Effects of Physiologic Growth Hormone Therapy on Bone Density and Body Composition in Patients with Adult-Onset Growth Hormone Deficiency Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. Physical Effects of Short-Term Recombinant Human Growth Hormone Administration in Abstinent Steroid Dependency Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men Short-term recombinant human growth hormone administration improves respiratory function in abstinent anabolic-androgenic steroid users. Body composition response to exogenous GH during training in highly conditioned adults. Recombinant human growth hormone in abstinent androgenic-anabolic steroid use: psychological, endocrine and trophic factor effects. Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion. Effect of exogenous growth hormone and exercise on lean mass and muscle function in children with burns. Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis. Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group. Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study.
Adults with hypopituitarism receive therapy that replaces cortisol , thyroid hormone , and gonadal steroids , but growth hormone replacement has typically been reserved for children with growth hormone deficiency . However , several observations suggest that growth hormone may have an important role in maintaining bone density and body composition in adults .  Bone density is reduced in patients with growth hormone deficiency that develops during childhood or adulthood [ 1 - 3 ] . In vitro , growth hormone binds to growth hormone receptors on rat osteoblast-like cells and produces a mitogenic response mediated by local synthesis and action of insulin-like growth factor 1 ( IGF-1 ) [ 4 , 5 ] . Administration of growth hormone to adults with growth hormone deficiency increases serum and urine markers of bone turnover [ 6 - 10 ] . In adults with childhood-onset growth hormone deficiency ( in whom osteopenia probably results from a failure to reach peak bone mass ) , growth hormone therapy increases bone density [ 3 , 8 , 10 , 11 ] . However , the effects of growth hormone replacement on bone density in adult-onset growth hormone deficiency are largely unknown . In addition to having an increased risk for fracture , adults with growth hormone deficiency have an excess risk for cardiovascular-related death that may be attributed to increased central fat mass [ 12 - 17 ] . Growth hormone therapy reduces body fat and increases lean mass in adults with growth hormone deficiency , primarily those in whom the deficiency developed during childhood [ 6 - 9 , 18 - 20 ] . However , previous studies of growth hormone replacement in adults have several important limitations . First , most of these studies used pharmacologic rather than physiologic doses of growth hormone . Second , most have focused on childhood-onset growth hormone deficiency . Third , effects of growth hormone on bone density in patients with adult-onset growth hormone deficiency have not been examined in a controlled study . Because of these limitations , the critical question of whether long-term growth hormone therapy is beneficial in patients with adult-onset growth hormone deficiency has not been definitively answered . We sought to determine whether long-term growth hormone replacement therapy , given at a dose adjusted according to IGF-1 levels , improves bone density , bone turnover , body composition , and several variables associated with quality of life in patients with adult-onset growth hormone deficiency . Methods Patients Thirty-two men ( median age , 51 years ; range , 24 to 62 years ) with a history of pituitary disease were recruited from the Massachusetts General Hospital Neuroendocrine Clinical Center and from surrounding communities . Growth hormone secretion profiles in 23 of these patients have been reported elsewhere [ 21 ] . All patients met the following inclusion criteria : 1 ) normal growth and development , 2 ) benign sellar neoplasm , pituitary apoplexy , or idiopathic hypopituitarism diagnosed after age 18 years , and 3 ) peak serum growth hormone levels less than 5 mg/L after receipt of two pharmacologic stimuli on separate mornings . The 13 patients younger than 50 years of age received intravenous insulin , 0.1 U/kg of body weight , and oral clonidine , 0.15 mg . The 18 patients 50 years of age or older received oral clonidine , 0.15 mg , and intravenous arginine , 30 g ; these patients were given arginine rather than insulin to avoid potential cardiovascular complications of hypoglycemia . Patients were excluded if they had a history of acromegaly or diabetes mellitus ; were taking drugs ( such as phenytoin or etidronate ) known to affect bone density ; were not receiving st and ard thyroid or adrenal hormone replacement therapy  if the patient was deficient in those hormones ; or had begun receiving adrenal , gonadal , or thyroid hormone replacement therapy within 6 months before study enrollment . Growth hormone deficiency was caused by a clinical ly nonfunctioning pituitary adenoma in 12 patients , prolactinoma in 9 patients , craniopharyngioma in 9 patients , pituitary apoplexy in 4 patients , Cushing disease in 1 patient , and adult-onset idiopathic hypopituitarism in 1 patient . Twenty-one patients were deficient in adrenocorticotropin , thyroid-stimulating hormone , and gonadotropins .  Five patients had two of these deficiencies , 5 patients had one , and 1 patient had none . Twenty-five patients were treated surgically ( 16 of the 25 were also treated with radiation or bromocriptine , or both ) . Five patients received bromocriptine with or without radiation therapy , and 2 were treated with hormonal replacement only . The Subcommittee on Human Studies of the Massachusetts General Hospital approved the study , and all patients gave written informed consent . Protocol Patients were r and omly assigned to receive recombinant human growth hormone ( Nutropin , Genentech , Inc. , South San Francisco , California ) at a daily dose of 10 g/kg subcutaneously or a placebo . The computerized r and omization , done by statisticians at Genentech , Inc. , stratified patients to assure balance between the groups with respect to age . Staff at Genentech , Inc. , informed the primary investigator of treatment assignment by telephone ; the study physician kept the information in a private computer data base . Only the study physician was aware of the treatment assignment . Patients were admitted to the General Clinical Research Center for measurements of bone mineral density of the lumbar spine , femoral neck , and proximal radius . Body mass index , lean body mass , and percentage of body fat were also measured . Patients had echocardiography and were tested for strength and exercise capacity . Urine was collected for 24 hours for measurement of pyridinoline , deoxypyridinoline , calcium , and creatinine excretion . Fasting blood sample s were drawn at 0900 hours for measurement of IGF-1 , glucose , insulin , lipids , and hemoglobin A1c values . Patients returned at 1 week , 1 month , and 3 months for outpatient measurement of serum IGF-1 , glucose , insulin , lipid ( at 1 and 3 months ) , and hemoglobin A1c ( at 3 months only ) values . Patients were readmitted at 6 , 12 , and 18 months so that the baseline evaluation could be repeated . Echocardiography and tests of strength and exercise capacity were repeated only at the 18-month visit . The growth hormone dose was reduced by 25 % if the patient 's serum IGF-1 level was found to be elevated at the 6- or 12-month visit ; serum IGF-1 levels were remeasured approximately 1 month after the dose was decreased . The dose was further adjusted if necessary . To maintain patient blinding , each placebo recipient was asked to reduce his dose by 25 % during the first 6 months of the study . Bone Density Bone mineral density of the lumbar spine , femoral neck , radius , and total body was determined by dual-energy x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . Density of the nondominant radius was measured at the junction of the proximal two thirds and the distal one third of the radial shaft ; the coefficient of variation for this measurement is 1.5 % [ 22 ] . The bone mineral density of the lumbar spine was assessed in the anteroposterior projection in all patients and in the lateral projection in the 22 patients whose body thickness did not exceed the manufacturer 's specified limit for the lateral measurement . Because lateral measurements of bone density in the spine eliminate the contribution of the posterior vertebral elements , they estimate trabecular bone mass better than do measurements made in the anteroposterior projection [ 23 ] . In 50 persons with paired measurements , the SDs for the anteroposterior and lateral measurements were 0.010 g/cm2 and 0.013 g/cm2 , respectively ; these values did not vary with bone density . The coefficient of variation for bone density at the femoral neck was 2.1 % in 51 persons with paired measurements [ 24 ] . All scans were review ed by one physician who did not know the patients ' treatment assignment . Follow-up scans were matched to baseline scans to ensure that identical bone regions were measured . Body Composition A research dietitian determined body mass index . Lean body mass and percentage of body fat were measured by dual-energy x-ray absorptiometry ( Hologic QDR-2000 ) . According to the manufacturer , the coefficient of variation is 1.0 % for lean mass and 1.5 % for percentage of body fat . This compares favorably with the coefficients of variation of other techniques for determining body composition , such as bioelectrical impedance ( 5 % ) , 40 K counting ( 3 % ) , and deuterium oxide dilation ( 3 % ) [ 25 ] . Biochemical Assays Serum IGF-1 levels were measured by radioimmunoassay after acid-alcohol extraction ( Nichols Institute , San Juan Capistrano , California ) . The ageadjusted normal ranges for this assay were 83.3 to 378.0 mg/L for men 20 to 40 years of age and 54.0 to 328.5 mg/L for men older than 40 years of age . Interassay coefficients of variation were 5.2 % at 121.5 mg/L and 15.2 % at 84.5 mg/L. Serum osteocalcin levels were measured by immunoradiometric assay ( SmithKline Beecham , Van Nuys , California ) . The intra-assay coefficients of variation were 11.5 % for low control serum pools ( 3 to 6 mg/L ) , 11.6 % for medium pools ( 6 to 10 mg/L ) , and 10.6 % for high pools ( 25 to 35 mg/L ) . Urinary excretion of total pyridinoline and deoxypyridinoline was measured using high-performance liquid chromatography ( SmithKline Beecham ) . The intra-assay coefficients of variation for measurement of pyridinoline levels were 9.5 % at 13.8 nmol/mmol of creatinine , 9.6 % at 37.0 nmol/mmol of creatinine , and 10.7 % at 47.5 nmol/mmol of creatinine . The intra-assay coefficients of variation for measurement of deoxypyridinoline excretion were 15.8 % at 3.2 nmol/mmol of creatinine , 13.5 % at 6.7 nmol/mmol of creatinine , and 9.8 % at 10.7 nmol/mmol of creatinine . Other assays were done at the Massachusetts General Hospital as described elsewhere [ 26 ] . Echocardiography Transthoracic two-dimensional echocardiography was done while patients were in the left lateral decubitus Aging is associated with alterations in body composition and a decline in functional status . Healthy older persons have decreased muscle mass , increased fat mass , and decreased strength [ 1 - 3 ] . The muscle strength of 70-year-old men is about half that of young adults [ 3 ] . The risk for falls , fractures , and frailty increases with age-related decreases in muscle strength [ 4 - 6 ] . Pituitary secretion of growth hormone and circulating levels of insulin-like growth factor 1 decrease with aging [ 7 ] ; these events are called somatopause . Growth hormone is both anabolic and lipolytic [ 8 - 10 ] , and the action of growth hormone on peripheral tissues is mediated , in part , by circulating insulin-like growth factor 1 [ 11 ] . Growth hormone deficiency results in body composition changes that are similar to the changes seen with aging [ 1 , 7 ] . Growth hormone replacement in patients with hypopituitarism and in older men reverses some of the body composition changes associated with both growth hormone deficiency and aging [ 12 - 14 ] . In a study by Rudman and colleagues [ 14 ] on the effects of growth hormone replacement therapy on body composition , the administration of growth hormone to 12 men 61 to 73 years of age for 6 months increased lean body mass by 9 % and decreased adipose tissue mass by 15 % ( P < 0.005 ) . Circulating insulin-like growth factor 1 levels increase similarly in young and old men after exogenous administration of either growth hormone or growth hormone-releasing hormone [ 7 , 11 ] . Therefore , low insulin-like growth factor 1 levels reflect decreased growth hormone secretion rather than a loss of hepatic responsiveness to the hormone . On the basis of these data , it has been proposed that diminished secretion of growth hormone is responsible , in part , for the somatic changes of aging [ 14 ] . Growth hormone replacement has been shown to improve muscle volume , isometric strength , and exercise capacity in young adults with hypopituitarism [ 12 , 13 ] . In one study of growth hormone-deficient young adults treated with growth hormone [ 12 ] , thigh muscle volume increased by 6 % ( P < 0.01 ) , and isometric strength increased by 8 % ( P = 0.08 ) compared with controls . Increases in isometric strength were associated with increases in muscle volume ( r = 0.75 ; P < 0.001 ) . Exercise capacity also increased by 12 % ( P < 0.05 ) . Such data on the effects of growth hormone replacement therapy on strength or function are not available for older persons . To test the hypothesis that the muscle weakness and functional decline associated with aging are in part due to decreased growth hormone secretion , we conducted a 6-month r and omized , controlled , double-blind trial comparing recombinant human growth hormone therapy with placebo in 56 elderly men whose baseline insulin-like growth factor 1 levels were less than the tenth percentile found in younger healthy adults . Methods Participants We recruited healthy , ambulatory , community-dwelling men older than 69 years of age . Because growth hormone secretion is pulsatile and diurnal , a more convenient measure of growth hormone secretion is insulin-like growth factor 1 , which has constant and nonpulsatile plasma levels [ 1 , 7 , 15 , 16 ] . Inclusion criteria included two fasting morning plasma insulin-like growth factor 1 levels ( assayed after plasma was extracted with acid ethanol by the Nichols Institute [ 17 ] ) less than 161 ng/mL that were obtained at least 2 weeks apart , a fasting blood glucose level less than 8.4 mmol/L ( 140 mg/dL ) , stable body weight between 80 % and 120 % of ideal body weight [ 18 ] during the previous year , and a normal complete blood count at baseline . Participants had to be able to follow the study instructions and perform the strength measurements . Exclusion criteria included diseases that might contraindicate the use of growth hormone ( such as carcinoma within the previous 5 years , diabetes mellitus , and the carpal tunnel syndrome ) , uncontrolled hypertension ( blood pressure more than 180/100 mm Hg ) , oral corticosteroid use within the previous year , or a recent change in ambulatory status ( for example , as the result of a stroke ) . Design After the participants gave informed written consent , the following baseline measurements were obtained : question naires ( demographic characteristics and medical conditions ) ; fasting blood chemistry ( levels of electrolytes , urea nitrogen , creatinine , glucose , calcium , phosphate , and albumin ) ; complete blood count ; serum and rogen levels ( total and free testosterone and dehydroepi and rosterone ) ; fasting lipoprotein levels ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and triglycerides ) and thyroid-stimulating hormone and free thyroxine levels ; 24-hour urinary calcium excretion ; and creatinine clearance . At baseline , we also measured the body composition , strength , and functional ability of all participants . We then used a computer-generated r and omization table to assign each participant to receive either growth hormone or placebo . Participants , investigators who had contact with the participants , and laboratory personnel were blinded to treatment status . Treatment consisted of recombinant human growth hormone ( somatropin [ Nutropin , Genentech ] ) , 0.03 mg/kg of body weight , or an equivalent placebo volume ( supplied in identical vials by Genentech ) injected subcutaneously three times per week in the morning for 6 months . We evaluated the participants after 2 , 4 , 8 , 12 , 18 , and 24 weeks of treatment to determine whether side effects developed and to ensure compliance . Participants were examined and specifically asked about the presence of the following side effects : malaise , fatigue , edema , arthralgias , arthritis , the carpal tunnel syndrome , muscle discomfort , dyspnea , depression , polydipsia , polyuria , nocturia , and tender or enlarged breasts . At each visit , we measured fasting morning plasma insulin-like growth factor 1 levels 48 hours after the last treatment dose and repeated most of the baseline blood and urinary tests . We adjusted the dose of recombinant human growth hormone to maintain serum insulin-like growth factor 1 levels between 190 and 350 ng/mL ( the 25th to 75th percentiles of a young adult population ) 48 hours after a dose . To preserve blinding , each growth hormone recipient was paired with a placebo recipient . An unblinded physician who had not had contact with the participants review ed insulin-like growth factor 1 levels during the trial . If the levels were less than 190 ng/mL or greater than 350 ng/mL , the unblinded physician instructed study personnel to make identical dose adjustments for both participants in the pair . The dose was also decreased in any participant who reported troublesome side effects that were potentially attributable to growth hormone . We repeated all study outcome measurements after 6 months of treatment . We also measured fasting plasma renin activity , cortisol and aldosterone levels , and 24-hour urine aldosterone excretion . The investigational review boards of the University of California , San Francisco , and the Department of Veterans Affairs Medical Center , San Francisco , approved the study protocol . Measurements Body Composition We used dual-energy x-ray absorptiometry ( Lunar DPX-Plus , Madison , Wisconsin ) total-body composition scans to measure lean tissue mass and fat mass , and we used anterior-posterior lumbar scans to measure bone mineral content . We measured skin thickness using ultrasonography with a 10-MHz transducer ( Diasonics , Milpitas , California ) that was positioned transversely 5 cm below the umbilicus . Using the same transducer , we made two ultrasonographic measurements on each participant . The average of the two measurements was used for analysis . The study radiologist , who was blinded to the participants ' treatment status , interpreted all test results . Muscle Strength The study 's physical therapist measured the muscle strength of the participants ' knee flexor and extensor muscles using an isokinetic dynamometer ( Cybex 340 , Lumex , Bay Shore , New York ) . Using a st and ard protocol , we measured peak torque of knee flexion and extension at joint speeds of 90 , 120 , and 180 degrees per second . We measured h and grip strength according to a st and ardized protocol using a grip dynamometer ( Smedley Grip Dynamometer , JA Preston , Jackson , Mississippi ) . The greater of the two measurements was used for analysis . Systemic Endurance To assess systemic endurance , we measured maximal oxygen consumption ( Vo 2 max ) during exercise cycle testing . Upright exercise testing was done using an electronically braked cycle ergometer ( Erich Jaeger , Rockford , Illinois ) . Exercise was initially done unloaded and was then increased by 25 watts every 2 minutes . Participants continued to exercise until they were exhausted or unable to maintain critical pedal frequency ( greater than 50 revolutions per minute ) . During exercise cycle testing , we continuously measured respiratory gas exchange to determine Vo 2 max ( Ergopneumotest , Erich Jaeger ) . Physical Performance The study 's physical therapist used the Physical Performance Test [ 19 ] to assess the participants ' performance on nine physical functions . Participants were asked to write a prescribed sentence , transfer kidney beans using a teaspoon , place a heavy book on a shelf , remove a jacket , pick up a penny from the floor , turn 360 degrees , walk a 50-foot walking test course , and climb stairs to determine speed and the number of flights climbed before the development of fatigue . The test score is based on the time required to complete each task . Higher scores ( the best performance is a maximum score of 36 ) are associated with the shortest time required to complete a task and with better functional status . Cognitive Function and Mood Each participant completed the Trails B Test , the Mini-Mental State Examination , the Digit Symbol Substitution Test , and the Geriatric Depression Scale [ 20 - 23 ] . The Trails B Test ( from the Halstead-Reitan Neuropsychological Test 1 . In adult humans with growth hormone deficiency , treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance . The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone ( 0.07 units/kg at night ) in a double-blind , placebo-controlled trial lasting 6 months . 2 . Compared with placebo , resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone . No differences were noted between the groups with respect to left ventricular end-systolic dimension , fractional shortening , wall thicknesses or mean arterial blood pressure . Left ventricular myocardial mass increased in the group given recombinant human growth hormone . 3 . The supine plasma renin activity was increased and remained elevated over the 6 months , whereas the plasma aldosterone concentration was unchanged , after treatment with recombinant human growth hormone . Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone . 4 . We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency result ed in small increases in left ventricular pre-load , due to the sodium-retaining action of growth hormone . Activation of the renin-aldosterone system was involved in such changes . Myocardial hypertrophy was observed without changes in mean arterial pressure , reflecting the anabolic action of growth hormone Background / Aims : Recombinant human growth hormone ( rhGH ) as opposed to cadaver pituitary GH is misused for physical improvement . Six days ’ rhGH administration , in abstinent anabolic- and rogenic steroid dependents , was compared with controls . Method : Male subjects ( n = 48 ) were r and omly divided into two groups : ( 1 ) : control group ( C ) , n = 24 , mean ± SD , age 32 ± 11 years , height 1.8 ± 0.06 m ; ( 2 ) :  rhGH-using group  ( 0.058 IU·kg–1·day–1 ) ( GH ) , n = 24 , mean ± SD , age 32 ± 9 years , height 1.8 ± 0.07 m. Physiological measurements included anthropometry , strength , power and peak oxygen uptake ( VO2 peak ) . Biochemical measurements included haemoglobin , packed cell volume , glucose , sodium , potassium , urea , creatinine , total protein , albumin , thyroid function , testosterone , prolactin , cortisol , GH and insulin-like growth factor-I ( IGF-I ) . Results : Strength , peak power output and IGF-I significantly increased and total protein , albumin and free tetra-iodothyronine significantly decreased compared to controls ( p < 0.05 ) and within the GH group ( p < 0.017 ) . Fat-free mass index and VO2 peak significantly increased , while body fat and thyroid-stimulating hormone significantly decreased within the GH group ( p < 0.017 ) . Conclusions : Short-term rhGH  increased strength and power . Of therapeutic value is the possibility that muscle bulk and strength could be increased in patients with muscle-wasting conditions The effect of recombinant GH on strength , body composition and endocrine parameters in power athletes was investigated in a controlled study . Twenty-two healthy , non-obese males ( age 23.4 + /- 0.5 years ; ideal body weight 122 + /- 3.1 % , body fat 10.1 + /- 1.0 % ; mean + /- SEM ) were included . Prob and s were assigned in a double-blind manner to either GH treatment ( 0.09U ( kg BW)-1 day-1 sc ) or placebo for a period of six weeks . To exclude concurrent treatment with and rogenic-anabolic steroids urine specimens were tested at regular intervals for these substances . Serum was assayed for GH , IGF-I , IGF-binding proteins , insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter . Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus . Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper . For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed . GH , IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group . Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated prob and s. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles . Body weight and body fat were not changed significantly during treatment . We conclude that the anabolic , lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To determine whether six days recombinant human growth hormone ( rhGH ) in an abstinent anabolic- and rogenic steroid ( AAS ) group had any cardiovascular and biochemical effects compared with a control group . METHODS Male subjects ( n=48 ) were r and omly divided , using a single blind procedure into two groups : ( 1 )  control group ( C ) n=24 , mean+/-SD , age 32+/-11 years ; height 1.8+/-0.06 m ; ( 2 ) rhGH using group ( 0.058IUkg(-1)day(-1 ) ) ( GH ) n=24 , mean+/-SD , age 32+/-9 years ; height 1.8+/-0.07 m . Physiological responses , anthropometry , arterial pulse wave velocity ( APWV ) , blood pressure ( BP ) , heart rate ( HR ) , peak oxygen uptake ( VO(2 ) peak ) and biochemical indices were investigated . RESULTS Body mass index , fat-free mass index and VO(2 ) peak significantly increased while body fat significantly decreased within GH ( all P<0.017 ) . Insulin like growth factor-I significantly increased within GH ( P<0.017 ) and compared with C ( P<0.05 ) . Serum sodium significantly increased ( P<0.017 ) and serum homocysteine , high sensitivity C-reactive protein , thyroid stimulating hormone and tetra-iodothyronine ( T(4 ) ) , significantly decreased within GH ( all P<0.017 ) . T(4 ) significantly decreased compared with C ( P<0.05 ) . Arterial pulse wave velocity , peak and recovery systolic and diastolic BP , significantly decreased compared with C ( P<0.05 ) . Resting HR and rate pressure product ( RPP ) significantly increased compared with C ( P<0.05 ) . CONCLUSION The findings of this study suggest that short term use of rhGH may have beneficial effects on endothelial function and specific inflammatory markers of cardiovascular disease in abstinent AAS users , but may have an adverse effect on the cardiovascular system , as evidence d by the increase in resting RPP Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population OBJECTIVES To determine whether 6 days recombinant human growth hormone ( rhGH ) administration , in an abstinent anabolic- and rogenic steroid ( AAS ) using group had any respiratory , endurance exercise and biochemical effects compared with an abstinent AAS control group . METHODS Male subjects ( n=48 ) were r and omly divided , using a single blind procedure into two groups : ( 1 )  control group ( C ) n=24 , means+/-SD , age 32+/-11 years ; height 1.8+/-0.06 m ; ( 2 ) rhGH using group ( 0.019 mg kg(-1 ) day(-1 ) ) ( GH ) n=24 , means+/-SD , age 32+/-9 years ; height 1.8+/-0.07 m.  Anthropometry , respiratory muscle function and endurance exercise were investigated . Respiratory measurements examined , were forced expiratory volume in one second , forced vital capacity , maximum inspiratory pressure and maximum expiratory pressure . Endurance exercise was assessed by measuring peak oxygen uptake ( VO(2)peak ) . Biochemical analysis included ; haemoglobin , packed cell volume , glucose , sodium , urea , creatinine , total protein , albumin , testosterone and insulin like growth factor-I ( IGF-I ) . RESULTS Forced expiratory volume in one second/forced vital capacity , maximum inspiratory pressure , maximum expiratory pressure , and IGF-I significantly increased compared with the control group ( all P<0.05 ) . Body mass index , fat free mass index , peak oxygen uptake , maximum inspiratory pressure , maximum expiratory pressure , IGF-I and serum sodium significantly increased , whilst body fat , total protein and albumin , significantly decreased within the GH group ( all P<0.017 ) . CONCLUSION The findings of this study indicated that short-term high dose rhGH increased aerobic performance and respiratory muscle strength in former AAS users The effects of biosynthetic methionyl-human growth hormone ( met-hGH ) on body composition and endogenous secretion of growth hormone ( GH ) and insulin-like growth factor I ( IGF-I ) were studied in eight well-trained exercising adults between 22 and 33 yr of age . By the use of double-blind procedures , met-hGH ( 2.67 mg/0.5 ml diluent , 3 days/wk ) and bacteriostatic water ( placebo , 0.5 ml , 3 days/wk ) were administered in a repeated- measures design that counterbalanced treatment order . Duration of each treatment was 6 wk . Subjects trained with progressive resistance exercise throughout and were maintained on a high-protein diet monitored by extensive compositional analyses of daily dietary intake records . Hydrodensitometry revealed that met-hGH significantly decreased percent body fat ( % fat ) and increased fat-free weight ( FFW ) and FFW/fat weight ( FW ) , whereas the placebo treatment did not change any of these measures . Changes in FFW/FW correlated with the relative dose of met-hGH but did not correlate with either the peak GH response to L-dopa/arginine stimulation or IGF-I levels obtained after treatment with placebo . There were no differences between treatments in the dietary intakes of total kilocalories , protein , carbohydrates , and fat . Mean IGF-I levels were elevated after treatment with met-hGH compared with postplacebo levels . After treatment with met-hGH , five of seven subjects had a suppressed GH response to stimulation from either L-dopa/arginine or submaximal exercise . We conclude that supraphysiological doses of met-hGH will alter body composition in exercising adults in a relative dose-dependent manner and that such treatment may suppress endogenous release of GH in some individuals This study examined whether six days recombinant human growth hormone ( rhGH ) affected psychological profile in an abstinent and rogenic-anabolic steroid ( AAS ) abusing group , compared with an abstinent AAS control group . Male subjects ( n = 48 ) were assigned in a r and om fashion into one of two groups : ( 1 ) : ( n=24 ) control group ( C ) ; ( 2 ) : ( n=24 ) rhGH group ( GH ) . A hospital anxiety scale ( HADS ) question naire was completed by all subjects . Physiological responses investigated included anthropometry . Biochemical markers examined included ; serum glucose , sodium , urea , lipid profile , high sensitivity C-reactive protein ( hsCRP ) , homocysteine ( HCY ) , tetra-iodothyronine ( T4 ) , thyroid stimulating ( TSH ) , luteinising ( LH ) and follicle stimulating ( FSH ) hormones , testosterone ( T ) , prolactin ( PRL ) , cortisol and insulin like growth factor-1 ( IGF-I ) . HADS question naire significantly decreased in both anxiety ( A ) and depression ( D ) symptoms within GH ( P<0.017 ) and compared with C ( P<0.05 ) . Body mass index ( BMI ) and fat-free mass index ( FFMI ) significantly increased ( both P<0.017 ) while body fat significantly decreased within GH ( P<0.017 ) . IGF-I significantly increased within GH ( P<0.017 ) and significantly increased compared with C ( P<0.05 ) . Serum sodium significantly increased ( P<0.017 ) and serum HCY , hsCRP , TSH and T4 , significantly decreased within GH ( all P<0.017 ) . PRL significantly increased and T4 significantly decreased compared with C ( both P<0.05 ) . The findings of this study suggest that short term use of rhGH has beneficial effects on mental state  in individuals who were previous abusers of AAS and appeared to have a beneficial effect on cardiovascular risk markers associated with adverse mental health Using double-blind , placebo-controlled procedures , the effects of methionyl-human growth hormone ( met-hGH ) on the tumor cytotoxic activity of natural killer ( NK ) cells were studied in seven healthy adults using a repeated measures experiment . Subjects were assigned at r and om to either a placebo ( bacteriostatic water ) treatment condition or a met-hGH ( 16.0 mg/wk of Protropin ) treatment condition , then crossed-over to the alternative treatment . Treatments were delivered on alternate days ( 3 d/wk ) for 6 weeks . Without bias from the met-hGH treatment , there was no evidence for GH hyposecretion as measured by the peak circulating GH response to exercise stimulation ( 14.1 + /- 3.1 ng/mL ) or insulin-like growth factor ( IGF-I ) levels ( 0.82 + /- 0.09 U/mL ) . When compared with placebo , met-hGH induced a significant overall increase in the percent specific lysis ( % SL ) of K562 tumor target cells ( placebo 22.2 + /- 1.7 v met-hGH 28.5 + /- 2.1 % SL ; P = .008 ) . NK activity was increased within the first week of treatment and this level was maintained throughout the remaining period of supplementation . There was a trend ( P = .057 ) for the met-hGH-induced percent change in NK activity ( NK% ) to be inversely related to placebo IGF-I levels ( r = -.761 ) , while there were significant positive correlations between NK% and the met-hGH-induced percent changes in IGF-I ( r = .727 ; P = .035 ) , the fat-free mass (FFM)/fat mass ( FM ) ratio derived by hydrodensitometry ( r = .792 ; P = .012 ) , and the endogenous GH response to exercise ( r = .469 ; P = .034 ) . ( ABSTRACT TRUNCATED AT 250 WORDS We tested the hypothesis that the administration of recombinant human growth hormone ( rHGH ) and exercise would increase lean body mass ( LBM ) and muscle strength in burned children to a greater extent than rHGH or exercise separately . Children , ages 7 - 17 yr , with > 40 % body surface area burned , were r and omized into groups . One group ( GHEX , n = 10 ) participated in a 12-wk in-hospital physical rehabilitation program supplemented with an exercise program and received 0.05 mg . kg(-1 ) . day(-1 ) of rHGH . A second exercising group ( SALEX , n = 13 ) received saline . A third group ( GH , n = 10 ) received a similar dose of rHGH as GHEX and participated in a 12-wk , home-based physical rehabilitation program without exercise . The fourth group ( Saline , n = 11 ) received saline and participated in a 12-wk , home-based physical rehabilitation program without exercise . The mean ( + /-SE ) percent change in lean body mass after 12 wk was not significantly different between GHEX ( 9.0 + /- 2.1 % ) , SALEX ( 5.4 + /- 1.6 % ) , and GH ( 5.8 + /- 1.8 % ) groups ( P = 0.33 ) . However , the mean percent change in muscle strength was significantly greater in the GHEX ( 36.2 + /- 5.4 % ) and SALEX ( 42.6 + /- 10.0 % ) groups than in the GH ( -7.4 + /- 4.7 % ) or Saline ( 6.7 + /- 4.4 % ) groups ( P = 0.008 ) . In summary , rHGH GHEX , SALEX , and GH alone produced similar improvements in LBM . However , muscle strength was only increased via exercise CONTEXT Despite the fact that the use of GH as a doping agent in sports is widespread , little is known about its short-term effects . OBJECTIVE The objective was to study the effects of GH  on exercise capacity . DESIGN A double-blind , placebo-controlled study was used , with a treatment period of 28 d. SETTING Subjects from general community studied ambulatory at a university hospital . PARTICIPANTS Thirty healthy active young normal volunteers ( 15 women and 15 men ) were recruited by local announcement , and all completed the study . INTERVENTION All subjects were r and omized to receive a low GH dose ( 0.033 mg/kg.d or 0.1 IU/kg.d ) , a high GH dose ( 0.067 mg/kg.d or 0.2 IU/kg.d ) , or placebo . MAIN OUTCOME MEASURES Power output and oxygen uptake on bicycle exercise were the main outcome measures . RESULTS We found no effect of the low or high dosages of GH on maximum oxygen uptake during exercise ( mean + /- se for placebo , 45.2 + /- 1.6 to 45.2 + /- 2.1 ml/kg.min ; GH low dose , 42.8 + /- 1.6 to 42.8 + /- 1.6 ml/kg.min ; GH high dose , 44.8 + /- 3.4 to 44.8 + /- 2.2 ml/kg.min ; not significant by two-way ANOVA ) . Neither was there any effect on maximum achieved power output during exercise or on blood pressure , heart rate , or the electrocardiographic ST level at rest or during exercise . GH significantly increased total body weight ( P = 0.028 ) , an effect predominantly ascribed to fluid retention ( increased extracellular water volume ) , whereas muscle mass ( as indicated by intracellular water volume ) did not change . However , changes in the latter correlated to changes in physical performance , possibly due to different training efforts . CONCLUSION Administration of supraphysiological recombinant human GH during a period of 4 wk does not improve power output or oxygen uptake OBJECTIVE To evaluate the effect of severe head injury on both the secretion of basal pituitary hormones and the response to exogenous synthetic hypothalamic releasing factors administration . DESIGN Prospect i ve , clinical study . SETTING General intensive care unit in a university teaching hospital , Italy . PATIENTS Comatose , head-injured patients ( n = 22 ) , all intubated and mechanically ventilated , invasively monitored without previous endocrinologic problems and substitutive therapies . INTERVENTIONS Routine neuroemergency procedures ; administration of exogenous , synthetic hypothalamic releasing hormones . MEASUREMENTS AND MAIN RESULTS Determinations of basal concentrations of growth hormone ( GH ) , prolactin ( PRL ) , thyroid-stimulating hormone ( TSH ) , triiodothyronine , and thyroxine were performed daily in the first week and on days 15 and 16 after the trauma . Plasma insulin-like growth factor-I and cortisol were also determined on days 2 , 7 , and 15 . We carried out a thyrotropin-releasing hormone ( TRH ) test for the evaluation of the PRL , TSH , and GH responses on days 1 and 16 after the trauma and a growth hormone-releasing hormone ( GHRH ) test for the evaluation of GH and PRL responses on days 2 , 7 , and 15 after the trauma . Outcome was evaluated at 6 mos with the GOS . Triiodothyronine showed low values , even if in the normal range ; thyroxine remained in the normal range . Significant increases in insulin-like growth factor-I concentrations were observed on both days 7 and 15 compared with day 2 ( p = .024 and p = .034 , respectively ) . The GH response to GHRH was significantly greater on days 7 and 15 than in the very acute phase ( p < .01 comparing days 7 and 15 vs. day 2 ) . We found a higher GH response to GHRH on day 7 in group 1 vs. group 2 ( as both peak and area under the curve , p = .018 and p = .015 , respectively ) . No difference in GH response was detected on days 2 and 15 . A " paradoxical " response of GH to TRH was observed on the day after the head trauma ( basal vs. peak , p = .002 ) but not on day 16 . The GH peak response to TRH was greater on day 1 in those patients with an unfavorable course ( group 1 vs. group 2 , p < .05 ) . The TSH response to TRH was not significantly correlated to the severity of trauma , but it was significantly ( p < .04 ) higher in group 1 than in group 2 . Finally , a " paradoxical " PRL response to GHRH administration was present on day 2 ( basal vs. peak , p=.0003 ) , day 7 ( basal vs. peak , p = .01 ) , and on day 15 after the trauma ( basal vs. peak , p = .04 ) . CONCLUSIONS Some of the responses to provocative tests have been identified as " paradoxical " and seem to have a great importance in the definition of prognosis in severe head-injured patients , specifically the GH response to TRH and the PRL response to GHRH  that are significantly correlated with outcome GH is being used by elite athletes to enhance sporting performance . To examine the hypothesis that exogenous 22-kDa recombinant human GH ( rhGH ) administration could be detected through suppression of non-22-kDa isoforms of GH , we studied seventeen aerobically trained males ( age , 26.9 + /- 1.5 yr ) r and omized to rhGH or placebo treatment ( 0.15 IU/kg/day for 1 week ) . Subjects were studied at rest and in response to exercise ( cycle-ergometry at 65 % of maximal work capacity for 20 min ) . Serum was assayed for total GH ( Pharmacia IRMA and pituitary GH ) , 22-kDa GH ( 2 different 2-site monoclonal immunoassays ) , non-22-kDa GH ( 22-kDa GH-exclusion assay ) , 20-kDa GH , and immunofunctional GH . In the study , 3 h after the last dose of rhGH , total and 22-kDa GH concentrations were elevated , reflecting exogenous 22-kDa GH . Non-22-kDa and 20-kDa GH levels were suppressed . Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups . In identical exercise studies repeated between 24 and 96 h after cessation of treatment , the magnitude of the responses of all GH isoforms was suppressed ( P < 0.01 ) , but the relative proportions were similar to those before treatment . We conclude : 1 ) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days ; 2 ) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations ; and 3 ) these methods may prove useful in detecting rhGH abuse in athletes The effects of GH on bone remodeling in healthy adults have not been systematic ally investigated . An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports . The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers . Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter , r and omized , double blind , placebo-controlled study and assigned to receive either placebo ( 40 subjects ) or recombinant human GH ( 0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects ) . The treatment duration was 28 days , followed by a 56-day wash-out period . The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen , the resorption marker type I collagen telopeptide , and the soft tissue marker procollagen type III . All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline ( P < 0.01 ) and placebo ( P < 0.01 ) groups . The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III ( from 0.53 + /- 0.13 to 0.61 + /- 0.14 kU/L ; P < 0.02 ) and osteocalcin ( from 12.2 + 2.9 to 14.6 + /- 3.6 UG/L ; P < 0.02 ) , whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 ( from 3.9 + /- 1.2 to 5.1 + /-1.5 microg/L and from 174 + /- 60 to 173 + /- 53 microg/L , respectively ) . Gender-related differences were observed in the study ; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide ( P < 0.001 ) . In conclusion , exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner . As GH-induced modifications of most markers , in particular procollagen type III and osteocalcin , persist after GH withdrawal , they may be suitable markers for detecting GH abuse Patients with chronic obstructive pulmonary disease ( COPD ) often develop weight loss , which is associated with increased mortality . Recombinant human growth hormone ( rhGH ) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients . The aim of this study was to assess the effects of rhGH administration on the nutritional status , resting metabolism , muscle strength , exercise tolerance , dyspnea , and subjective well-being of underweight patients with stable COPD . Sixteen patients attending a pulmonary rehabilitation program ( age : 66 + /- 9 yr ; weight : 77 + /- 7 % of ideal body weight ; FEV1 : 39 + /- 13 % of predicted ) were r and omly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion . Measurements were made at the beginning ( DO ) and at the end ( D21 ) of treatment and 2 mo later ( D81 ) . Body weight was similar in the two groups during the study , but lean body mass was significantly higher in the rhGH group at D21 ( p < 0.01 ) and D81 ( p < 0.05 ) . The increase in lean body mass was 2.3 + /- 1.6 kg in the rhGH group and 1.1 + /- 0.9 kg in the control group at D21 and 1.9 + /- 1.6 kg in the rhGH group and 0.7 + /- 2.1 kg in the control group at D81 . At D21 , the resting energy expenditure was increased in the rhGH group ( 107.8 % of DO , p < 0.001 compared with the control group ) . At D21 and D81 , the changes in maximal respiratory pressures , h and grip strength , maximal exercise capacity , and subjective well-being were similar in the two groups . At D21 , the 6-min walking distance decreased in the rhGH group ( -13 + /- 31 % ) and increased in the control group ( + 10 + /- 14 % ; p < 0.01 ) . We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD
Some have suggested that growth hormone is a wonder drug ( 16 ) that results in ripped muscle ( 17 ) and provides stamina-increasing properties ( 18 ) .
The use of human growth hormone to improve athletic performance has recently received worldwide attention .
This practice , often called sports doping , is banned by most professional sports leagues and associations , including the International Olympic Committee , Major League Baseball , and the National Football League ( 13 ) .
However , a wide range of athletes , including those from baseball ( 46 ) , cycling ( 7 , 8) , and track and field ( 5 , 9 ) , have been implicated in or have confessed to illicit growth hormone use .
The Mitchell report ( 10 ) recently identified 89 Major League Baseball players who allegedly used performance-enhancing drugs , and some of these players have subsequently admitted to using growth hormone ( 11 , 12 ) .
Part of the attraction of using growth hormone as a performance enhancer has been that its use is difficult to detect .
The World Anti-Doping Agency , whose formation stemmed from the widely publicized doping sc and al of the 1998 Tour de France ( 13 ) , first used a blood test to detect exogenous growth hormone during the 2004 Olympic Games in Athens .
Although growth hormone is reportedly used to enhance athletic performance and has been called the most anabolic substance known ( 15 ) , its efficacy for this purpose is not well established .
Exogenous growth hormone therapy in growth hormonedeficient adults ( that is , those with growth hormone deficiency due to hypothalamic or pituitary defects ) results in increased lean mass and decreased fat mass ( 19 ) , and comparable body composition changes are seen in healthy elderly adults who receive growth hormone ( 20 ) .
Some experts , however , have suggested that the strength-enhancing properties of growth hormone among healthy adults have been exaggerated ( 15 ) .
Serious side effects , including diabetes , hepatitis , and acute renal failure , may occur in athletes using high-dose growth hormone ( 21 ) .
Furthermore , the use of growth hormone for athletic enhancement is not approved by the U.S. Food and Drug Administration , and the distribution of growth hormone for this purpose is illegal in the United States ( 22 ) .
We performed a systematic review of r and omized , controlled trials to determine the effects of growth hormone therapy on athletic performance in healthy , physically fit , young adults .
Our primary aim was to evaluate the effects of growth hormone on body composition , strength , basal metabolism , and exercise capacity .
In addition , we sought to synthesize the evidence on adverse events associated with growth hormone in the healthy young and assess the quality of the published literature .