title: Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men. Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. Effects of Physiologic Growth Hormone Therapy on Bone Density and Body Composition in Patients with Adult-Onset Growth Hormone Deficiency Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults. Effects of training duration on substrate turnover and oxidation during exercise. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults. Serum leptin concentrations during short-term administration of growth hormone and triiodothyronine in healthy adults: a randomised, double-blind placebo-controlled study. Strong diabetes 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. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Effects of growth hormone on renal tubular handling of sodium in healthy humans. Supraphysiological doses of GH induce rapid changes in cardiac morphology and function. Effects of growth hormone on serum lipids and lipoproteins: possible significance of increased peripheral conversion of thyroxine to triiodothyronine. A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers. Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion. Calorigenic effects of growth hormone: the role of thyroid hormones. Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults Acute effects of growth hormone on vascular function in human subjects. Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon. Body composition response to exogenous GH during training in highly conditioned adults. No effect of growth hormone administration on substrate oxidation during exercise in young, lean men. Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users. Effect of growth hormone and resistance exercise on muscle growth in young men. Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults. Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms. Effect of short-term treatment with recombinant human growth hormone on lipids and lipoproteins in women and men without growth hormone disturbances. 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. Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men. Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults Potential parameters for the detection of hGH doping Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Short-term recombinant human growth hormone administration improves respiratory function in abstinent anabolic-androgenic steroid users. Body fluids, circadian blood pressure and plasma renin during growth hormone administration: a placebo-controlled study with two growth hormone doses in healthy adults. The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group. Recombinant human growth hormone in abstinent androgenic-anabolic steroid use: psychological, endocrine and trophic factor effects.
abstract: The present study was design ed as a r and omized , double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration ( GH-adm . ) on energy expenditure ( EE ) and substrate oxidation in healthy humans . Sixteen young healthy men were divided into two groups . The study consisted of two 24-h measurements ( indirect calorimetry ) , separated by 2 wk of either Plc or GH injections ( 6 IU/day ) . At baseline , no significant differences were observed between the two groups in any of the measured anthropometric , hormonal , or metabolic parameters , neither did the parameters change over time in the Plc group . GH-adm . result ed in a 4.4 % increase in 24-h EE ( P < 0.05 ) and an increase in fat oxidation by 29 % ( P < 0.05 ) . However , a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast ( 0.84 + /- 0.1 to 0.79 + /- 0.1 , P < 0.05 ) . Furthermore , lean body mass ( LBM ) was increased by GH-adm . only [ 62.8 + /- 2.5 kg ( baseline ) vs. 64.7 + /- 2.4 kg ( after ) , P < 0.001 ] . In conclusion , GH-adm . increases 24-h EE , which may be partly explained by increased LBM . Furthermore , GH-adm . stimulates fat combustion , especially in the postabsorptive state 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 In a r and omized , double-blind , placebo-controlled , cross-over study , we examined the effects of 14 days of growth hormone ( GH ) administration ( 12 IU/d subcutaneously ) on  energy expenditure ( EE ) , respiratory exchange ratio ( RER ) , and thyroid function in 14 normal adults of normal weight ( eight men and six women ) .  EE ( kcal/24 h ) was significantly elevated after GH administration ( 2,073 + /- 392 , [ GH ] , 1,900 + /- 310 , [ placebo ] , P = .01 ) . RER was significantly lowered during GH administration ( 0.73 + /- 0.04 v 0.78 + /- 0.06 , P = .02 ) , reflecting increased oxidation of lipids . Total triiodothyronine ( TT3 ) ( nmol/L ) and free T3 ( FT3 ) ( pmol/L ) increased significantly during GH ( TT3 : 1.73 + /- 0.06 [ GH ] , 1.48 + /- 0.08 [ placebo ] , P = .01 ; FT3 : 6.19 + /- 0.56 [ GH ] , 5.49 + /- 0.56 [ placebo ] , P = .01 ) . Concomitantly , an insignificant decrease in reverse T3 ( rT3 ) ( nmol/L ) was observed ( 0.07 + /- 0.01 [ GH ] , 0.15 + /- 0.01 [ placebo ] , P = .08 ) . GH caused a highly significant increase in T3/thyroxine ( T4 ) ( x 100 ) ratio ( 1.84 + /- 0.12 [ GH ] , 1.37 + /- 0.06 [ placebo ] ) . Serum thyrotropin ( TSH ) was not significantly changed by GH . No changes in total thyroxine ( TT4 ) ( nmol/L ) ( 98 + /- 6 [ GH ] , 111 + /- 8 [ placebo ] , P = .40 ) and free thyroxine ( FT4 ) ( pmol/L ) ( 17.4 + /- 1.3 [ GH ] , 18.6 + /- 1.1 [ placebo ] , P = .37 ) after 14 days of GH administration were observed . In conclusion , 2 weeks of GH administration increases EE and lipidoxidation . This finding may partly be mediated by an increase in peripheral T4 to T3 conversion 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 The objective was to investigate the effect of growth hormone ( GH ) administration on circulating levels of free insulin-like growth factors ( IGFs ) in healthy adults . Eight healthy male subjects were given placebo and two doses of GH ( 3 and 6 IU/m2 per day ) for 14 days in a double-blind crossover study . Fasting blood sample s were obtained every second day . Free IGF-I and IGF-II were determined by ultrafiltration of serum . Total IGF-I and IGF-II were measured after acid-ethanol extraction . In addition , GH , insulin , IGF binding protein 1 ( IGFBP-1 ) and IGFBP-3 were measured . Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration . After 14 days , serum-free IGF-I values were 610 + /- 100 ng/l ( mean + /- SEM ) ( placebo ) , 2760 + /- 190 ng/l ( 3 IU/ m2 ) and 3720 + /- 240 ng/l ( 6 IU/m2 ) ( p = 0.0001 for 3 and 6 IU/m2 vs placebo ; p = 0.004 for 3 IU/m2 vs 6 IU/m2 ) . Total IGF-I values were 190 + /- 10 micrograms/l ( placebo ) , 525 + /- 10 ( 3 IU/m2 ) , and 655 + /- 40 micrograms/l ( 6 IU/m2 ) ( p < 0.0001 for 3 and 6 IU/m2 vs placebo ; p = 0.04 for 3 IU/m2 ) . There were no differences in the levels of free or total IGF-II during the three study periods . Insulin-like growth factor binding protein 1 was decreased during GH administration ( p = 0.04 for placebo vs 3 IU/m2 ; p = 0.006 for placebo vs 6 IU/m2 ) . In conclusion , fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1 Adaptations in fat and carbohydrates metabolism after a prolonged endurance training program were examined using stable isotope tracers of glucose ( [6,6 - 2H2]glucose ) , glycerol ( [2H5]glycerol ) , and palmitate ( [2H2]palmitate ) . Active , but untrained , males  exercised on a cycle for 2 h/day [ 60 % pretraining peak O2 consumption ( VO2peak ) = 44.3 + /- 2.4 ml.kg-1.min-1 ] for a total of 31 days . Three cycle tests ( 90 min at 60 % pretraining VO2peak ) were administered before training ( PRE ) and after 5 ( 5D ) and 31 ( 31D ) days of training . Exercise increased the rate of glucose production ( Ra ) and utilization ( Rd ) as well as the rate of lipolysis ( glycerol Ra ) and free fatty acid turnover ( FFARa/Rd ) . At 5D , training induced a 10 % ( P < 0.05 ) increase in total fat oxidation because of an increase in intramuscular triglyceride oxidation ( + 63 % , P < 0.05 ) and a decreased glycogen oxidation ( -16 % , P < 0.05 ) . At 31D , total fat oxidation during exercise increased a further 58 % ( P < 0.01 ) . The pattern of fat utilization during exercise at 31D showed a reduced reliance on plasma FFA oxidation ( FFA Rd ) and a greater dependence on oxidation of intramuscular triglyceride , which increased more than twofold ( P < 0.001 ) . In addition , glucose Ra and Rd were reduced at all time points during exercise at 31D compared with PRE and 5D . We conclude that long-term training induces a progressive increase in fat utilization mediated by a greater oxidation of fats from intramuscular sources and a reduction in glucose oxidation . Initial changes are present as early as 5D and occur before increases in muscle maximal mitochondrial enzyme activity High-dose GH administration is commonly associated with impaired insulin sensitivity ( S(I ) ) in humans . Paradoxically we have shown that low-dose GH ( 1.7 microg/kg.d ) administration enhances beta-cell function in young healthy adults . In the present double-blind , placebo-controlled , cross-over study , we explored the physiological effects of this low GH dose on glucose metabolism in 12 young healthy adults ( seven males , 19 - 29 yr ) . At pretreatment and after each 14-d treatment block ,  overnight metabolic profiles were assessed followed by a hyperinsulinemic euglycemic clamp , whereas fasting blood sample s were collected weekly . In subjects treated with GH first ( group A , n = 6 ) , GH treatment increased total IGF-I ( P < 0.05 ) and IGF binding protein-3 ( P < 0.01 ) after 7 d , but these levels subsequently returned to pretreatment levels after 14 d. In contrast , free IGF-I increased ( P < 0.05 ) , and overnight GH pulse peak amplitude decreased ( P < 0.01 ) after 14 d. In subjects treated with placebo first ( group B , n = 6 ) , all biochemical parameters were unchanged after placebo treatment , whereas the changes in free and total IGF-I were similar to those of group A after GH treatment . Combined clamp data from both groups A and B ( n = 12 ) showed that 14-d GH treatment decreased overnight plasma insulin levels ( P < 0.02 ) and hepatic glucose appearance ( P < 0.05 ) and increased S(I ) ( P < 0.01 ) . Of note , the GH-induced changes in S(I ) positively correlated with the changes in free IGF-I ( r = 0.72 , P < 0.01 ) . In conclusion , low-dose GH administration enhanced S(I ) and suppressed endogenous peak GH release , and we hypothesize that these effects are the direct result of increased serum levels of free The regulation of adipose tissue mass and energy expenditure is currently subject to intensive research , which primarily relates to the discovery of leptin . Leptin is a peptide , which is the product of the obese ( ob ) gene expressed in adipose tissue of several species icluding humans . Leptin is supposed to serve both as an index of fat mass and as a sensor of energy balance . Administration of recombinant murine leptin in ob/ob-mice , which do not produce leptin , decreases food intake and increases thermogenesis both of which result in a reduction in body weight and adipose tissue mass . The calorigenic effect of leptin presumably acts through an increase in sympathetic outflow which in turn activates the beta3 adrenergic receptor in brown adipose tissue . The regulation and action of endogenous leptin in humans are less well understood , and clinical grade recombinant human leptin is so far not available . Serum leptin correlates logarithmically with total body fat in both normal weight and obese subjects , which suggest insensitivity to leptin in obese patients . Furthermore , more rapid excursions in serum leptin have been reported following short-term changes in caloric intake and administration of insulin . Growth hormone ( GH ) exerts pronounced effects on lipid metabolism and resting energy expenditure . The lipolytic actions of GH appear to involve both increased sensitivity to the beta-adrenergic pathway , and a suppression of adipose tissue lipoprotein lipase activity . The calorigenic effects of GH have been shown not only to be secondary to changes in lean body mass . Growth hormone administration furthermore increases the peripheral conversion of thyroxine to triiodothyronine , which may contribute to the overall actions of GH on fuel and energy metabolism . So far , little is known about the effects of GH and iodothyronines on serum leptin levels in humans . We therefore measured serum leptin levels and energy expenditure before and after the administration of GH and triiodothyronine , alone and in combinaion , in a r and omized double-blind placebo-controlled study in healthy young male adults . The dose of triiodothyronine was selected to obtain serum levels comparable to those seen after GH administration The case of a 36-year-old male professional bodybuilder is reported . He presented to the accident and emergency department with right upper quadrant pain . This was on the background of a 15-year history of anabolic steroid and growth hormone misuse . Examination revealed mild hepatomegaly and a r and om blood sugar of 30.2 mmol/l . There was no evidence of ketonuria or acidosis . Biochemical evidence of hepatitis was found , and the patient was in acute renal failure . He was given a sliding scale of insulin and an intravenous infusion of crystalloid . The hepatitis and hyperglycaemia settled with conservative treatment . It is believed that this is the first reported case of frank diabetes precipitated by supraphysiological recreational growth hormone misuse 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 Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists To investigate the mechanisms behind the water- and sodium-retaining effects of growth hormone ( GH ) , we studied the effect of GH on 1 ) water and sodium homeostasis , 2 ) the renin-angiotensin-aldosterone system ( RAAS ) , and 3 ) lithium clearance ( C(Li ) ) with and without concomitant prostagl and in ( PG ) synthesis inhibition with ibuprofen . GH administration for 6 days induced a significant increase in plasma renin , which was abolished by coadministration of ibuprofen ( mU x l(-1 ) x 24 h(-1 ) : control : 22.4 + /- 4.3 ; GH : 37.7 + /- 8.8 ; ibuprofen : 15.2 + /- 3.0 ; GH + ibuprofen : 19.7 + /- 2.5 ; ANOVA : P < 0.01 ) . Comparable increments in extracellular volume were seen after 6-day treatment with GH alone and in combination with ibuprofen [ liters : control , 19.57 + /- 0.92 ; GH , 20.80 + /- 1.00 ( ANOVA : P < 0.0005 ) ; ibuprofen , 19.38 + /- 0.90 ; GH + ibuprofen , 21.63 + /- 1.37 ( ANOVA : P < 0.0005 ) ] . Treatment with GH increased C(Li ) and changed the tubular h and ling of sodium and water . The absolute distal sodium reabsorption was increased , and this was only partially counterbalanced by decreased reabsorption in the proximal tubules . The data demonstrate that GH-induced activation of the RAAS can be blocked by concomitant PG synthesis inhibition and that the tubular effects of GH include increased distal nephron sodium and water reabsorption GH is an agent widely used in sport to improve physical performance and has been proposed as adjunctive therapy in several clinical conditions . However , its short-term effects on the normal human heart are poorly understood . Sixty young normal volunteers ( 30 males and 30 females ) were enrolled in a multicenter , double-blind , placebo-controlled study . All subjects were r and omized to receive  GH ( 0.03 or 0.06 mg/kg.d ) or placebo . A complete Doppler-echocardiographic examination was performed at baseline and after 4 wk of treatment . Low-dose GH did not significantly affect echocardiographic parameters . In contrast , high-dose GH increased left ventricular mass index by 12 % ( P < 0.05 ) . The type of growth response was concentric , because left ventricular wall thickness but not diameter increased , leading to a 10 % increase of relative wall thickness . These structural changes were associated with functional changes , including a significant increase in cardiac index and a decrease in peripheral vascular resistance ; diastolic function was not altered . Fractional shortening and systemic blood pressure were unchanged in the two treatment groups . In conclusion , administration of GH for 4 wk at doses that simulate GH abuse in sport caused a high cardiac output state associated with concentric left ventricular remodeling The role of growth hormone ( GH ) and thyroid hormone in the regulation of lipid and lipoprotein metabolism is not fully established . Furthermore , the possible linkage between the well-known GH-induced increase in peripheral thyroxine ( T4 ) to triiodothyronine ( T3 ) generation and the effects of GH on lipid and lipoprotein metabolism has not been eluci date d. In this double-blind placebo-controlled study , we compared the effects of GH and T3 administration alone and in combination on lipid and lipoprotein metabolism in a group of healthy young adults . The dose of T3 was selected to mimic the T2 increase seen during exogenous GH exposure . Eight normal male subjects ( aged 21 to 27 years ; body mass index , 21.11 to 27.17 kg/m2 ) were r and omly studied during four 10-day treatment periods with ( 1 ) daily subcutaneous placebo injections and placebo injections and placebo tablets , ( 2 ) daily subcutaneous GH injections ( 0.1 IU/kg.d ) and placebo tablets , ( 3 ) daily T3 administration ( 40 micrograms on even date s or 20 micrograms on uneven date s ) plus placebo injections , and ( 4 ) daily GH injections plus T3 administration . GH administration increased free T3 ( FT3 ) to the same level as during T3 administration . GH caused decreased levels of total cholesterol ( TC ) and low-density lipoprotein ( LDL ) cholesterol and increased levels of triglycerides ( TG ) and lipoprotein(a ) ( Lp(a ) ) , but no changes in high-density lipoprotein ( HDL ) cholesterol and apolipoprotein B ( apo B ) . T3 administration caused no alteration in these parameters , except for decreased levels of TC comparable to those seen after GH administration . Combined GH and T3 administration caused changes identical to those seen after GH administration , in addition to decreased apo B levels and a further decrease of TC levels . We conclude that GH and iodothyronines in the physiologic range exert distinct but disparate effects on lipids and lipoproteins , and do not support the hypothesis that the effects observed during GH administration are exclusively secondary to changes in peripheral T3 levels The effects of recombinant human growth hormone ( rhGH ) on biochemical markers of bone turnover and bone mineral content ( BMC ) were investigated in 20 normal male volunteers ( aged 22 - 31 years ) r and omized to treatment for 7 days with either rhGH  ( 0.1 IU/kg subcutaneously twice a day ) or placebo .  Serum somatomedin C rose during treatment ( p less than 0.001 ) but was not significantly different from baseline at day 14 . The fasting urinary hydroxyproline/creatinine ( p less than 0.001 ) and calcium/creatinine ratios ( p less than 0.01 ) increased during treatment and remained elevated for 4 and 2 weeks , respectively . Serum bone gamma-carboxyglutamic acid-containing protein ( BGP ) increased during treatment ( p less than 0.001 ) and remained elevated for 6 months ( p less than 0.02 ) . Serum bone alkaline phosphatase ( B-AP ) , after an initial fall in the treatment period ( p less than 0.001 ) , increased slightly in the following months ( p less than 0.01 ) . In the rhGH group BMC was significantly higher than the pre study value at day 14 ( p less than 0.05 ) but was unaltered at the end of study . The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling 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 GH administration increases energy expenditure , independent of changes in lean body mass , in healthy , obese , and GH-deficient subjects . This may be causally linked to the well known GH-induced increase in peripheral T4 to T3 generation , but experimental data are sparse . In this study we have addressed whether 1 ) the calorigenic effects of GH administration could be reproduced by oral supplementation of T3 in a dose selected to mimic the GH-induced increase in peripheral T3 levels ; and 2 ) combined GH and T3 administration have a synergistic effect on resting energy expenditure ( REE ) .  Eight normal male subjects ( aged 21 - 27 yr ; body mass index , 21.11 - 27.17 kg/m2 ) were r and omly studied during four 10-day treatment periods with 1 ) daily sc placebo injections and placebo tablets , 2 ) daily sc GH injections ( 0.1 IU/kg x day ) and placebo tablets , 3 ) daily T3 administration ( 40 microg on even date s , 20 microg on uneven date s ) plus placebo injections , and 4 ) daily GH injections plus T3 administration . GH administration increased both free T3 ( FT3 ) levels [ mean + /- SE , 6.2 + /- 0.3 ( control ) vs. 7.3 + /- 0.5 ( GH ) pmol/L ; P < 0.05 ] and REE [ mean + /- SE , 1959 + /- 67 ( control ) vs. 2164 + /- 55 ( GH ) Cal/24 h ; P < 0.01 ] . T3 administration yielded comparable levels of FT3 ( 7.7 + /- 0.5 pmol/L ; T3 vs. GH , P = 0.37 ) , but did not increase REE ( 2015 + /- 48 Cal/24 h ; T3 vs. control , P = 0.23 ) . Combined GH and T3 administration increased REE to a level higher than that seen with T3 alone ( 2279 + /- 68 Cal/24 h ; T3 vs. GH plus T3 , P < 0.01 ) . Significant increments in serum levels of insulin-like growth factor I and insulin were recorded with GH administration , but not with T3 alone . Resting heart rate increased to a similar degree after GH administration and T3 supplementation , respectively . Tympanic temperature remained unaltered in all four studies . The results suggest that the calorigenic effect of GH is not mediated solely through increased conversion of T4 to T3 Objectives To study the effects on body composition after 1 month 's administration of supraphysiological doses of growth hormone ( GH ) in healthy , active young adults with normal GH‐IGF‐I axis GH is involved in the long-term regulation of peripheral vascular resistance and vascular reactivity . We determined whether GH plays a role in the acute regulation of vascular function in humans . The acute vascular effects of GH were studied in eight healthy subjects according to a double-blind , placebo-controlled design . Forearm blood flow ( FBF ) , vascular resistance , and nitric oxide ( NO ) production were monitored during a 4-h infusion of GH into the brachial artery at a rate chosen to raise local GH to stress levels ( approximately 40 ng/ml ) . During GH infusion , FBF rose 75 % ( P < 0.05 ) , whereas forearm vascular resistance decreased comparably ( P < 0.05 ) . These changes were paralleled by augmented forearm release of NO ( P < 0.02 ) . GH heightened the response of FBF to the endothelium-dependent vasodilator acetylcholine ( Ach ; P < 0.02 ) . With the highest Ach dose , FBF reached 30.4 + /- 4.2 and 16.9 + /- 3.1 ml/dl x min in the GH and placebo studies , respectively ( P < 0.005 ) . The slopes of the dose-response curves also differed markedly ( 0.45 + /- 0.07 and 0.25 + /- 0.05 ml/dl x min/ microg in the GH and placebo studies , respectively ; P < 0.01 ) . GH caused an upward shift of the FBF response to the endothelium-independent vasodilator sodium nitroprusside ( P < 0.01 ) , but did not affect the slope of the dose-response curve . GH infusion did not cause any appreciable increment in the venous IGF-I concentration in the test arm . In conclusion , GH acutely lowers peripheral vascular resistance and stimulates endothelial function . These effects are mediated by activation of the NO pathway and appear to be independent of We measured changes in serum insulin-like growth factor-1 ( IGF-1 ) , calcitriol , parathyroid hormone ( PTH ) , thyroid hormones , insulin , and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone ( r-hGH ) ( 0.1 IU/kg sc twice daily ) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones . Serum IGF-1 ( p < 0.001 ) and vitamin D-binding protein ( p < 0.001 ) increased steadily during treatment returning to baseline at day 14 . Total calcitriol ( p < 0.01 ) and free calcitriol index ( p < 0.001 ) increased transiently at day 4 . Furthermore , serum insulin ( p < 0.001 ) and both total ( p < 0.001 ) and free triiodothyronine ( p < 0.02 ) increased during treatment , while serum PTH and plasma glucagon remained unchanged . In conclusion , pharmacological doses of r-hGH increased not only IGF-1 but also free-calcitriol index , insulin , and free T3 . The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis 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 The purpose of this study was to examine the effects of increased fat availability induced by growth hormone ( GH ) administration on the oxidative metabolism during exercise . Seven well-trained males ( age 25 + /- 2 years ( mean + /- S.E.M. ) ; peak oxygen consumption : 62 + /- 1 ml min(-1 ) kg(-1 ) ( completed four r and omised trials : 120 min bicycling at 55 % 4 h after receiving either 7.5 IU ( 2.5 mg ) GH or placebo ( Plc ) , and during rest after receiving either GH or Plc . In all studies a st and ardized meal was given 2 h after GH or Plc injection . GH administration result ed in an approximately 60-fold increase in serum GH concentration at rest ( P < 0.0001 ) and during exercise ( P < 0.0001 ) . The increase in serum GH was followed by an increase in circulating glycerol at rest ( 8 % , P < 0.0001 ) . When combined with exercise the increase in plasma glycerol was more pronounced  ( GH : 716 % of baseline versus Plc : 328 % , P < 0.0001 ) . However , this increase in fat mobilization did not increase fat oxidation during exercise ( indirect calorimetry ) . In conclusion , GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone , but did not further augment whole body fat oxidation 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 The purpose of this study was to determine whether growth hormone ( GH ) administration enhances the muscle anabolism associated with heavy-resistance exercise . Sixteen men ( 21 - 34 yr ) were assigned r and omly to a resistance training plus GH group ( n = 7 ) or to a resistance training plus placebo group ( n = 9 ) . For 12 wk , both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo . Fat-free mass ( FFM ) and total body water increased ( P less than 0.05 ) in both groups but more ( P less than 0.01 ) in the GH recipients . Whole body protein synthesis rate increased more ( P less than 0.03 ) , and whole body protein balance was greater ( P = 0.01 ) in the GH-treated group , but quadriceps muscle protein synthesis rate , torso and limb circumferences , and muscle strength did not increase more in the GH-treated group . In the young men studied , resistance exercise with or without GH result ed in similar increments in muscle size , strength , and muscle protein synthesis , indicating that 1 ) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2 ) resistance training supplemented with GH did not further enhance muscle anabolism and function GH deficiency ( GHD ) in adulthood is accompanied by physical and psychological impairments . One hundred fifteen patients ( 67 male , 48 female ) with pronounced GHD were enrolled in a r and omized , double-blind , placebo-controlled study with objectives that included effects on body composition , cardiac structure , and function and safety of replacement therapy with recombinant human GH ( Saizen ) . Sixty patients ( 31 male , 29 female ) received GH at a dose of 0.005 - 0.010 mg/kg.d , and 55 patients ( 36 male , 19 female ) received placebo for 6 months . Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg ( between-group comparison , P < 0.0001 ) , which was significantly greater among males than females ( P < 0.0001 ) [ males : GH , + 3.13 kg ( 2.42 , 3.84 ) ; placebo , + 0.11 kg ( -0.60 , 0.82 ) ; and females : GH , + 0.64 kg ( -0.15 , 1.44 ) ; placebo : -0.90 kg ( -2.20 , 0.39 ) ] [ mean change 0 - 6 months ( 95 % confidence limits ) ] and was associated with IGF-I changes . The decrease in fat mass of 2.8 kg ( between-group comparison , P < 0.0001 ) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements . Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders . End-systolic volume decreased by 4.3 + /- 10.5 ml ( from 35.8 + /- 17.6 ml ; between-group comparison , P = 0.035 ) and ejection fraction increased by 5.1 + /- 10.0 % ( from 55.0 + /- 11.2 % ; between-group comparison , P = 0.048 ) , approaching normalcy . Diastolic function did not change as assessed by isovolumic relaxation time , early diastolic flow , diastolic flow secondary to atrial contraction , or ratio of peak mitral early diastolic and atrial contraction velocity .  GH treatment was well tolerated , with adverse events primarily related to effects on fluid balance . No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified . In conclusion , GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females . In contrast , cardiac function improvement appears to benefit both genders equally Sodium retention and symptoms and signs of fluid retention are commonly recorded during GH administration in both GH-deficient patients and normal subjects . Most reports have however , been casuistic or uncontrolled . In a r and omized double blind placebo-controlled cross-over study we therefore examined the effect of 14-day GH administration ( 12 IU sc at 2000 h ) on plasma volume , extracellular volume ( ECV ) , atrial natriuretic peptide ( ANP ) , arginine vasopressin , and the renin angiotensin system in eight healthy adult men . A significant GH induced increase in serum insulin growth factor I was observed . GH caused a significant increase in ECV ( L ) : 20.45 + /- 0.45 ( GH ) , 19.53 + /- 0.48 ( placebo ) ( P less than 0.01 ) , whereas plasma volume ( L ) remained unchanged 3.92 + /- 0.16 ( GH ) , 4.02 + /- 0.13 ( placebo ) . A significant decrease in plasma ANP ( pmol/L ) after GH administration was observed : 2.28 + /- 0.54 ( GH ) , 3.16 + /- 0.53 ( placebo ) P less than 0.01 . Plasma aldosterone ( pmol/L ) : 129 + /- 14 ( GH ) , 89 + /- 17 ( placebo ) , P = 0.08 , and plasma angiotensin II ( pmol/L ) levels : 18 + /- 12 ( GH ) , 14 + /- 7 ( placebo ) , P = 0.21 , were not significantly elevated . No changes in plasma arginine vasopressin occurred ( 1.86 + /- 0.05 pmol/L vs. 1.90 + /- 0.05 , P = 0.33 ) . Serum sodium and blood pressure remained unaffected . Moderate complaints , which could be ascribed to water retention , were recorded in four subjects [ periorbital edema ( n = 3 ) , acral paraesthesia ( n = 2 ) and light articular pain ( n = 1 ) ] . The symptoms were most pronounced after 2 - 3 days of treatment and diminished at the end of the period . In summary , 14 days of high dose GH administration caused a significant increase in ECV and a significant suppression of ANP In a double blind , cross-over placebo-controlled trial , we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition , metabolic parameters , and well-being in 10 patients with adult-onset GH deficiency ( GHD ) . All patients received appropriate thyroid , adrenal , and gonadal replacement therapy . The dose of recombinant human GH was 0.25 - 0.5 U/kg.week ( 0.013 - 0.026 mg/kg.day ) and was administered sc daily at bedtime . One patient was withdrawn from the study because of edema and atrial fibrillation . Body composition was estimated with three independent methods : computed tomography , bioelectric impedance , and total body potassium combined with total body water assessment s. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology . After 26 weeks of treatment , adipose tissue ( AT ) mass decreased 4.7 kg ( P < 0.001 ) . Subcutaneous AT decreased by an average of 13 % , whereas visceral AT was reduced by 30 % . Muscle volume increased by 2.5 kg ( 5 % ; P < 0.05 ) . According to the four-compartment model derived from assessment s of total body potassium and total body water , body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg , whereas body fat decreased by 6.1 kg . Results obtained by the bioelectric impedance technique were similar . The mean ( + /- SD ) concentrations of insulin-like growth factor-I increased from 0.26 ( 0.06 ) at baseline to 2.56 ( 1.55 ) and 2.09 ( 1.03 ) kU/L after 6 and 26 weeks of treatment . Calcium and serum phosphate , osteocalcin , and procollagen-III concentrations were significantly higher , and intact PTH concentrations were reduced after 6 and 26 weeks of treatment , respectively . Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment , whereas free T4 concentrations were reduced at 6 weeks , but after 26 weeks , free T4 concentrations had returned to pretreatment values . Finally , after 26 weeks of treatment , there was a decrease in the Comprehensive Psychological Rating Scale score ( P < 0.05 ) . The results show that GH replacement in GHD adults results in marked alterations in body composition , fat distribution , and bone and mineral metabolism and reduces psychiatric symptoms . Finally , we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults The aim of GH replacement therapy in GH-deficient adults is to optimize response with minimum incidence of adverse reactions , but optimal therapy regimens are still to be established . This two-arm parallel study examined effects of two GH dose algorithms in adults with GH deficiency of adult or childhood onset . Patients on low dose ( LD ; n = 302 )  received GH at 3 microg/kg per day for 3 months increasing to 6 microg/kg per day for 3 months , and those on conventional dose ( CD ; n = 293 ) started on 6 microg/kg per day for 3 months increasing to 12 microg/kg per day for 3 months . The proportion of patients completing therapy was greater for the LD group than the CD group for the first 3 months ( 93.0 % vs. 88.1 % ; P = 0.037 ) and overall for the 6 months ( 90.7 % vs. 84.0 % ; P = 0.013 ) . Both dose groups showed significant increases in lean body mass and decreases in fat mass for all time points . Percent increase in lean body mass was less with LD than CD over the first 3 months ( 2.43 + /- 4.33 vs. 3.58 + /- 4.69 % ; P = 0.006 ) but not overall for the 6-month period ( 4.38 % + /- 5.34 % vs. 5.21 % + /- 5.99 % ; P = 0.141 ) . Percent decrease in fat mass was less with LD than CD for the first 3 months ( -2.81 % + /- 7.81 % vs. -5.53 % + /- 8.64 % ; P < 0.001 ) and overall for the 6-month period ( -6.35 % + /- 9.42 % vs. -9.45 % + /- 12.07 % ; P = 0.006 ) . IGF-I SD score increased less with LD than CD for 0 to 3 and 0 to 6 months , although for IGF-binding protein-3 SD score , there was no significant difference between doses at any time . Arthralgia was the only adverse event that occurred significantly less frequently with LD than with CD . Calculated changes based on gender and onset indicated greater changes in males than females for body composition , but there was little difference in GH-related adverse events between males and females . The lower starting dose with dose titration appeared more favorable , but differences in response between genders and onset of GH deficiency need to be taken into account when setting an individual dose regimen The effect of recombinant human growth hormone ( rHGH ) on cholesterol , high- and low-density lipoprotein ( HDL and LDL ) cholesterol , triglycerides ( TG ) , apolipoprotein ( apo ) B , apo A-I , and lipoprotein(a ) [ Lp(a ) ] was studied in 40 postmenopausal women treated with 0.05 , 0.1 , or 0.2 IU/kg/d rHGH or placebo for 7 days .  Cholesterol , LDL cholesterol , and HDL cholesterol decreased in a dose-dependent manner ( P = .001 , P = .001 , and P = .003 , respectively ) , whereas apo B decreased insignificantly ( P = .15 ) . Apo A-I decreased significantly only among women treated with rHGH at a dose of 0.1 IU/kg/d ( P = .03 ) . When all rHGH-treated women were grouped together , Lp(a ) increased ( P = .001 ) . We also studied 20 young men treated with either 0.2 IU/kg/d rHGH or placebo .  As in women , cholesterol and apo B decreased P = .005 and P = .02 , respectively ) , whereas Lp(a ) increased ( P = .05 ) . There was no detectable effect of rHGH on TG concentrations in men . As in women , there was no significant effect of 0.2 IU/kg/d rHGH on apo A-I concentrations . All lipid and lipoprotein measures reached pretreatment levels during the first week after treatment was stopped , except Lp(a ) , which remained elevated 2 weeks after rHGH cessation 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 We studied the acute effects of a single , sc GH dose on exercise performance and metabolism during bicycling . Seven highly trained men [ age , 26 + /- 1 yr ( mean + /- SEM ) ; weight , 77 + /- 3 kg ; maximal oxygen uptake , 65 + /- 1 ml O(2).min(-1).kg(-1 ) ] performed 90 min of bicycling 4 h after receiving 7.5 IU ( 2.5 mg ) GH or placebo in a r and omized , double-blinded , cross-over design trial . A st and ardized pre-exercise meal was given 2 h before exercise . Blood was sample d at rest and during exercise and analyzed for GH , IGF-I , glucose , lactate , insulin , glycerol , and nonesterified fatty acids ( NEFA ) . In the placebo trial , all subjects completed the exercise protocol without any difficulties . In contrast , two subjects were not able to complete the exercise protocol in the GH trial , and one subject barely managed to complete the protocol . In addition , GH administration result ed in exaggerated increases in plasma lactate concentrations during exercise ( P < 0.0001 ) . The combined lipolytic effect of GH and exercise , evidence d by increased plasma glycerol and serum NEFA concentrations , was 3-fold greater than the effect of exercise alone ( P < 0.0001 ) , but this increased substrate availability did not result in increased whole body fat oxidation ( indirect calorimetry ) . Plasma glucose was , on average , 9 % higher during exercise after GH administration compared with placebo ( P < 0.0001 ) . We conclude that a single , relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity . The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance Objectives Exercise is a potent physiological stimulus of GH secretion . We hypothesized that exogenous recombinant human growth hormone ( rhGH ) administration through an increase in GH and IGF‐I levels would blunt the GH response to exercise . The aim of the study was to examine and compare the impact of rhGH on the exercise‐induced GH response in healthy normal men and women The aim of our hGH application study with non-competitive athletes was the investigation of selected serum parameters from different processes affected by hGH . Fifteen athletes ( age 21–33 , mean 24 ) were treated with 0.06 IU hGH/kg BW per day or placebo ( 10 hGH , 5 placebo ) respectively for 14 days . Blood sample s were taken prior to , during and until 10 weeks after treatment . The concentrations of the following markers were determined in relevant serum sample s : IGF-I , IGFBP-3 , ALS , PIIINP , PINP , osteocalcin , and leptin . The IGF-I concentration increased rapidly within the hGH treatment group and showed significantly higher levels compared to baseline even 3 days after application . The response of the IGFBP-3 to the hGH applications was lower in comparison to IGF-I. The hGH group showed an increasing IGFBP-3 compared to baseline from day 4 till day 15 . The response of PIIINP to hGH is clearly delayed compared to the IGF-I axis , but the PIIINP concentration remains on an increased level for a longer period ( from day 4 until day 21 ) . The time course and the extent of response varied strongly interindividually . PINP and osteocalcin showed only a small response to hGH applications . These parameters are characterised by a strong scattering of base values compared with the small response . In the hGH treatment group very different leptin concentrations were found at the beginning of the study , but after treatment decreasing leptin levels were observed in all cases . The determination of only one parameter will not be sufficient for detection of hGH abuse . A combination of markers by mathematical methods can be helpful to distinguish between placebo and hGH-treated athletes . By using the suggested discriminant function the data sets of hGH and placebo-treated athletes could be separated without false positive results 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 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 Side effects that can be related to fluid retention are common during the initial phases of growth hormone ( GH ) administration . The aim of this study was to examine the changes in body fluid compartments , diurnal blood pressure and plasma renin concentration during GH administration with two different dosages in healthy adults . Eight healthy male subjects aged 24 - 32 years were examined during three 2-week study periods in a double-blind placebo controlled study . They received , in r and om order , GH ( 3 or 6 IU m-2 daily ) or placebo during 2 weeks . Bio-impedance was measured every 2nd day , and extracellular volume ( ECV ) and plasma volume ( PV ) were isotopically determined at day 6 . Blood sample s were obtained regularly . Diurnal blood pressure was recorded and 24-h urinary sample s were collected at days 0 , 6 and 14 . ECV ( l ) was increased by GH ( placebo , 19.58 + /- 0.82 ; 3 IU m-2 , 20.77 + /- 1.22 ; 6 IU m-2 , 20.65 + /- 0.94 ; p<0.01 ) , whereas PV ( l ) was unaffected ( placebo , 3.91+/- 0.20 ; 3 IU m-2 , 4.04 + /- 0.22 ; 6 IU m-2 , 3.90 + /- 0.27 ) . Total body water ( l ) increased significantly during GH administration ( placebo , 50.8 + /- 2.6 ; 3 IU m-2 , 52.6 + /- 2.3 ; 6 IU m-2 , 53.9 + /- 1.8 , p<0.05 ) . After 6 days of treatment a significant increase in renin ( p = 0.03 ) was observed . Mean diurnal blood pressure levels remained unchanged , whereas mean diurnal heart rate ( min-1 ) increased significantly ( placebo , 75 + /- 3.6 ; 3 IU m-2 , 79 + /- 3.2 ; 6 IU m-2 , 79 + /- 3.7 ; p<0.01 ) . In conclusion , GH administration induces an elevation in total body water which may involve a stimulation of plasma renin and an increased ECV without any changes in PV or diurnal blood pressure Measurements of serum insulin-like growth factor I ( IGF-I ) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess . The validity of these markers for assessment of exogenous GH exposure in healthy adults is , however , unknown . We therefore conducted a double blind , placebo-controlled GH treatment trial in 99 healthy subjects [ 49 women and 50 men ; mean + /- SE age , 25.6+/-0.6 (women)/25.7+/-0.6 yr ( men ) ] .  Blood  was collected weekly during a 4-week treatment period ( days 1 - 28 ) , and the subjects were subsequently followed for additional 8 weeks ( days 29 - 84 ) . The treatment arms included : I ) 0.1 IU/kg x day GH ( n = 30 ; GH 0.1 ) , II ) 0.2 IU/kg x day GH ( n = 29 ; GH 0.2 ) , and III ) placebo ( n = 40 ) . At baseline no gender-specific differences existed , except that the acid-labile subunit ( ALS ) levels were higher in females . Serum insulin-like growth factor I ( IGF-I ) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses . The absolute IGF-I response was significantly lower in females , and there was a clear dose-response relationship . ALS levels in males increased through day 30 ( P < 0.001 ) . In females ALS levels were only modestly increased on day 28 compared with those in the placebo group ( P < 0.02 ) . IGF-binding protein-3 ( IGFBP-3 ) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 ( P < 0.03 ) , whereas no solid IGFBP-3 increase was detected in females . IGFBP-2 levels decreased insignificantly during GH exposure in both genders . A gender-specific upper normal range for each analyte was arbitrarily defined as 4 SD above the mean level at baseline . On the basis of IGF-I levels alone , GH exposure in the GH 0.2 group was detected in 86 % of the males and in 50 % of the females on day 21 . On day 42 GH exposure was only weakly detectable in males and was not detectable in females . We conclude that 1 ) males are significantly more responsive than females to exogenous GH ; 2 ) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS ; 3 ) IGFBP-2 changes very little during GH treatment ; and 4 ) among IGF-related substances , IGF-I is the most specific marker of supraphysiological GH exposure 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
target: Some have suggested that growth hormone is a wonder drug ( 16 ) that results in ripped muscle ( 17 ) and provides stamina-increasing properties ( 18 ) .
background: 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 .