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 .
Effects of Physiologic Growth Hormone Therapy on Bone Density and Body Composition in Patients with Adult-Onset Growth Hormone Deficiency
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
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 .