INTRODUCTION

12 elderly men (aged 61-81) were injected daily with high levels of Human Growth Hormone (HGH). The results showed that there was a 9% increase in lean body mass and 14% decrease in fatty tissues. The men reported also an enhanced sense of well-being. HRT (hormone replacement therapy) has grown in popularity very much and not only HGH but other hormones (e.g. DHEA) have also become involved. There is, of course, no doubt that they help in some way or the other - they do increase muscle mass, bone mineral content and there is fat redistribution. And while many of the treated people report feeling better, double-blind studies on men aged 70 to 85 have shown no difference between test and placebo-controlled subjects. Although studies on rodents have proven the life-extending functions of GH, the results of them vary greatly. In one mice study, a prolonged life span of GH-receiving mice was observed, but the study was not conducted properly - the strain of mice was not long-lived anyway and the study was not run until the very end, so proper results can be observed. Contrasting, another rat study has shown absolutely no difference in disease patterns or maximum survival period between test rats and control rats. In conclusion, one might comment that HGH is very controversial and there is a great room for doubts about its effectiveness.

Below you find a list of scientific abstracts on HGH from pubmed.

In humans, both aging and GH deficiency are associated with reduced protein synthesis, decreased lean body and bone mass, and increased percent body fat. In healthy individuals, spontaneous and stimulated GH secretion, as well as circulating IGF-I and IGFBP-3 levels, are significantly decreased with advancing age. The extent to which these age-related changes in GH and IGF-I contribute to alterations in body composition and function remains to be elucidated. GH treatment of GH-deficient adults or old men with reduced IGF-I levels with exogenous GH increases plasma IGF-I, nitrogen retention, and lean body mass, decreases percent body fat, and exerts little effect on bone mineral density. Short-term adverse effects of GH therapy have been minimized by using low-dose regimens, but it is still uncertain whether long-term GH supplementation in adult life increases the risk of metabolic abnormalities or malignancy. Administration of GHRH, which has been shown to maintain the pattern of pulsatile GH secretion in old men, may represent another possible physiological approach to therapy. It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc. A great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life.

The influence of age on plasma growth hormone (HGH) and cortisol response to i.v. insulin (0.1 U/kg of body weight) was evaluated in 32 healthy subjects whose ages ranged between 20 and 84 years. A significant reduction in HGH response to insulin was observed with aging. In the young (20-34 years), middel-aged (35-49 years), and elderly (53-84 years) groups, average HGH peaks were 46.51 +/- 7.37, 29.95 +/- 5.35, and 14.31 +/- 2.39 ng/ml while average HGH areas were 2.911 +/- 0.484, 1.654 +/- 0.316, and 0.699 +/- 0.149 mug-min, respectively. Since insulin's hypoglycemic effect became less rapid with aging, this could, in part, explain the progressive decline in the HGH response to insulin. This phenomen may also be attributed to histological changes occurring in the pituitary with aging. Moreover, cortisol response was similar to all three age groups. These findings suggest that, while HGH response to insulin is correlated with age, adrenal response does not show any important modifications with aging.

GH replacement therapy in adults with adult-onset GH deficiency (GHD) has been shown to increase isometric and isokinetic muscle strength in a few trials with limited numbers of patients. In this single center, prospective, open-label study, the effects of 5-yr GH replacement therapy on muscle function were determined in 109 consecutive adults (61 men and 48 women) with adult-onset GHD. The mean initial GH dose was 0.88 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.46 mg/d. The mean IGF-I SD score increased from -1.54 at baseline to 1.53 at study end. A sustained increase in lean body mass and decrease in body fat was observed. The GH treatment induced persistent increases in isometric knee flexor strength, concentric knee flexor strength at an angular velocity of 60 degrees/sec, and right-hand peak grip strength. After correction for age and gender using observed/predicted value ratios, a sustained increase was also observed in isometric (60 degrees) and concentric (180 degrees/sec) knee extensor strength, average right-hand grip strength for 10 sec, and left-hand grip strength. At study end, knee flexor and extensor strength was 96-104% of predicted and hand grip strength was 84-90% of predicted values. The local muscle endurance was transiently decreased after correction for age and gender. No gender difference was found in the treatment responses in muscle strength. However, muscle strength (also after correction for age and gender) was lower in women than men throughout the study period. In conclusion, GH replacement therapy in adults with adult-onset GHD normalized isometric and isokinetic knee flexor and extensor strength. Hand grip strength increased but was not fully normalized.

Adults with GH deficiency (GHD) suffer from muscle weakness, which can be caused by the frequently reported decrease in muscle mass. However, measurements of both muscle strength and mass of muscle tested are scarce in adults with GHD. The aim of the present study was, therefore, to investigate intrinsic muscle strength (strength expressed per muscle volume unit) in adults with GHD at baseline and after 52 weeks of recombinant human GH (rhGH) therapy given in low, more physiological doses. A second objective was to investigate the influence of GH on muscle bioenergetics in the resting muscle. Isometric and isokinetic quadriceps strengths were measured in 28 males with GHD and in healthy controls matched for age and height. Quadriceps mass, determined by magnetic resonance imaging, and muscle bioenergetics, determined by phosphorus nuclear magnetic resonance spectroscopy, were measured in 20 of 28 patients with GHD and in controls matched for age and height. All patients were treated with doses of rhGH ranging from 0.6-1.8 IU/day, given for 52 weeks. Measurements of muscle mass, strength, and bioenergetics were repeated after 52 weeks of treatment with rhGH. The mean GH dose at 52 weeks of rhGH treatment was 1.3 +/- 0.8 IU/day. The mean serum insulin-like growth factor I level at baseline was 9.4 +/- 0.7 nmol/L and significantly increased to 26.4 +/- 1.2 nmol/L after 52 weeks of rhGH treatment. Adults with GHD had significantly reduced quadriceps muscle mass (P = 0.034) and reduced isometric muscle strength (P = 0.002) and tended to have low isokinetic muscle strength (P = 0.06), which all improved after rhGH therapy. Intrinsic muscle strength was not significantly different in adults with GHD compared with that in healthy controls and did not change during rhGH therapy. No bioenergetic abnormalities at baseline or after rhGH therapy were found in males with GHD. In conclusion, quadriceps muscle mass is decreased in adults with GHD and increased with rhGH therapy. These changes in muscle mass account for the changes in muscle strength found in these patients, as no changes in intrinsic muscle strength were found.

GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.

BACKGROUND. The declining activity of the growth hormone--insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. METHODS. To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed. During the treatment period, 12 men (group 1) received approximately 0.03 mg of biosynthetic human growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. Plasma IGF-I levels were measured monthly. At the end of each period we measured lean body mass, the mass of adipose tissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites. RESULTS. In group 1, the mean plasma IGF-I level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). There was no significant change in the bone density of the radius or proximal femur. In group 2 there was no significant change in lean body mass, the mass of adipose tissue, skin thickness, or bone density during treatment. CONCLUSIONS. Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.

This review examines the evidence that growth hormone has metabolic effects in adult human beings. The conclusion is that growth hormone does indeed have powerful effects on fat and carbohydrate metabolism, and in particular promotes the metabolic use of adipose tissue triacylglycerol. However, there is no proof that net protein retention is promoted in adults, except possibly of connective tissue. The overexaggeration of the effects of growth hormone in muscle building is effectively promoting its abuse and thereby encouraging athletes and elderly men to expose themselves to increased risk of disease for little benefit.

Growth hormone (GH) secretion in the elderly is generally diminished although there are marked individual differences ranging from normal GH secretion and normal levels of insulin-like growth factor (IGF)-I through low GH and subnormal IGF-I. It is assumed that the reduced central cholinergic activity leading to unrestrained somatostatin release leads to impaired GH secretion. The somatopause, if it occurs at all, is, in contrast to the menopause, a subtly developing physiological event. The menopause often causes severe symptoms that justify hormone replacement therapy, but the somatopause is a physiological event at the end of the lifespan with no acute symptoms that can be attributed to GH deficiency with certainty. Whether the non-specific symptoms of old age, i.e. truncal obesity, muscle atrophy, decreasing energy, and mental disorders, can be--even partially--blamed on decreased GH secretion is unclear. Thus, GH therapy in elderly patients, in the absence of pituitary disease cannot be recommended. In addition, the following has to be considered: 1) GH has to be given by subcutaneous injection, which may be technically difficult in elderly patients. 2) It is difficult to find the right individual dosage of GH since elderly patients may show increased sensitivity to GH therapy (compared with children) or may be GH-resistant. 3) Manifestation of diabetes mellitus may be enhanced in elderly patients. 4) The elevation of IGF-I levels may enhance the progression of malignant disease; it has been shown that the concentration of IGF-I in the circulation correlates to the frequency of prostatic cancer. Furthermore, acromegalic patients have a higher frequency of colonic polyps and gastrointestinal malignancies. 5) Even if problems such as dosage, mode of application and the questions of safety are resolved, the present costs of GH therapy will not allow to advocate GH treatment of all elderly patients with low levels of IGF-I. However, since some patients seem to benefit from GH therapy in senescence, further studies are needed. There may be a subset of elderly patients in whom GH treatment is useful. However, unless these patients are included in a study protocol, GH treatment should not be given to elderly patients in the absence of pituitary disease.

Human growth hormone is one of the hormones used most frequently in the setting of so-called anti-aging strategies. To date, the preventive value of such a hormone replacement therapy in relatively healthy and well functioning middle aged persons is unknown. Although growth hormone leads to significant alterations in body composition and changes in serum cholesterol levels in patients with adult growth hormone deficiency, there are currently no data supporting the hypothesis that growth-hormone in non deficient persons prolongs life span or reduces morbidity. Aging is associated with a reduction of GH-secretion, serum levels of insulin like growth factor I (IGF-I) and alterations in body composition and function. Based on the many clinical similarities between aging and acquired growth hormone deficiency, several studies have assessed the effects of growth hormone administration in healthy aged women and men. Only a few studies have addressed functional outcomes in a more frail population. These studies suggest that a defined group of older individuals with functional limitation might benefit from GH as a strategy to prevent further functional decline and delay nursing home admission. Because of the lack of proof in frail patients, uncertain long-term effects and high treatment costs GH-administration in the aged should currently be restricted to research questions. Future studies should address the question whether growth hormone alone or in combination with established strategies, such as exercise or improvement in nutrition will serve as a measure to prevent functional decline in frail geriatric patient populations.

BACKGROUND: Patients with adult-onset growth hormone deficiency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body composition have not been convincingly shown. OBJECTIVE: To determine whether long-term growth hormone therapy at a dose adjusted to maintain normal insulin-like growth factor 1 (IGF-1) levels has clinical effects in patients with adult-onset growth hormone deficiency. DESIGN: Randomized, placebo-controlled study. SETTING: Tertiary referral center. PATIENTS: 32 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone (initial daily dose, 10 micrograms/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if IGF-1 levels were elevated. MEASUREMENTS: Body composition and bone mineral density of the lumbar spine, femoral neck, and proximal radius were measured by dual energy x-ray absorptiometry at 6-month intervals. Markers of bone turnover were also measured during the first 12 months of the study. RESULTS: Growth hormone therapy increased bone mineral density in the lumbar spine by a mean (+/- SD) of 5.1% +/- 4.1% and bone mineral density in the femoral neck by 2.4% +/- 3.5%. In the growth hormone group, significant increases were seen in the following markers of bone turnover: osteocalcin (4.4 +/- 3.6 mg/L to 7.2 +/- 4.6 mg/L) and urinary pyridinoline (39.0 +/- 19.8 nmol/mmol of creatinine to 55.7 +/- 25.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 +/- 7.1 nmol/mmol of creatinine to 14.9 +/- 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31.9% +/- 6.5% to 28.3% +/- 7.0%), and lean body mass increased (from 59.0 +/- 8.5 kg to 61.5 +/- 6.9 kg). These changes were significant compared with corresponding changes in the placebo group (P < 0.01 for all comparisons). CONCLUSIONS: Growth hormone administered to men with adult-onset growth hormone deficiency at a dose adjusted according to serum IGF-1 levels increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects.

Growth hormone (GH) secretion declines during normal aging, resulting in lower serum insulin-like growth factor (IGF)-I levels. It has been proposed that many of the catabolic changes seen in normal aging, including osteoporosis and muscle atrophy, are in part caused by the decreased action of the GH-IGF-I axis. In addition, patients with GH deficiency have increased overall cardiovascular mortality. Several investigators have initiated GH treatment for elderly patients with relative hyposomatotropinemia. Initial reports suggest that GH can increase muscle mass, improve exercise tolerance, increase REM sleep and cause an enhanced sense of well-being. The basis for neuropsychiatric changes during GH therapy may be due to a direct CNS action of GH itself, to the increased IGF-I secretion which GH elicits, or to enhanced functioning of peripheral organ systems. Long-term studies will determine whether GH or IGF-I can exert a neurotrophic action in the aging brain.

Organic growth hormone (GH) deficiency in adults results in many adverse changes similar to the changes which occur in humans with increasing age. The secretion of GH from the anterior pituitary declines with increasing age. This observation, together with the changes in body composition associated with organic GH deficiency in adults, has led to the suggestion that the elderly without hypothalamic-pituitary disease are GH deficient and may benefit from GH therapy. The impact of organic disease of the hypothalamic-pituitary axis in the elderly may result in a reduction in GH secretion of up to 90%. This reduction in GH secretion is sufficient to cause a fall in the serum insulin-like growth factor-1 (IGF-1) concentration, abnormal body composition and abnormal bone turnover, although bone mineral density is unaffected. These changes are distinct from those associated with the hyposomatotropism of the elderly, but are less severe than those seen in younger adults with organic GH deficiency. In this chapter we discuss the effects of organic GH deficiency in elderly subjects and the potential effects of GH replacement therapy. We also examine the potential for GH therapy to correct some of the detrimental effects of the ageing process.

Aging is associated with a significant decline in secretion of growth hormone. This in turn leads to reduced circulating IGF-I and changes in IGF-binding proteins. Growth hormone replacement to growth hormone-deficient individuals has been shown to improve quality of life, enhance bone and muscle mass, and reduce cardiovascular risk. However, studies with growth hormone therapy in the elderly have been somewhat disappointing with minimal changes in lean body mass, musculoskeletal function, and overall quality of life. Moreover, recent evidence suggests that high normal serum IGF-I levels may be associated with a greater risk of several neoplastic disorders. Hence, there is less enthusiasm for reversing the changes of the "somatopause" with recombinant growth factors. An overview of these issues and the prospects for the future will be discussed in this article.

The aims of this review are to present a brief overview of growth hormone (GH) physiology and to summarize the studies of GH treatment in adults. Special attention has been paid to randomized controlled trials. Studies have revealed a partial deficiency of GH secretion in the elderly. GH secretion on the average declines by 14% with each decade in normal adults after 20 years of age. Aging has a central effect on the GH secretion and peripheric effect on insulin-like growth factor 1 (IGF-1) through changes in the body composition. GH administration may attenuate several important decrements in body composition and in function associated with aging. GH may also have very potent anabolic effects in surgical situations. Short-term side-effects of GH therapy include edema, carpal tunnel syndrome and arthralgia. A number of agents such as oral GH-releasing peptides (GHRPs) increase GH secretion; they may be an alternative to GH treatment in the future. Further studies of GH replacement are needed, examining issues such as dosage, tolerance and efficacy before the widespread use of GH in the elderly is advocated.

In aging, both changes in body composition and a decrease in GH secretion are observed. While recombinant human GH (rhGH) therapy was shown to be effective in GH-deficient adults, its effects on normal aging are controversial. This study addressed the effects of six-month administration of low dosages of rhGH in a group of 5 healthy elderly subjects (age range 71-86 years). All subjects received 2 IU rhGH (Saizen, Serono) x 2/week s.c., which was approximately 0.03 mg/kg/week, and were examined before and 1, 3, and 6 months after the start of the therapy, as well as 3 months after therapy was suspended. Hormonal, metabolic and biochemical parameters, as well as bone density at the forearm level, body composition and muscle strength, assessed by isokinetic exercises, were evaluated at each scheduled visit. After the start of the therapy, there was an average 9 +/- 3% increase (median 8%) in IGF-I levels (IGF-I basal: 145.6 +/- 9 ng/mL, IGF-I peak: 176.0 +/- 10; p < 0.001). An increase in lean body weight, a decrease in fat (p < 0.05), and an improvement in muscle strength (p < 0.01) were recorded. No significant variation was observed in the metabolic parameters. During rhGH therapy, an increase in both bone resorption and formation parameters, and a slightly decreasing trend in bone density were noted. In conclusion, low dosages of rhGH in healthy elderly subjects seem to determine some physiological effects, such as a slight increase in IGF-I levels, which in turn may be responsible for the positive effects on body mass composition and muscle strength, without producing side effects. On the other hand, 6-month subcutaneous rhGH therapy at the dosage employed was unable to improve bone density.

Detailed studies of the ontogeny of growth hormone (GH) secretion have shown unequivocally that GH is produced throughout life but secretion declines progressively to about 20% of that in puberty. These changes are accounted for in part by changes in central neuro-endocrine function, nutritional factors and by changes in sex steroid milieu. Mean 24-hour GH concentrations in the normal elderly are frequently below the limit of assay detectability where values are indistinguishable from matched adults with organic GH deficiency. The notion that diminished GH action may account for the undesirable changes in body composition and function in the elderly is supported by beneficial findings of GH treatment in GH-deficient adults. Preliminary results of GH treatment in the normal elderly suggest beneficial effects on body composition but a high incidence of side-effects. Questions addressing cost, benefit, dosage, safety and tolerance need to be critically addressed before GH can be considered for use in the aging.