Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability Effects of Physiologic Growth Hormone Therapy on Bone Density and Body Composition in Patients with Adult-Onset Growth Hormone Deficiency Effects of protein supplementation on muscular performance and resting hormonal changes in college football players. Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Body composition and quality of life in adults with growth hormone deficiency; effects of low‐dose growth hormone replacement Effect of growth hormone and resistance exercise on muscle growth in young men. Hormonal responses in athletes: the use of a two bout exercise protocol to detect subtle differences in (over)training status Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. Growth hormone treatment and fat redistribution in children born small for gestational age. Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults Growth hormone treatment of children with Prader‐Willi syndrome affects linear growth and body composition favourably Growth hormone plus childhood low-dose estrogen in Turner's syndrome. Attenuation of Posttraumatic Muscle Catabolism and Osteopenia by Long-Term Growth Hormone Therapy A New Treatment for Patients with Short‐Bowel Syndrome Growth Hormone, Glutamine, and a Modified Diet Enhanced neuroendocrine response to insulin tolerance test performed under increased ambient temperature 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 Growth hormone treatment in pediatric burns: a safe therapeutic approach. Monitoring performance, pituitary–adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players Growth hormone response to sodium valproate in chronic schizophrenia Acute hormonal responses following different velocities of eccentric exercise Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year. Effects of resistance training under hypoxic conditions on muscle hypertrophy and strength Effect of growth hormone, glutamine, and diet on body composition in short bowel syndrome: a randomized, controlled study. Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women. Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. Growth hormone, prolactin and cortisol response to exercise in patients with depression. Serum leptin concentrations during short-term administration of growth hormone and triiodothyronine in healthy adults: a randomised, double-blind placebo-controlled study. Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis. A longitudinal study of craniofacial growth in idiopathic short stature and growth hormone-deficient boys treated with growth hormone. Longitudinal measures of circulating leptin and ghrelin concentrations are associated with the growth of young Peruvian children but are not affected by zinc supplementation. The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double-blind, placebo-controlled study Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome. BENEFICIAL EFFECTS OF GROWTH HORMONE TREATMENT IN GH-DEFICIENT ADULTS Synthetic human growth hormone releasing factor (h-GRF-I-44-NH2) dose response effect on growth hormone and prolactin secretion in healthy adult men Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term prospective study using dynamic endocrine testing.
Aging is associated with alterations in body composition and a decline in functional status . Healthy older persons have decreased muscle mass , increased fat mass , and decreased strength [ 1 - 3 ] . The muscle strength of 70-year-old men is about half that of young adults [ 3 ] . The risk for falls , fractures , and frailty increases with age-related decreases in muscle strength [ 4 - 6 ] . Pituitary secretion of growth hormone and circulating levels of insulin-like growth factor 1 decrease with aging [ 7 ] ; these events are called somatopause . Growth hormone is both anabolic and lipolytic [ 8 - 10 ] , and the action of growth hormone on peripheral tissues is mediated , in part , by circulating insulin-like growth factor 1 [ 11 ] . Growth hormone deficiency results in body composition changes that are similar to the changes seen with aging [ 1 , 7 ] . Growth hormone replacement in patients with hypopituitarism and in older men reverses some of the body composition changes associated with both growth hormone deficiency and aging [ 12 - 14 ] . In a study by Rudman and colleagues [ 14 ] on the effects of growth hormone replacement therapy on body composition , the administration of growth hormone to 12 men 61 to 73 years of age for 6 months increased lean body mass by 9 % and decreased adipose tissue mass by 15 % ( P < 0.005 ) . Circulating insulin-like growth factor 1 levels increase similarly in young and old men after exogenous administration of either growth hormone or growth hormone-releasing hormone [ 7 , 11 ] . Therefore , low insulin-like growth factor 1 levels reflect decreased growth hormone secretion rather than a loss of hepatic responsiveness to the hormone . On the basis of these data , it has been proposed that diminished secretion of growth hormone is responsible , in part , for the somatic changes of aging [ 14 ] . Growth hormone replacement has been shown to improve muscle volume , isometric strength , and exercise capacity in young adults with hypopituitarism [ 12 , 13 ] . In one study of growth hormone-deficient young adults treated with growth hormone [ 12 ] , thigh muscle volume increased by 6 % ( P < 0.01 ) , and isometric strength increased by 8 % ( P = 0.08 ) compared with controls . Increases in isometric strength were associated with increases in muscle volume ( r = 0.75 ; P < 0.001 ) . Exercise capacity also increased by 12 % ( P < 0.05 ) . Such data on the effects of growth hormone replacement therapy on strength or function are not available for older persons . To test the hypothesis that the muscle weakness and functional decline associated with aging are in part due to decreased growth hormone secretion , we conducted a 6-month r and omized , controlled , double-blind trial comparing recombinant human growth hormone therapy with placebo in 56 elderly men whose baseline insulin-like growth factor 1 levels were less than the tenth percentile found in younger healthy adults . Methods Participants We recruited healthy , ambulatory , community-dwelling men older than 69 years of age . Because growth hormone secretion is pulsatile and diurnal , a more convenient measure of growth hormone secretion is insulin-like growth factor 1 , which has constant and nonpulsatile plasma levels [ 1 , 7 , 15 , 16 ] . Inclusion criteria included two fasting morning plasma insulin-like growth factor 1 levels ( assayed after plasma was extracted with acid ethanol by the Nichols Institute [ 17 ] ) less than 161 ng/mL that were obtained at least 2 weeks apart , a fasting blood glucose level less than 8.4 mmol/L ( 140 mg/dL ) , stable body weight between 80 % and 120 % of ideal body weight [ 18 ] during the previous year , and a normal complete blood count at baseline . Participants had to be able to follow the study instructions and perform the strength measurements . Exclusion criteria included diseases that might contraindicate the use of growth hormone ( such as carcinoma within the previous 5 years , diabetes mellitus , and the carpal tunnel syndrome ) , uncontrolled hypertension ( blood pressure more than 180/100 mm Hg ) , oral corticosteroid use within the previous year , or a recent change in ambulatory status ( for example , as the result of a stroke ) . Design After the participants gave informed written consent , the following baseline measurements were obtained : question naires ( demographic characteristics and medical conditions ) ; fasting blood chemistry ( levels of electrolytes , urea nitrogen , creatinine , glucose , calcium , phosphate , and albumin ) ; complete blood count ; serum and rogen levels ( total and free testosterone and dehydroepi and rosterone ) ; fasting lipoprotein levels ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and triglycerides ) and thyroid-stimulating hormone and free thyroxine levels ; 24-hour urinary calcium excretion ; and creatinine clearance . At baseline , we also measured the body composition , strength , and functional ability of all participants . We then used a computer-generated r and omization table to assign each participant to receive either growth hormone or placebo . Participants , investigators who had contact with the participants , and laboratory personnel were blinded to treatment status . Treatment consisted of recombinant human growth hormone ( somatropin [ Nutropin , Genentech ] ) , 0.03 mg/kg of body weight , or an equivalent placebo volume ( supplied in identical vials by Genentech ) injected subcutaneously three times per week in the morning for 6 months . We evaluated the participants after 2 , 4 , 8 , 12 , 18 , and 24 weeks of treatment to determine whether side effects developed and to ensure compliance . Participants were examined and specifically asked about the presence of the following side effects : malaise , fatigue , edema , arthralgias , arthritis , the carpal tunnel syndrome , muscle discomfort , dyspnea , depression , polydipsia , polyuria , nocturia , and tender or enlarged breasts . At each visit , we measured fasting morning plasma insulin-like growth factor 1 levels 48 hours after the last treatment dose and repeated most of the baseline blood and urinary tests . We adjusted the dose of recombinant human growth hormone to maintain serum insulin-like growth factor 1 levels between 190 and 350 ng/mL ( the 25th to 75th percentiles of a young adult population ) 48 hours after a dose . To preserve blinding , each growth hormone recipient was paired with a placebo recipient . An unblinded physician who had not had contact with the participants review ed insulin-like growth factor 1 levels during the trial . If the levels were less than 190 ng/mL or greater than 350 ng/mL , the unblinded physician instructed study personnel to make identical dose adjustments for both participants in the pair . The dose was also decreased in any participant who reported troublesome side effects that were potentially attributable to growth hormone . We repeated all study outcome measurements after 6 months of treatment . We also measured fasting plasma renin activity , cortisol and aldosterone levels , and 24-hour urine aldosterone excretion . The investigational review boards of the University of California , San Francisco , and the Department of Veterans Affairs Medical Center , San Francisco , approved the study protocol . Measurements Body Composition We used dual-energy x-ray absorptiometry ( Lunar DPX-Plus , Madison , Wisconsin ) total-body composition scans to measure lean tissue mass and fat mass , and we used anterior-posterior lumbar scans to measure bone mineral content . We measured skin thickness using ultrasonography with a 10-MHz transducer ( Diasonics , Milpitas , California ) that was positioned transversely 5 cm below the umbilicus . Using the same transducer , we made two ultrasonographic measurements on each participant . The average of the two measurements was used for analysis . The study radiologist , who was blinded to the participants ' treatment status , interpreted all test results . Muscle Strength The study 's physical therapist measured the muscle strength of the participants ' knee flexor and extensor muscles using an isokinetic dynamometer ( Cybex 340 , Lumex , Bay Shore , New York ) . Using a st and ard protocol , we measured peak torque of knee flexion and extension at joint speeds of 90 , 120 , and 180 degrees per second . We measured h and grip strength according to a st and ardized protocol using a grip dynamometer ( Smedley Grip Dynamometer , JA Preston , Jackson , Mississippi ) . The greater of the two measurements was used for analysis . Systemic Endurance To assess systemic endurance , we measured maximal oxygen consumption ( Vo 2 max ) during exercise cycle testing . Upright exercise testing was done using an electronically braked cycle ergometer ( Erich Jaeger , Rockford , Illinois ) . Exercise was initially done unloaded and was then increased by 25 watts every 2 minutes . Participants continued to exercise until they were exhausted or unable to maintain critical pedal frequency ( greater than 50 revolutions per minute ) . During exercise cycle testing , we continuously measured respiratory gas exchange to determine Vo 2 max ( Ergopneumotest , Erich Jaeger ) . Physical Performance The study 's physical therapist used the Physical Performance Test [ 19 ] to assess the participants ' performance on nine physical functions . Participants were asked to write a prescribed sentence , transfer kidney beans using a teaspoon , place a heavy book on a shelf , remove a jacket , pick up a penny from the floor , turn 360 degrees , walk a 50-foot walking test course , and climb stairs to determine speed and the number of flights climbed before the development of fatigue . The test score is based on the time required to complete each task . Higher scores ( the best performance is a maximum score of 36 ) are associated with the shortest time required to complete a task and with better functional status . Cognitive Function and Mood Each participant completed the Trails B Test , the Mini-Mental State Examination , the Digit Symbol Substitution Test , and the Geriatric Depression Scale [ 20 - 23 ] . The Trails B Test ( from the Halstead-Reitan Neuropsychological Test 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 effect of protein supplementation on athletic performance and hormonal changes was examined in 21 experienced collegiate strength/power athletes participating in a 12-week resistance training program . Subjects were r and omly assigned to either a protein supplement ( PR ; n = 11 ) or a placebo ( PL ; n = 10 ) group . During each testing session subjects were assessed for strength ( one repetition maximum [ 1-RM ] bench press and squat ) , power ( Wingate anaerobic power test ) and body composition . Resting blood sample s were analyzed at weeks 0 ( PRE ) , 6 ( MID ) and 12 ( POST ) for total testosterone , cortisol , growth hormone , and IGF-1 . No difference was seen in energy intake between PR and PL ( 3034 ± 209 kcal and 3130 ± 266 kcal , respectively ) , but a significant difference in daily protein intake was seen between PR ( 2.00 g·kg body mass[BM](-1)·d(-1 ) ) and PL ( 1.24 g·kgBM(-1)·d(-1 ) ) . A greater change ( p < 0.05 ) in the ∆ 1-RM squat was seen in PR ( 23.5 ± 13.6 kg ) compared to PL ( 9.1 ± 11.9 kg ) . No other significant strength or power differences were seen between the groups . Cortisol concentrations were significantly lower at MID for PL and this difference was significantly different than PR . No significant changes were noted in resting growth hormone or IGF-1 concentrations in either group . Although protein supplementation appeared to augment lower body strength development , similar upper body strength , anaerobic power and lean tissue changes do not provide clear evidence supporting the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes . Key pointsCollegiate strength/power athletes may not meet daily recommended energy or protein needs . When athletes are provided a protein supplement they appear to meet the recommended daily protein intake for strength/power athletes . Protein supplementation did augment lower body strength development in experienced strength/power athletes .  Results of upper body strength , anaerobic power and lean tissue changes did not support the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes 1 . In adult humans with growth hormone deficiency , treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance . The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone ( 0.07 units/kg at night ) in a double-blind , placebo-controlled trial lasting 6 months . 2 . Compared with placebo , resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone . No differences were noted between the groups with respect to left ventricular end-systolic dimension , fractional shortening , wall thicknesses or mean arterial blood pressure . Left ventricular myocardial mass increased in the group given recombinant human growth hormone . 3 . The supine plasma renin activity was increased and remained elevated over the 6 months , whereas the plasma aldosterone concentration was unchanged , after treatment with recombinant human growth hormone . Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone . 4 . We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency result ed in small increases in left ventricular pre-load , due to the sodium-retaining action of growth hormone . Activation of the renin-aldosterone system was involved in such changes . Myocardial hypertrophy was observed without changes in mean arterial pressure , reflecting the anabolic action of growth hormone Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population 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 OBJECTIVE Adult growth hormone deficiency ( AGHD ) is characterized by abnormalities in body composition and a poor perceived quality of life ( QoL ) . Weight‐based high‐dose growth hormone replacement ( GHR ) results in improvements in body composition and QoL in AGHD . However , a high patient percentage reported side‐effects on high‐dose GHR result ing in a high rate of patient withdrawal from growth hormone ( GH ) treatment . High‐dose GH therapy also leads to supraphysiological serum insulin‐like growth factor‐I ( IGF‐I ) concentrations that have been associated with breast and prostate cancer , raising major concerns over the use of such high‐dose GH regimen in AGHD . The aim of this study was to assess the effects of low‐dose growth hormone replacement ( GHR ) on body composition and QoL as early as 1 and 3 months 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 In overtrained athletes , several signs and symptoms have been associated with the imbalance between training and recovery . However , reliable diagnostic markers for distinguishing between well-trained , overreached ( OR ) and overtrained ( OT ) athletes are lacking . A hallmark feature of overtraining syndrome ( OTS ) is the inability to sustain intense exercise and recover for the next training or competition session . We therefore devised a test protocol utilizing two bouts of maximal work . With this test protocol we tried to establish a difference in hormonal responses between the training status of T and OR athletes . Seven well-trained cyclists participated in this study and were tested before and after a training camp . We also present the data of one OT motocross athlete who was clinical ly diagnosed as overtrained . All athletes performed two maximal exercise tests separated by 4 h. Blood was analyzed for cortisol , adrenocorticotrophic hormone ( ACTH ) , growth hormone and prolactin ( PRL ) . Performance decreased by 6 % between the first and the second exercise test in the OR group and by 11 % in the OT subject . Moreover , during the second exercise test there were more marked differences between the T and OR athletes ; in particular , the OT subject did not show an increase in some of the hormonal responses . PRL increased only by 14 % in the OT subject ’s second test and there was a 7 % decrease in ACTH . The two exercise approach enables us to detect subtle performance decrements that will not be identified by one exercise trigger . The hormonal responses to the second exercise test were different between the T and OR athletes ( the increase in the T group was higher than in the OR that was higher than in the OT ) . The results of the case presentation of an overtrained athlete provide evidence of an altered and dysfunctional hypothalamic – pituitary axis response to two bouts of maximal exercise . These findings can be used to develop markers for diagnosis of OTS and to begin to address the pathologic mechanism operative in the syndrome , as well as providing an outcome measure to evaluate possible therapeutic regimes The aim of the present prospect i ve longitudinal study was to investigate the hormonal response in overtrained athletes at rest and during exercise consisting of a short-term exhaustive endurance test on a cycle ergometer at an intensity 10 % above the individual anaerobic threshold . Over a period of 19+/-1 months , 17 male endurance athletes ( cyclists and triathletes ; age 23.4+/-1.6 yr ; VO2max . 61.2+/-1.8 mL x min(-1 ) x kg(-1 ) ; means+/-SEM ) were examined five times on two separate days under st and ardized conditions . Short-term overtraining states ( OT , N=15 ) were primarily induced by an increase of frequency of high-intensive bouts of exercise or competitions without increase of the total amount of training . OT was compared with normal training states intraindividually ( NS , N=62 ) . During OT , the time to exhaustion of the exercise test was significantly decreased by 27 % on average . At rest and during exercise , the concentrations in plasma and the nocturnal excretion in urine of free epinephrine and norepinephrine were not significantly changed during OT . At physical rest , the concentrations of ( free ) testosterone , cortisol , luteinizing hormone , follicle-stimulating hormone , adrenocorticotropic hormone , growth hormone , and insulin during OT were comparable with those during NS . A significantly ( P < 0.025 ) lower maximal exercise-induced increase of the adrenocorticotropic hormone and growth hormone , as well as a trend for a decrease of cortisol ( P=0.060 ) and insulin ( P=0.036 ) , was measured . The response of free catecholamines as well as the ergometric performance of an all-out 30-s test was unchanged . Serum urea , uric acid , ferritin , and activity of creatine kinase showed no differences between conditions . In conclusion , the results confirm the hypothesis of a hypothalamo-pituitary dysregulation during OT expressed by an impaired response of pituitary hormones to exhaustive short-endurance exercise OBJECTIVE To determine whether in children born small for gestational age ( SGA ) high-dose growth hormone ( GH ) treatment is not only associated with catch-up of growth and with gain of lean mass , but also with a more central fat distribution . STUDY DESIGN Short children who were SGA ( n = 25 ; age [ mean + /- SD ] , 5.3 + /- 1.5 years ) were r and omly assigned to remain untreated ( n = 14 ) or to receive GH ( n = 11 ; sc 66 mug/Kg/d ) . Growth status and body composition were assessed at the study 's start , after 1 year , and after 2 years with anthropometry and absorptiometry . RESULTS Children who were treated with GH gained more height and weight than children who were untreated and developed a less adipose body composition ( all P < .0001 ) , as expected . However , these changes were also accompanied by a relatively more centripetal distribution of fat mass ( 0 - 2 year change in ratio of trunk fat to limb fat ; 0.26 + /- 0.23 versus 0.02 + /- 0.15 ; P < .0001 ) . CONCLUSION In children who are SGA , catch-up growth induced by exogenous GH in high doses is accompanied by a less adipose body composition and a more central fat distribution 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 We have compared the growth and the body composition in children with Prader‐Willi syndrome ( PWS ) with and without growth hormone treatment ( recombinant GH 0.1 IU/kg/day ) after a 1‐y period . Twenty‐nine prepubertal children with PWS , with mean body mass index ( BMI ) SDS of 2.2 , and 10 ( control ) healthy obese children with mean BMI SDS of 5.6 , underwent 24‐h frequent blood sampling . Both PWS and control obese children had low and similar GH levels ( 0.7 /ng/l ± 0.4 SD ) . Serum IGF‐I levels , however , were significantly lower in children with PWS ( ‐1.5 SDS ± 0.8 SD vs ‐0.2 SDS ±0.8 SD ) . The 29 PWS children were r and omized into 2 groups of 15 and 14 subjects for GH treatment and no treatment  , respectively . Height velocity increased from ‐1.9 SDS to + 6.0 SDS in the treated group ( p < 0:001 ) and decreased from ‐0.1 SDS to ‐1.4 SDS in the control PWS group during the study year . BMI decreased significantly for the treated group ( + 3.0 SDS to + 2.0 SDS ) . Relative fat mass decreased significantly , while fat‐free mass increased ( p < 0:001 ) for the treated group . No significant changes were noticed in body composition in the control PWS group . In conclusion , the low spontaneous 24‐h GH secretion , regardless of body weight , and the exceptional response to growth hormone treatment together with the finding of low IGF‐I levels suggest that growth hormone deficiency is a common feature of PWS , as a result of hypothalamic dysfunction . Treatment with growth hormone is beneficial for the majority of PWS children BACKGROUND Short stature and ovarian failure are characteristic features of Turner 's syndrome . Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome , a r and omized , placebo-controlled trial is needed to document whether such treatment increases adult height . Furthermore , it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit . We examined the independent and combined effects of growth hormone and early , ultra-low-dose estrogen on adult height in girls with Turner 's syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 149 girls , 5.0 to 12.5 years of age , to four groups : double placebo ( placebo injection plus childhood oral placebo , 39 patients ) , estrogen alone ( placebo injection plus childhood oral low-dose estrogen , 40 ) , growth hormone alone ( growth hormone injection plus childhood oral placebo , 35 ) , and growth hormone-estrogen ( growth hormone injection plus childhood oral low-dose estrogen , 35 ) . The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week . The doses of ethinyl estradiol ( or placebo ) were adjusted for chronologic age and pubertal status . At the first visit after the age of 12.0 years , patients in all treatment groups received escalating doses of ethinyl estradiol . Growth hormone injections were terminated when adult height was reached . RESULTS The mean st and ard-deviation scores for adult height , attained at an average age of 17.0±1.0 years , after an average study period of 7.2±2.5 years were -2.81±0.85 , -3.39±0.74 , -2.29±1.10 , and -2.10±1.02 for the double-placebo , estrogen-alone , growth hormone-alone , and growth hormone-estrogen groups , respectively ( P<0.001 ) . The overall effect of growth hormone treatment ( vs. placebo  ) on adult height was a 0.78±0.13 increase in the height st and ard-deviation score ( 5.0 cm ) ( P<0.001 ) ; adult height was greater in the growth hormone-estrogen group than in the growth hormone-alone group , by 0.32±0.17 st and ard-deviation score ( 2.1 cm ) ( P=0.059 ) , suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone . CONCLUSIONS Our study shows that growth hormone treatment increases adult height in patients with Turner 's syndrome . In addition , the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement . ( Funded by the National Institute of Child Health and Human Development and Eli Lilly ; Clinical Trials.gov number , NCT00001221 . ) Objective To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn . Summary Background Data The hypermetabolic response to severe burn is associated with increased energy expenditure , insulin resistance , immunodeficiency , and whole body catabolism that persists for months after injury . Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses . Methods Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone ( 0.05 mg/kg per day ) on muscle accretion and bone growth . Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn . Total body weight , height , dual-energy x-ray absorptiometry , indirect calorimetry , and hormone values were measured at discharge , then at 6 months , 9 months , and 12 months after burn . Results were compared between groups . Results Growth hormone subjects gained more weight than placebo subjects at the 9-month study point ; this disparity in weight gain continued to exp and throughout the remainder of the study . Height also increased in the growth hormone group compared with controls at 12 months . Change in lean body mass was greater in those treated with growth hormone at 6 , 9 , and 12 months . Bone mineral content was increased at 9 and 12 months ; this was associated with higher parathormone levels . Conclusions Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn Objective The purpose of this study was to initially determine if growth hormone or nutrients , given alone or together , could enhance absorption from the remnant small bowel after massive intestinal resection . If clinical improvement were observed , this therapy would then be used to treat patients with the short-bowel syndrome over the long term . Summary Background Data Patients who undergo extensive resection of the gastrointestinal tract frequently develop malabsorption and require long-term parenteral nutrition . The authors hypothesized that the administration of growth factors and /or nutrients could enhance further compensation of the remnant intestine and thereby improve absorption . Specifically , animal studies have shown that there is enhanced cellularity with the administration of growth hormone ( GH ) or glutamine ( GLN ) , or a fiber-containing diet . Methods Initially , 17 studies were performed in 15 total parenteral nutrition (TPN)-dependent short-bowel patients over 3 to 4 weeks in the clinical research center ; the first week served as a control period , and during the next 1 to 3 weeks , the specific treatment was administered and evaluated . Throughout the study , food of known composition was provided and all stool was collected and analyzed to determine absorption across the remaining bowel . The effect of a high-carbohydrate , low-fat diet ( DIET ) , the amino acid glutamine ( GLN ) and growth hormone ( GH ) administered alone or in combination with the other therapies ( GH + GLN + DIET ) was evaluated . The treatment was exp and ed to 47 adults ( 25 men , 22 women ) with the short-bowel syndrome , dependent on TPN for 6 ± 1 years . The average age was 46 ± 2 years , and the average jejunal-ileal length was 50 ± 7 cm ( median 35 cm ) in those with all or a portion of colon and 102 ± 24 cm ( median 102 cm ) in those with no colon . After 28 days of therapy , the patients were discharged on only GLN + DIET . Results The initial balance studies indicated improvement in absorption of protein by 39 % accompanied by a 33 % decrease in stool output  with the GH + GLN + DIET . In the long-term study , 40 % of the group remain off TPN and an additional 40 % have reduced their TPN requirements , with follow-up averaging a year and the longest being over 5 years The hypothesis that an increase in ambient temperature modulates neuroendocrine response in clinical ly used provocative pituitary function tests was verified . Healthy male volunteers were subjected to insulin tolerance tests in two r and omized trials . In the first trial hypoglycemia was induced by a bolus injection of insulin ( 0.1 U per kg of BW , iv ) at room temperature . In the second trial , the subjects were exposed to increased ambient temperature for 45 min before insulin injection and for 45 min thereafter . The environmental temperature was selected to increase body temperature less than 1C . Under conditions of increased temperature basal hormone levels as measured in antecubital venous blood sample s failed to be modified and the hypoglycemia was less severe . Nevertheless , the responses of most ( β-endorphin , ACTH , prolactin , catecholamines ) , but not all ( growth hormone , Cortisol ) , hormones to hypoglycemia were exaggerated . The remarkable increase in ACTH and β-endorphin release was not accompanied by concomitant increase of plasma Cortisol response . The sympathetic-adrenomedullary system was significantly activated , which was manifested particularly by enhanced norepinephrine release . Growth hormone response to hypoglycemia was not modified , while that of prolactin was enhanced . Thus during evaluation of neuroendocrine function under clinical conditions , changes in ambient and body temperature should not be underestimated 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 OBJECTIVE To determine the safety and efficacy of recombinant human growth hormone ( rhGH ) in the treatment of children who are severely burned . SUMMARY BACKGROUND DATA During the last decade , we have used recombinant human growth hormone ( rhGH ; 0.2 mg/kg/day s.q . ) to successfully treat 130 children with more than 40 % total body surface area ( TBSA ) burns to enhance wound healing and decrease protein loss . A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH  has recently been reported in two large European trials which questions the therapeutic safety of rhGH . METHODS The records of 263 children who were burned were review ed . Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a r and omized clinical trial ( n = 48 ) or therapeutically ( n = 82 ) were compared with r and omized placebo-administered controls ( n = 54 ) , contiguous matched controls ( n = 48 ) , and matched patients admitted after August 1997 , after which no patients were treated with rhGH ( n = 31 ) . Morbidity and mortality , which might be altered by rhGH therapy , were considered with specific attention to organ function or failure , infection , hemodynamics , and calcium , phosphorous , and albumin balance . RESULTS A 2 % mortality was observed in both rhGH and saline placebo groups in the controlled studies , with no differences in septic complications , organ dysfunction , or heart rate pressure product identified . In addition , no difference in mortality could be shown for those given rhGH therapeutically versus their controls . No patient deaths were attributed to rhGH in autopsies review ed by observers blinded to treatment . Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients , whereas exogenous albumin requirements and the development of hypocalcemia was reduced . CONCLUSIONS Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious Objective To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching ( NFOR ) . Design A prospect i ve case-control study using a monthly performance monitor with a st and ardised field test to detect the performance changes . Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones . Setting Sporting field and sports medical laboratory . Participants Ninety-four young elite soccer players were monitored during the 2006–2008 seasons . Twenty-one players were invited to the laboratory , seven of whom showed a significant performance decrease . Main outcome measures Performance change over time , scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone ( ACTH ) , growth hormone ( GH ) and cortisol . Results Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching . Scores were higher on depression and anger , whereas the resting GH levels and ACTH levels after maximal exercise were reduced . ACTH and GH were capable of classifying all but one player correctly as either NFOR or control . Conclusions Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR . Performance , mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players The hypothesis of a gamma-aminobutyric acid ( GABA ) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed . As GABA has been shown to affect basal growth hormone ( GH ) secretion in humans , the assessment of plasma GH response to a GABAergic drug , such as sodium valproate ( SV ) , in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness . For this purpose , we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls , and measured plasma GH levels before and after the drug administration . SV enhanced basal GH secretion in healthy male volunteers , but not in chronic schizophrenics . These results suggest a defect of the endogenous GABA system in chronic schizophrenia . Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown The aim of this study was to compare the acute hormonal responses following two different eccentric exercise velocities .  Seventeen healthy , untrained , young women were r and omly placed into two groups to perform five sets of six maximal isokinetic eccentric actions at slow ( 30 ° s−1 ) and fast ( 210 ° s−1 ) velocities with 60‐s rest between sets . Growth hormone , cortisol , free and total testosterone were assessed by blood sample s collected at baseline , immediately postexercise , 5 , 15 and 30 min following eccentric exercise .  Changes in hormonal responses over time were compared between groups , using a mixed model followed by a Tukey 's post hoc test . The main findings of the present study were that the slow group showed higher growth hormone values immediately ( 5·08 ± 2·85 ng ml−1 , P = 0·011 ) , 5 ( 5·54 ± 3·01 ng ml−1 , P = 0·004 ) and 15 min ( 4·30 ± 2·87 ng ml−1 , P = 0·021 ) posteccentric exercise compared with the fast group ( 1·39 ± 2·41 ng ml−1 , 1·34 ± 1·97 ng ml−1 and 1·24 ± 1·87 ng ml−1 , respectively ) , and other hormonal responses were not different between groups ( P>0·05 ) . In conclusion , slow eccentric exercise velocity enhances more the growth hormone(GH ) response than fast eccentric exercise velocity without cortisol and testosterone increases The gene product from the ob gene , leptin , has recently been characterized in humans . The circulating level of leptin is related to body mass index ( BMI ) and more closely to estimates of total body fat , whereas visceral fat has been reported to be of minor importance . However , it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition . We studied leptin in adult growth hormone (GH)-deficient ( GHD ) patients substituted with GH treatment for 12 months in a parallel double-blind , placebo-controlled study . Twenty-seven GHD adults aged 44.9 + /- 1.9 years underwent  anthropometric measurements  for determination of regional and total body fat ( BMI , waist to hip ratio [ WHR ] , computed tomographic [ CT ] scan , dual-energy x-ray absorptiometry [ DEXA ] scan , and bioimpedance analysis [ BIA ] ) before and after 12 months of placebo-controlled GH substitution ( 2 IU/m2 ) in a parallel design . The same measurements were performed in 42 healthy adults aged 39.1 + /- 1.7 years . The logarithm of serum leptin levels correlated positively with abdominal subcutaneous fat and total body fat ( BIA and DEXA ) in untreated GHD patients and healthy subjects . Fasting insulin did not correlate with leptin levels in either of the groups . After 12 months of GH administration , the body composition of GHD patients was significantly changed with respect to a marked decrease in body fat . The relations of leptin to the estimates of body fat were maintained , and leptin was furthermore related to BMI and fasting insulin . In multiple linear regression analyses , additional estimates of visceral adiposity ( intraabdominal fat and maximal anterior-posterior diameter determined by CT scan ) were significant determinants of leptin in the healthy subjects . The increase in fasting insulin levels during GH substitution correlated negatively with the reduction in leptin levels ( r = -.823 , P = .003 ) . At baseline , leptin levels were increased in the patients compared with controls in both sexes ( women , 21.8 + /- 3.3 v 11.3 + /- 1.4 ng/mL , P = .002 ; men , 8.1 + /- 1.2 v 4.7 + /- 0.7 ng/mL , P = .008 ) . Leptin levels were similar in GHD patients treated for 12 months compared with healthy controls for both women and men ( women , 15.9 + /- 2.3 and 11.3 + /- 1.4 ng/mL , P = .163 ; men , 7.1 + /- 2.8 and 4.7 + /- 0.7 ng/mL , P = .759 ) . In healthy adults and in GHD patients , leptin levels were significantly higher in women than in men ( 11.3 + /- 1.4 v 4.7 + /- 0.7 ng/mL , P < .001 ; 21.8 + /- 3.3 v 8.1 + /- 1.2 ng/mL , P < .001 ) . Gender remained a significant determinant of leptin levels in several models of multiple linear regression analysis also including age , estradiol levels , insulin , and estimates of body fat . We conclude that leptin is increased but not differently regulated in GHD patients compared with normal subjects , and that leptin levels are closely related to estimates of body fat . This relationship is maintained during a decrease in body fat due to GH substitution It has been reported that exercise under hypoxic conditions elevates acute growth hormone secretion after exercise compared with that under normoxic conditions . This study examined the influence of resistance training under moderate hypoxic conditions on muscle thickness , strength and hormonal responses . Thirteen healthy men were assigned into two groups matched for physical fitness level and then r and omized into two groups that performed exercise under normoxic ( FiO2 = 20·9 % ) or hypoxic ( FiO2 = 12·7 % ) conditions . Three sets of elbow extensions with unilateral arm were performed to exhaustion at a workload of a 10 repetition maximum with 1‐minute intervals for 3 days per week for 8 weeks . The thickness of the biceps and triceps brachii was determined using B‐mode ultrasound before and after training . Blood sampling was carried out before and after exercise , as well as during the first and last training sessions . Increase in the thickness of the triceps brachii in trained arm was significantly greater in the hypoxic group than in the normoxic group . The 10 repetition maximum was significantly increased not only in the trained arm but also in the untrained arm in both groups . Serum growth hormone concentrations after exercise were significantly higher in the hypoxic group than in the normoxic group on both the first and last training sessions . These findings suggest that hypoxic resistance training elicits more muscle hypertrophy associated with a higher growth hormone secretion , but that the greater muscle hypertrophy did not necessarily contribute a greater gain of muscle strength BACKGROUND A previous controlled study of ten patients with short bowel syndrome ( SBS ) reported human recombinant growth hormone result ed in a significant increase in body weight and lean body mass ( LBM ) without clinical edema . The aim of this study was to assess the effect of growth hormone , glutamine , and diet on body composition . METHODS A r and omized , 6-week , double-blind , placebo-controlled , crossover study was performed in eight patients . Active treatment was 21 days of growth hormone , oral glutamine , and a high-carbohydrate-low-fat ( HCLF ) diet .  Body composition was determined by dual-energy x-ray absorptiometry ( DEXA ) scan . Treatments were compared by paired t test . RESULTS Active treatment result ed in significant increases in body weight ( mean 3.02 + /- 0.7 kg , p < .05 ) and lean body mass , ( mean 3.96 + /- 0.5 kg , p < .001 ) . Percent body fat was significantly reduced in the actively treated group ( mean -2.51 % + /- 0.4 , p < .001 ) . Body weight returned to base-line within 2 weeks of discontinuing active treatment . Macronutrient and fluid absorption did not increase with active treatment . CONCLUSIONS Treatment with growth hormone , glutamine , and HCLF diet result ed in decreased percent body fat and increased body weight and LBM in patients with SBS , without an increase in macronutrient or fluid absorption . The positive findings are most likely a reflection of increased extracellular fluid because all eight patients developed peripheral edema on active treatment . Furthermore , the positive effect of active treatment does not appear to be sustained once discontinued BACKGROUND Menopause is associated with decreases in lean mass and increases in fat mass . Serum hormone levels and hormone replacement therapy ( HRT ) may modify the effects of exercise training on body composition in postmenopausal women . METHODS We assessed the changes in total body and regional lean soft tissue and fat mass ( using dual-energy x-ray absorptiometry ) in 94 sedentary postmenopausal women , aged 40 - 65 years , after 12 months of resistance and weight-bearing aerobic exercise training . Women currently on oral HRT ( n = 39 ) and not on HRT ( n = 55 ) were r and omized within groups to exercise and no exercise , result ing in four groups : exercise + HRT ( n = 20 ) , HRT ( n = 22 ) , exercise ( n = 24 ) , and control ( n = 28 ) . Fasting blood sample s were measured for resting serum total levels of estrone , estradiol , cortisol , and rostenedione , growth hormone , and insulin-like growth factor 1 at baseline and 12 months . RESULTS We found significant effects of exercise on increases in total body , arm , and leg lean soft tissue mass , and decreases in leg fat mass and percentage of body fat . There were no interaction effects of exercise and HRT on the changes in muscle strength and body composition . No significant changes in total hormone levels were found after 12 months . CONCLUSIONS Exercise training result ed in significant beneficial changes in lean soft tissue and fat mass in early postmenopausal women . These changes in body composition were neither influenced by prolonged HRT use nor accompanied by changes in total levels of the hormones determined in this study 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 BACKGROUND A blunted growth hormone and prolactin response to pharmacological stress test have previously been found in depressed patients , as well as an increased cortisol response to psychosocial stress . This study investigated these hormones in response to acute exercise using an incremental bicycle test . METHOD A cross-sectional comparison of cortisol , growth hormone , and prolactin in depressed ( n=137 ) and healthy ( n=44 ) subjects during rest and in response to an incremental bicycle test . Secondly , we tested the depressed patients again after a 4-month r and omized naturalistic exercise intervention . RESULTS Resting plasma levels of growth hormone ( GH ) , cortisol , or prolactin ( PRL ) did not differ between depressed and healthy subjects ( all p-values>.12 ) . In response to an incremental bicycle test the GH ( p=.02 ) and cortisol ( p=.05 ) response in depressed was different compared to healthy controls . The effect of acute exercise stress on PRL ( p=.56 ) did not differ between depressed and healthy subjects . Apart from a decrease in GH response in the strength-training group ( p=.03 ) the pragmatic exercise intervention did not affect resting hormonal levels , or the response to acute exercise . CONCLUSIONS Patients with mild to moderate depression had a different growth hormone and cortisol response to acute exercise stress compared to healthy controls . Strength training was able to reduce the growth hormone response to acute exercise stress in this patient population . Studies with more rigorous inclusion criteria and higher exercise frequencies are needed to evaluate and confirm the possible effect of exercise in depressed subjects 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 OBJECTIVE To evaluate the effect of severe head injury on both the secretion of basal pituitary hormones and the response to exogenous synthetic hypothalamic releasing factors administration . DESIGN Prospect i ve , clinical study . SETTING General intensive care unit in a university teaching hospital , Italy . PATIENTS Comatose , head-injured patients ( n = 22 ) , all intubated and mechanically ventilated , invasively monitored without previous endocrinologic problems and substitutive therapies . INTERVENTIONS Routine neuroemergency procedures ; administration of exogenous , synthetic hypothalamic releasing hormones . MEASUREMENTS AND MAIN RESULTS Determinations of basal concentrations of growth hormone ( GH ) , prolactin ( PRL ) , thyroid-stimulating hormone ( TSH ) , triiodothyronine , and thyroxine were performed daily in the first week and on days 15 and 16 after the trauma . Plasma insulin-like growth factor-I and cortisol were also determined on days 2 , 7 , and 15 . We carried out a thyrotropin-releasing hormone ( TRH ) test for the evaluation of the PRL , TSH , and GH responses on days 1 and 16 after the trauma and a growth hormone-releasing hormone ( GHRH ) test for the evaluation of GH and PRL responses on days 2 , 7 , and 15 after the trauma . Outcome was evaluated at 6 mos with the GOS . Triiodothyronine showed low values , even if in the normal range ; thyroxine remained in the normal range . Significant increases in insulin-like growth factor-I concentrations were observed on both days 7 and 15 compared with day 2 ( p = .024 and p = .034 , respectively ) . The GH response to GHRH was significantly greater on days 7 and 15 than in the very acute phase ( p < .01 comparing days 7 and 15 vs. day 2 ) . We found a higher GH response to GHRH on day 7 in group 1 vs. group 2 ( as both peak and area under the curve , p = .018 and p = .015 , respectively ) . No difference in GH response was detected on days 2 and 15 . A " paradoxical " response of GH to TRH was observed on the day after the head trauma ( basal vs. peak , p = .002 ) but not on day 16 . The GH peak response to TRH was greater on day 1 in those patients with an unfavorable course ( group 1 vs. group 2 , p < .05 ) . The TSH response to TRH was not significantly correlated to the severity of trauma , but it was significantly ( p < .04 ) higher in group 1 than in group 2 . Finally , a " paradoxical " PRL response to GHRH administration was present on day 2 ( basal vs. peak , p=.0003 ) , day 7 ( basal vs. peak , p = .01 ) , and on day 15 after the trauma ( basal vs. peak , p = .04 ) . CONCLUSIONS Some of the responses to provocative tests have been identified as " paradoxical " and seem to have a great importance in the definition of prognosis in severe head-injured patients , specifically the GH response to TRH and the PRL response to GHRH  that are significantly correlated with outcome The aim of this prospect i ve , longitudinal , controlled study is to describe the long-term safety and efficacy of growth hormone ( GH ) administration on craniofacial morphology in boys with short stature . Forty-six boys , who started GH treatment at the Department of Paediatrics Göteborg Paediatric Growth Research Centre , were consecutively included in the study . Twenty-five boys were classified as growth hormone-deficient ( GHD ) and 21 as idiopathic short stature ( ISS ) . The patients were injected with 33 ( n=31 ) or 67 ( n=15 ) microg GH/kg body weight/day . The mean age at the start of treatment was 11.8 years [ st and ard deviation ( SD ) 1.7 ] . To assess craniofacial growth , st and ard lateral cephalometric radiographs were obtained at the start of GH treatment , annually during 4 years , and at the end of GH treatment or when growth was less than 1 cm/year . The mean follow-up period was 6.4 years ( SD 1.4 ) . Growth changes were compared with boys from a semi-longitudinal reference group of 130 healthy subjects , 7 - 21 years of age . t-tests for independent and paired sample s and multiple regression analysis were applied . Age- and gender-specific st and ard deviation scores for the cephalometric variables were calculated . Repeated measures analysis of variance was used to identify significant covariates over time , such as low/high GH dose and GHD/ISS and orthodontic treatment . During the study period , eight ( out of 40 ) boys were treated with fixed orthodontic appliances , three with functional appliances ( activators ) , and three with other appliances ( plates and lingual arches ) . During GH treatment period , an overall enhancement in growth of the facial skeleton was observed in boys with short stature . The changes induced by GH yielded a more prognathic growth pattern , a more anterior position of the jaws in relation to the cranial base , and increased anterior rotation of the m and ible . The m and ibular corpus length and anterior face height of the GH-treated boys were greater at the end of the study compared with the boys in the reference group . No differences in growth response were noted either between the GHD and ISS boys or between those treated with either 33 ( low dose ) or 67 ( high dose ) microg GH/kg body weight/day . The only change that remained significantly correlated with orthodontic treatment was the alteration in m and ibular ramus height , showing a larger change in the boys who had not undergone orthodontic therapy . The findings of this study demonstrate that GH treatment has a favourable influence on the craniofacial growth pattern of boys with short stature without acromegalic features BACKGROUND Leptin , ghrelin , and insulin are hormonal regulators of energy balance and , therefore , may be related to growth during infancy . Zinc is essential for growth , and its growth effects may be mediated through these hormones . OBJECTIVE We examined the effects of supplemental zinc on plasma leptin , ghrelin , and insulin concentrations among young children at risk of zinc deficiency and examined the relations between these hormones and physical growth . DESIGN Children ( n = 142 ) aged 6 - 8 mo were r and omly assigned to receive 3 mg Zn/d as a supplement , in a fortified food , or as a placebo for 6 mo . Relations between hormones and anthropometric z scores , body composition , and growth rates were examined at baseline and 3 and 6 mo after the start of the intervention . RESULTS No treatment group-related differences were found in plasma leptin , ghrelin , or glucose concentrations or in anthropometric z scores at 3 or 6 mo after the start of the zinc intervention . Neither plasma leptin nor ghrelin concentrations at baseline or 3 mo were predictive of subsequent changes in growth . However , changes in weight-for-age z scores over the two 3-mo time intervals were positively associated with subsequent leptin concentrations and inversely associated with subsequent plasma ghrelin concentrations . CONCLUSIONS Supplemental zinc did not affect the children 's  growth , anthropometric indexes , or plasma hormone concentrations in this study population . Our results suggest that plasma leptin and ghrelin concentrations in later infancy are a consequence of previous weight changes rather than predictors of short-term growth The use of ergogenic nutritional supplements is becoming inseparable from competitive sports . β-Hydroxy-β-Methylbutyric acid ( HMB ) has recently been suggested to promote fat-free mass ( FFM ) and strength gains during resistance training in adults . In this prospect i ve r and omized , double-blind , placebo-controlled study , we studied the effect of HMB ( 3 g/day ) supplementation on body composition , muscle strength , anaerobic and aerobic capacity , anabolic/catabolic hormones and inflammatory mediators in elite , national team level adolescent volleyball players ( 13.5–18 years , 14 males , 14 females , Tanner stage 4–5 ) during the first 7 weeks of the training season .  HMB led to a significant greater increase in FFM by skinfold thickness ( 56.4 ± 10.2 to 56.3 ± 8.6 vs. 59.3 ± 11.3 to 61.6 ± 11.3 kg in the control and HMB group , respectively , p < 0.001 ) . HMB led to a significant greater increase in both dominant and non-dominant knee flexion isokinetic force/FFM , measured at fast ( 180 ° /sec ) and slow ( 60 ° /sec ) angle speeds , but had no significant effect on knee extension and elbow flexion and extension . HMB led to a significant greater increase in peak and mean anaerobic power determined by the Wingate anaerobic test ( peak power : 15.5 ± 1.6 to 16.2 ± 1.2 vs. 15.4 ± 1.6 to 17.2 ± 1.2 watts/FFM , mean power : 10.6 ± 0.9 to 10.8 ± 1.1 vs. 10.7 ± 0.8 to 11.8 ± 1.0 watts/FFM in control and HMB group , respectively , p < 0.01 ) , with no effect on fatigue index  . HMB had no significant effect on aerobic fitness or on anabolic ( growth hormone , IGF-I , testosterone ) , catabolic ( cortisol ) and inflammatory mediators ( IL-6 and IL-1 receptor antagonist ) . HMB supplementation was associated with greater increases in muscle mass , muscle strength and anaerobic properties with no effect on aerobic capacity suggesting some advantage for its use in elite adolescent volleyball players during the initial phases of the training season . These effects were not accompanied by hormonal and inflammatory mediator changes BACKGROUND Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid , electrolytes , and other nutrients . Although the remaining bowel undergoes morphological and functional adaptation , often these changes are inadequate to support the individual by enteral feedings , and parenteral nutrition is required to prevent dehydration , electrolyte disturbances , and malnutrition . Substances such as growth hormone , glutamine , and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption . This study was undertaken to determine whether the co-administration of exogenous growth hormone , supplemental glutamine , and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection . METHODS Ten patients ( 5 men , 5 women , aged 43 + /- 4 years ) with short bowel syndrome were studied 6 + /- 1 years after surgical resection . All patients were admitted to the Clinical Research Center for a 28-day period ; the first week served as a control period when nutritional ( enteral and parenteral ) and medical management simulated usual home therapy . Thereafter , eight patients received exogenous growth hormone , supplemental glutamine , and a modified high-carbohydrate , high-fiber diet . Two patients were treated with the modified diet alone . The efficiency of net nutrient absorption ( percent absorbed ) for total calories , protein , fat , carbohydrate , water , and sodium was calculated from the measured nutrient intake and stool losses . RESULTS Three weeks of treatment with growth hormone , glutamine , and a modified diet increased total caloric absorption from 60.1 + /- 6.0 % to 74.3 + /- 5.0 % ( p < or = .003 ) , protein absorption from 48.8 + /- 4.8 % to 63.0 + /- 5.4 % ( p < or = .006 ) , and carbohydrate absorption from 60.0 + /- 9.8 % to 81.5 + /- 5.3 % ( p < or = .02 ) . Fat absorption did not change ( 61.0 + /- 5.3 % to 60.3 + /- 7.9 % , p = NS ) . Water and sodium absorption increased from 45.7 + /- 6.7 % to 65.0 + /- 7.3 % ( p < or = .002 ) and from 49.0 + /- 9.8 % to 69.6 + /- 6.5 % ( p < or = .04 ) , respectively . These absorptive changes result ed in a decrease in stool output ( 1,783 + /- 414 g/d control period vs 1,308 + /- 404 g/d third week of treatment , p < or = .05 ) . Treatment with diet alone did not influence nutrient absorption or stool output . CONCLUSIONS The combined administration of growth hormone , glutamine , and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection . These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients . This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome A double-blind , placebo-controlled , crossover study on the effects of 4 months ' growth hormone ( GH ) treatment was carried out in 22 GH-deficient adults ( 8 women , 14 men ; mean [ SEM ] age 23.8 [ 1.2 ] years ) . 1 patient was withdrawn because of oedema . Mean total body weight of the other 21 did not change , whereas mean muscle volume of the thigh , estimated by computerised tomography ( CT ) , was significantly higher after GH than after placebo ( 70.0 [ 3.7 ] vs 66.3 [ 3.1 ] ml/0.8 cm cross-sectional slice ) . The mean adipose tissue volume of the thigh and subscapular skinfold thickness fell significantly during GH treatment . Growth hormone caused a small increase in the isometric strength of the quadriceps muscles and a significant rise in exercise capacity ( 60.8 [ 7.2 ] vs 54.2 [ 6.6 ] kJ ) . The heart rate both at rest and after maximum exercise was low during the placebo period and increased significantly during GH treatment . Blood pressure and echocardiographic wall mass of the left ventricle did not change during the study . Growth hormone increased both mean glomerular filtration rate and renal plasma flow from a subnormal level on placebo to a level comparable with that of an age-matched control group . The filtration fraction did not change . Urinary albumin excretion was in the low normal range and was not affected by GH treatment . Finally , GH treatment normalised mean circulating levels of insulin-like growth factor 1 ( IGF-1 ) , which were low after the placebo period ( 96 [ 9 ] micrograms/l placebo ; 224 [ 28 ] micrograms/l GH ) . These findings suggest that GH , in a conventional replacement dose , has several potentially beneficial effects in GH-deficient adults and therefore encourage future long-term trials Summary The dose-effect relationship of an i.v . bolus of synthetic h-GRF-44 on growth-hormone and prolactin secretion has been studied . Seven healthy adult volunteers received in a r and om order h-GRF-44 2.5 , 5 , 10 , 20 , 40 and 80 µg and a placebo . Plasma growth hormone ( GH ) was determined between 30 min before and 240 min after injection , the area under the curve ( AUC ) and the peak GH level being used to assess the response . For both parameters a dose-effect relationship was observed . Doses as low as 2.5 µg were capable of eliciting a rise in GH plasma levels in few patients . Above 40 µg the dose-effect curves tended to plateau , although the decrease in the slope of the dose-effect curve at the peak was more marked . Intersubject variability was large , so precise determination of the minimal effective dose as well as the lowest dose giving a maximal effect was not possible . The available evidence suggests that the i.v . dose of synthetic h-GRF-44 ( SR 95228 ) which is likely to promote GH release into the blood stream in most healthy adults is within the range 40–100 µg . In these healthy adults unwanted effects were infrequent with these low doses . Unlike previous experience with higher doses of another synthetic h-GRF-44  , prolactin secretion in this study was not affected The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes . In a r and omised order , 11 male judokas ( age : 20.45 ± 0.51 ; height : 1.71 ± 0.3 m ; and body weight : 75.9 ± 3.1 kg ) participate in this study during a period of weight maintenance ( baseline ) and after 7 days of caloric restriction ( CR ) . All subjects performed the Special Judo Fitness Test ( SJFT ) during the two conditions . Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction ( −5~6 MJ/day ) . Our results showed that CR result ed in significant decreases in body weight ( P < 0.05 ) and performance ( P < 0.05 ) . However , heart rate and SJFT index ( P < 0.05 ) increase significantly during CR in comparison to baseline . Moreover , exercise leads to a significant increase in testosterone , cortisol , growth hormone ( GH ) , leukocytes , neutrophils , TNF-α , and IL-6 , in both CR and baseline conditions . Compared to baseline , TNF-α and IL-6 were significantly higher during CR condition ( P < 0.05 ) . Additionally , CR leads to an increase in cortisol and GH ( P < 0.05 ) and a decrease in testosterone concentrations ( P < 0.05 ) OBJECTIVE Impaired systemic hormonal activity caused by hypothalamic and pituitary injury may contribute to neuropsychologic disturbances and poor quality of life after aneurysmal subarachnoid hemorrhage ( SAH ) . This prospect i ve study was design ed to longitudinally evaluate long-term clinical outcome and pituitary function after SAH using dynamic tests for adrencorticotropic and somatotropic secretory capacity . METHODS Endocrine function was assessed by basal hormonal concentrations at 6 - 12 months and 12 - 24 months after SAH . At the 12 - 24 months follow-up , dynamic provocative evaluation of adrenocorticotropic hormone ( ACTH ) and  growth hormone ( GH ) was performed using the insulin tolerance test ( ITT ) . In patients where ITT was contraindicated , an ACTH stimulation test was used to assess ACTH capacity , and a growth hormone releasing hormone (GHRH)-arginine stimulation test was used to assess GH capacity . RESULTS Of 60 patients with SAH screened , 51 were included in the study , and 44 remained to be tested at the two follow-up visits . As assessed by basal hormone concentrations alone , the prevalence of pituitary dysfunction was 34 % at 6 - 12 months and 41 % at 12 - 24 months . When using dynamic tests ( 12 - 24 months ) , impaired pituitary function was detected in 43 % . The ITT detected more cases of central hypoadrenalism and GH deficiency compared with the ACTH- and GHRH-arginine-stimulation tests , respectively . CONCLUSIONS Application of dynamic endocrine tests revealed a high frequency of long-term hypothalamic-pituitary dysfunction after aneurysmal SAH . The role of pituitary dysfunction in the recovery after SAH merits further evaluation
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 .