changes in body composition during 12 months after discontinuation of growth hormone therapy in young adults with growth hormone deficiency from childhood. J Pediatr Endocrinol Metab. 1999 Apr;12 Suppl1 :335-8
Biller BM, Sesmilo G, Baum HB, Hayden 0, Schoenfeld 0, Klibanski A. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab. 2000 Mar;85(3):970-6
Kohno H, Ueyama N, Honda S. Unfavourable impact of growth hormone (GH) discontinuation on body composition and cholesterol profiles after the completion of height growth in GH-deficient young adults. Diabetes Obes Metab. 1999 Sep;1(5):293-6
Kuromaru R, Kohno H, Ueyama N, Hassan HM, Honda S, Hara T. Long-term prospective study of body composition and lipid profiles during and after growth hormone (GH) treatment in children with GH deficiency: gender-specific metabolic effects. J Clin Endocrinol Metab. 1998 Nov;83(11 ):3890-650.
Vahl N, Juul A, Jorgensen JO, Orskov H, Skakkebaek NE, Christiansen JS. Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study. J Clin Endocrinol Metab. 2000 May;85(5):1874-81
Norrelund H, Vahl N, Juul A, Moller N, Alberti KG, Skakkebaek NE, Christiansen JS, Jorgensen JO. Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism. J Clin Endocrinol Metab. 2000 May;85(5): 1912-7
Johannsson G. What happens when growth hormone is discontinued at completion of growth? Metabolic aspects. J Pediatr Endocrinol Metab. 2000;13 Suppl 6:1321-6
Gill MS, Toogood AA, Jones J, Clayton PE, Shalet SM. Serum leptin response to the acute and chronic administration of growth hormone (GH) to elderly subjects with GH deficiency. J Clin Endocrinol Metab 1999 Apr;84(4):1288-95. Endocrine Sciences Research Group, Department of Medicine, University of Manchester, United Kingdom.
HGH injection increases leptin secretion in elderly GH deficient adults. Leptin is a hormone that reduces body fat.
Study Below Shows Insulin Resistance Associated with Lower GH and/or IGF-1 levels
Nam SY, Kim KR, Cha BS, Song YO, Lim SK, Lee HC, Huh KB. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Int J Diabetes Relat Metab Disord. 2001 Aug;25(8):1101-7
Studies Below Show Rheumatoid Diseases and Fibromyalgia Associated with Lower GH and/or IGF-1 levels
Neidel J. Changes in systemic levels of insulin-like growth factors and their binding proteins in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2001 Jan-Feb;19(1 ):81-4
Bagge E, Bengtsson BA, Carlsson L, Carlsson J. Low growth hormone secretion in patients with fibromyalgia—a preliminary report on 10 patients and 10 controls. J Rheumatol. 1998 Jan;25(1):145-8
Studies Below Show Osteoporosis Associated with Lower GH and/or IGF-1 levels
Foldes J, Lakatos P, Zsadanyi J, Horvath C. Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism. Eur J Endocrinol. 1997 Mar; 136(3):277-81
Monson JP, Abs R, Bengtsson BA, Bennmarker H, Feldt-Rasmussen U, Hernberg-Stahl E, Thoren M, Westberg B, Wilton P, Wuster C. Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS Study Group and the KIMS International Board. Pharmacia and Upjohn International Metabolic Database. Clin Endocrinol (Oxf). 2000 Sep;53(3):281-9
Longobardi S, Di Rella F, Pivonello R, Di Somma C, Klain M, Maurelli L, Scarpa R, Colao A, Merola B, Lombardi G. Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients. J Endocrinol Invest. 1999 May;22(5):333-9
Beckers V, Milet J, Legros JJ. Prolonged treatment with recombined growth hormone improves bone measures: study of body composition in 21 deficient adults on treatment. Ann Endocrinol (Paris). 2001 Dec;62(6):507-15
Gomez JM, Gomez N, Fiter J, Soler J. Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res. 2000 Feb;32(2):66-70
Kaufman JM, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab. 1992 Jan;74(1):118-23
Calo L, Castrignano R, Davis PA, Carraro G, Pagnin E, Giannini S, Semplicini A, D'Angelo A. Role of insulin-like growth factor-I in primary osteoporosis: a correlative study. J Endocrinol Invest. 2000 Apr;23(4):223-7
Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. 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
Nakaoka 0, Sugimoto T, Kaji H, Kanzawa M, Yano S, Yamauchi M, Sugishita T, Chihara K. Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women. Osteoporos Int. 2001; 12(7):548-54
Rico H, Del Rio A, Vila T, Patino R, Carrera F, Espinos D. The role of growth hormone in the pathogenesis of postmenopausal osteoporosis. Arch Intern Med. 1979 Nov;139(11): 1263-5
Ljunghall S, Johansson AG, Burman P, Kampe 0, Lindh E, Karlsson FA. Low plasma levels of insulin-like growth factor 1 (lGF-1) in male patients with idiopathic osteoporosis. J Intern Med. 1992 Jul;232(1 ):59-64
Studies Below Show Increased Risk of Infection and Lower Immunity Associated with Lower GH and/or IGF-1 levels
Crist, D. M., et al. "Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion," Metabolism, 1987; 36 (12): 1115-1117.
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Manfredi R, Tumietto F, Azzaroli L, Zucchini A, Chiodo F, Manfredi G. Growth hormone (GH) and the immune system: impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH. J Pediatr Endocrinol. 1994 Jul-Sep;7(3):245-51
Mynarcik DC, Frost RA, Lang CH, DeCristofaro K, McNurlan MA, Garlick PJ, Steigbigel RT, Fuhrer J, Ahnn S, Gelato MC. Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration. J Acquir Immune Defic Syndr. 1999 Sep 1 ;22(1 ):49-55
Panamonta 0, Kosalaraksa P, Thinkhamrop B, Kirdpon W, Ingchanin C, Lumbiganon P. Endocrine function in thai children infected with human immunodeficiency virus. J Pediatr Endocrinol Metab. 2004 Jan;17(1):33-40
Gupta KL, Shetty KR, Agre JC, Cuisinier MC, Rudman IW, Rudma n D. Human growth hormone effect on serum IGF-I and muscle function in poliomyelitis survivors. Arch Phys Med Rehabil. 1994 Aug;75(8):889-94
Crist DM, Kraner JC. Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion. Metabolism. 1990 Dec;39(12):1320-4
Peake GT, Mackinnon L T, Sibbitt WL Jr, Kraner JC. Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion. Metabolism. 1987 Dec;36(12):1115-7
Vara-Thorbeck R, Guerrero JA, Rosell J, Ruiz-Requena E, Capitan JM. Exogenous growth hormone: effects on the catabolic response to surgically produced acute stress and on postoperative immune function. World J Surg. 1993 Jul-Aug;17(4):530-7
Studies Below Show Increased Risk of Cancer Associated with Lower GH and/or IGF-1 levels
Woodson K, Tangrea JA, Pollak M, Copeland TD, Taylor PR, Virtamo J, Albanes D. Serum IGF•1: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Res. 2003 JuI15;63(14):3991-4
Baffa R, Reiss K, EI-Gabry EA, Sedor J, Moy ML, Shupp-Byrne D, Strup SE, Hauck WW, Baserga R, Gomella LG. Low serum insulin-like growth factor 1 (IGF-1): a significant association with prostate cancer. Tech Urol. 2000 Sep;6(3):236-9
Chokkalingam AP, Pollak M, Fillmore CM, Gao YT, Stanczyk FZ, Deng J, Sesterhenn lA, Mostofi FK, Fears TR, Madigan MP, Ziegler RG, Fraumeni JF Jr, Hsing AW. Insulin-like growth factors and prostate cancer: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 2001 May;10(5):421-7
Colombo F, lannotta F, Fachinetti A, Giuliani F, Cornaggia M, Finzi G, Mantero G, Fraschini F, Malesci A, Bersani M, et al. Changes in hormonal and biochemical parameters in gastric adenocarcinoma. Minerva Endocrinol. 1991 Jul-Sep;16(3):127-39
3) Low growth hormone may be associated with shorter lifespan:
Studies Below Show Shorter Life Expectancy Associated with Lower GH and/or IGF-1 levels
Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4;336(8710):285-8 mortality rate nearly doubles: 1.82
Besson A, Salemi S, Gallati S, Jenal A, Horn R, Mullis PS, Mullis PE. Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab. 2003 Aug;88(8):3664-7
Bates AS, Van't Hoff W, Jones PJ , Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169-72
Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997 Jan;46(1):75-81 Mortality rate doubles: 2.17 X with lower growth hormone
Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004 Jul;89(7):3306-12
Bengtsson BA, Koppeschaar HP, Abs R, Bennmarker H, Hernberg-Stahl E, Westberg B, Wilton P, Monson JP, Feldt-Rasmussen U, Wuster C. Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group. J Clin Endocrinol Metab. 1999 Nov;84(11):4291•2
Nilsson B, Gustavasson-Kadaka E, Bengtsson BA, Jonsson B. Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab. 2000;85:14201425. Mortality rate doubles: 2.02 with lower HGH levels
Tomlinson JW, Holden N, Hills RK, et al (West Midlands Prospective Hypopituitary Study Group). Association between premature mortality and hypopituitarism. Lancet. 2001 ;357:425-431 Mortality rate nearly doubles: 1.87 X with lower HGH levels
Roubenoff R, Parise H, Payette HA, Abad LW, D'Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community dwelling men and women: the Framingham Heart Study. Am J Med. 2003 Oct 15; 115(6):429-35.
Denti L, Annoni V, Cattadori E, Salvagnini MA, Visioli S, Merli MF, Corradi F, Ceresini G, Valenti G, Hoffman AR, Ceda GP. Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. Am J Med. 2004 Sep 1;117(5):312-7.
Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24; 114(17): 1829-37.
Fernandez-Reyes MJ, Alvarez-Ude F, Sanchez R, Mon C, Iglesias P, Diez JJ, Vazquez A. Inflammation and malnutrition as predictors of mortality in patients on hemodialysis. J Nephrol. 2002 Mar-Apr; 15(2): 136-43.
Petretta M, Colao A, Sardu C, Scopacasa F, Marzullo P, Pivonello R, Fontanella L, de Caterina M, de Simone A, Bonaduce D. NT-proBNP, IGF-I and survival in patients with chronic heart failure. Growth Horm IGF Res. 2007 Aug;17(4):288-96
Rasmuson T, Grankvist K, Jacobsen J, Olsson T, Ljungberg B. Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma. Acta Oncol. 2004;43(8):744-8.
Studies Below Show Adverse Symptoms of Persisting Lower GH and/or IGF-1 levels and Potential for Improvement with Replacement Therapy
Cuneo RC, Salomon F, McGauley GA, Sonksen PH. The growth hormone deficiency syndrome in adults. Clin Endocrinol (Oxf). 1992;37:387-97
Christ ER, Carroll PV, Russell JDL, Sonksen PH. The consequences of growth hormone deficiency in adulthood, and the effects of growth hormone replacement. Schweiz Med Wochenschr 1997; 127:1440-9
Labram EK, Wilkin T J. Growth hormone deficiency in adults and its response to growth hormone replacement. QJM. 1995;88:391-9
Rosen T, Johannsson G, Johansson JO, Bengtsson BA. Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. Horm Res. 1995;43:93-9
Jorgensen JO, Muller J, MolierJ, Wolthers T, Vahl N, Juul A, Skakkebaek NE, Christiansen JS. Adult growth hormone deficiency. Horm Res. 1994:42:235-241
Lieberman SA, Hoffman AR. Growth hormone deficiency in adults: characteristics and response to growth hormone replacement. J Pediatr. 1996; 128:S58-S60.
Mercado M, Espinosa de los Monteros AL, Sosa E, Cheng S, Mendoza V, Hernandez I, Sandoval C, Guinto G, Molina M. Clinical-biochemical correlations in acromegaly at diagnosis and the real prevalence of biochemically discordant disease. Horm Res. 2004;62(6):293-9.
Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, LucasMorante T, Moreno B, Obiols G, de Pablos P, Paramo C, Pico A, Torres E, Varela C, Vazquez JA, Zamora J, Albareda M, Gilabert M. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol. 2004 Oct;151 (4):439-46
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