title: Treatment with human growth hormone in patients with Prader-Labhart-Willi syndrome reduces body fat and increases muscle mass and physical performance Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men. Effect of growth hormone and resistance exercise on muscle growth in young men. Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men. Physical Effects of Short-Term Recombinant Human Growth Hormone Administration in Abstinent Steroid Dependency Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure. The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group.
abstract: Twelve children with documented Prader-Labhart-Willi syndrome were treated with human growth hormone ( 24 U/m2/week ) during 1 year . The children were divided into three groups : group 1 : overweight and prepubertal ( n = 6 , age 3.8–7.0 years ) ; group 2 : underweight and prepubertal ( n = 3 , age 0.6–4.1 years ) ; group 3 : pubertal ( n = 3 , age 9.2–14.6 years ) . In group 1 , height increased from -1.7 SD to -0.6 SD , while weight decreased from 1.1 SD to 0.4 SD , with a dramatic drop in weight for height from 3.8 SD to 1.2 SD . H and length increased from -1.5 SD to -0.4 SD and foot length from -2.5 SD to -1.4 SD . Body fat , measured by dual X-ray energy absorptiometry , dropped by a third , whereas muscle mass increased by a fourth . Physical capability ( Wingate test ) improved considerably . The children were reported to be much more active and capable . In group 2 , similar changes were seen , but weight for height increased , probably because muscle mass increase exceeded fat mass decrease . Changes in group 3 were similar as in group 1 , even though far less distinct . Conclusion Growth hormone treatment in Prader-Labhart-Willi syndrome led to dramatic changes : distinct increase in growth velocity , height and muscle mass , as well as an improvement in physical performance . Fat mass and weight for height decreased in the initially overweight children , and weight for height increased in underweight children CONTEXT Symptoms of fluid retention in GH-deficient patients during GH replacement  are greater in men than in women , suggesting that testosterone may augment or estradiol may attenuate the antinatriuretic actions of GH . The mechanisms underlying the sodium-retaining effects of GH are poorly understood . AIM The aim of this study was to investigate the effects of GH and testosterone , alone and in combination , on extracellular water ( ECW ) and the hormonal mechanisms involved . DESIGN Two separate , open-label , r and omized , two-period , crossover studies were performed ; the first compared the effects of GH alone with those of GH and testosterone , and the second compared the effects of testosterone alone with those of GH and testosterone . PARTICIPANTS Twelve hypopituitary men with GH deficiency and hypogonadism were studied . INTERVENTION During the weeks of intervention , GH ( 0.5 mg/d ) and testosterone enanthate ( 250 mg ) were administered by i m injection . OUTCOME MEASURES The outcome measures were ECW , IGF-I , plasma renin activity ( PRA ) , aldosterone ( Aldo ) , and atrial natriuretic peptide ( ANP ) . RESULTS GH treatment significantly increased ( P < 0.05 ) both IGF-I and ECW , and these changes were enhanced by cotreatment with testosterone ( P = 0.07 for both ) . PRA , Aldo , and ANP levels did not change . Testosterone treatment alone did not change the IGF-I concentration , whereas cotreatment with GH induced a marked increase . Testosterone alone increased ( P < 0.05 ) ECW , and the effect was augmented ( P < 0.01 ) by cotreatment with GH . Although PRA and ANP did not change , plasma Aldo decreased after single and combined treatments . CONCLUSION GH and testosterone exerted independent and additive effects on ECW . The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules . This is the first direct evidence that testosterone increases ECW 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 We studied the acute effects of a single , sc GH dose on exercise performance and metabolism during bicycling . Seven highly trained men [ age , 26 + /- 1 yr ( mean + /- SEM ) ; weight , 77 + /- 3 kg ; maximal oxygen uptake , 65 + /- 1 ml O(2).min(-1).kg(-1 ) ] performed 90 min of bicycling 4 h after receiving 7.5 IU ( 2.5 mg ) GH or placebo in a r and omized , double-blinded , cross-over design trial . A st and ardized pre-exercise meal was given 2 h before exercise . Blood was sample d at rest and during exercise and analyzed for GH , IGF-I , glucose , lactate , insulin , glycerol , and nonesterified fatty acids ( NEFA ) . In the placebo trial , all subjects completed the exercise protocol without any difficulties . In contrast , two subjects were not able to complete the exercise protocol in the GH trial , and one subject barely managed to complete the protocol . In addition , GH administration result ed in exaggerated increases in plasma lactate concentrations during exercise ( P < 0.0001 ) . The combined lipolytic effect of GH and exercise , evidence d by increased plasma glycerol and serum NEFA concentrations , was 3-fold greater than the effect of exercise alone ( P < 0.0001 ) , but this increased substrate availability did not result in increased whole body fat oxidation ( indirect calorimetry ) . Plasma glucose was , on average , 9 % higher during exercise after GH administration compared with placebo ( P < 0.0001 ) . We conclude that a single , relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity . The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance Background / Aims : Recombinant human growth hormone ( rhGH ) as opposed to cadaver pituitary GH is misused for physical improvement . Six days ’ rhGH administration , in abstinent anabolic- and rogenic steroid dependents , was compared with controls . Method : Male subjects ( n = 48 ) were r and omly divided into two groups : ( 1 ) : control group ( C ) , n = 24 , mean ± SD , age 32 ± 11 years , height 1.8 ± 0.06 m ; ( 2 ) :  rhGH-using group  ( 0.058 IU·kg–1·day–1 ) ( GH ) , n = 24 , mean ± SD , age 32 ± 9 years , height 1.8 ± 0.07 m. Physiological measurements included anthropometry , strength , power and peak oxygen uptake ( VO2 peak ) . Biochemical measurements included haemoglobin , packed cell volume , glucose , sodium , potassium , urea , creatinine , total protein , albumin , thyroid function , testosterone , prolactin , cortisol , GH and insulin-like growth factor-I ( IGF-I ) . Results : Strength , peak power output and IGF-I significantly increased and total protein , albumin and free tetra-iodothyronine significantly decreased compared to controls ( p < 0.05 ) and within the GH group ( p < 0.017 ) . Fat-free mass index and VO2 peak significantly increased , while body fat and thyroid-stimulating hormone significantly decreased within the GH group ( p < 0.017 ) . Conclusions : Short-term rhGH  increased strength and power . Of therapeutic value is the possibility that muscle bulk and strength could be increased in patients with muscle-wasting conditions The effect of recombinant GH on strength , body composition and endocrine parameters in power athletes was investigated in a controlled study . Twenty-two healthy , non-obese males ( age 23.4 + /- 0.5 years ; ideal body weight 122 + /- 3.1 % , body fat 10.1 + /- 1.0 % ; mean + /- SEM ) were included . Prob and s were assigned in a double-blind manner to either GH treatment ( 0.09U ( kg BW)-1 day-1 sc ) or placebo for a period of six weeks . To exclude concurrent treatment with and rogenic-anabolic steroids urine specimens were tested at regular intervals for these substances . Serum was assayed for GH , IGF-I , IGF-binding proteins , insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter . Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus . Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper . For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed . GH , IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group . Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated prob and s. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles . Body weight and body fat were not changed significantly during treatment . We conclude that the anabolic , lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Hormone administration to elderly individuals can increase lean body mass ( LBM ) and decrease fat , but interactive effects of growth hormone ( GH ) and sex steroids and their influence on strength and endurance are unknown . OBJECTIVE To evaluate the effects of recombinant human GH and /or sex steroids on body composition , strength , endurance , and adverse outcomes in aged persons . DESIGN , SETTING , AND PARTICIPANTS A 26-week r and omized , double-blind , placebo-controlled parallel-group trial in healthy , ambulatory , community-dwelling US women ( n = 57 ) and men ( n = 74 ) aged 65 to 88 years recruited between June 1992 and July 1998 . INTERVENTIONS Participants were r and omized to receive GH ( starting dose , 30 micro g/kg , reduced to 20 micro g/kg , subcutaneously 3 times/wk ) + sex steroids ( women : transdermal estradiol , 100 micro g/d , plus oral medroxyprogesterone acetate , 10 mg/d , during the last 10 days of each 28-day cycle [ HRT ] ; men : testosterone enanthate , biweekly intramuscular injections of 100 mg ) ( n = 35 ) ; GH + placebo sex steroid ( n = 30 ) ; sex steroid + placebo GH ( n = 35 ) ; or placebo GH + placebo sex steroid ( n = 31 ) in a 2 x 2 factorial design . MAIN OUTCOME MEASURES Lean body mass , fat mass , muscle strength , maximum oxygen uptake ( VO(2)max ) during treadmill test , and adverse effects . RESULTS In women , LBM increased by 0.4 kg with placebo , 1.2 kg with HRT ( P = .09 ) , 1.0 kg with GH ( P = .001 ) , and 2.1 kg with GH + HRT ( P<.001 ) . Fat mass decreased significantly in the GH and GH + HRT groups . In men , LBM increased by 0.1 kg with placebo , 1.4 kg with testosterone ( P = .06 ) , 3.1 kg with GH ( P<.001 ) , and 4.3 kg with GH + testosterone ( P<.001 ) . Fat mass decreased significantly with GH and GH + testosterone . Women 's strength decreased in the placebo group and increased nonsignificantly with HRT ( P = .09 ) , GH ( P = .29 ) , and GH + HRT ( P = .14 ) . Men 's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone ( P = .05 ) . Women 's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH ( P = .07 ) and GH + HRT ( P = .06 ) . Men 's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone ( P = .49 ) but increased with GH ( P = .11 ) and with GH + testosterone ( P<.001 ) . Changes in strength ( r = 0.355 ; P<.001 ) and in VO(2)max ( r = 0.320 ; P = .002 ) were directly related to changes in LBM . Edema was significantly more common in women taking GH ( 39 % vs 0 % ) and GH + HRT ( 38 % vs 0 % ) . Carpal tunnel symptoms were more common in men taking GH + testosterone ( 32 % vs 0 % ) and arthralgias were more common in men taking GH ( 41 % vs 0 % ) . Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH ( P = .006 ) . CONCLUSIONS In this study , GH with or without sex steroids in healthy , aged women and men increased LBM and decreased fat mass .  Sex steroid + GH increased muscle strength marginally and VO ( 2)max in men , but women had no significant change in strength or cardiovascular endurance . Because adverse effects were frequent ( importantly , diabetes and glucose intolerance ) , GH interventions in the elderly should be confined to controlled studies Initiation of  GH treatment in adults is frequently complicated by the development of symptomatic fluid retention . To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults , we conducted a double blind study in which seven GH-deficient patients ( aged 24 - 74 yr ) each received in r and om order daily sc injections of placebo , a physiological dose of GH ( 0.04 U/kg , low dose ) , and a supraphysiological dose of GH ( 0.08 U/kg , high dose ) for 7 days , separated by 21-day washout periods . On the seventh day , measurements were made of serum insulin-like growth factor I , body weight , exchangeable sodium , plasma volume , angiotensinogen , PRA , aldosterone , atrial natriuretic peptide ( ANP ) , and mean 24-h ambulatory heart rate and blood pressure . GH significantly increased mean insulin-like growth factor I levels from 105 + /- 11 to 304 + /- 45 micrograms/L during low dose treatment ( P = 0.006 ) and 400 + /- 76 micrograms/L during high dose treatment ( P = 0.004 ) . High dose GH caused a 1.2 + /- 0.3 kg increase in body weight ( P = 0.01 ) and a 193 + /- 65 mmol increase in exchangeable sodium ( P = 0.008 ) . Low dose GH had a lesser effect , with no significant increase in body weight , but an increase in exchangeable sodium of 113 + /- 37 mmol ( P = 0.02 ) . Plasma volume was not significantly affected by GH treatment . Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo ( low dose , P = 0.017 ; high dose , P = 0.028 ) as were mean supine PRA levels ( low dose , P = 0.0002 ; high dose , P = 0.0025 ) . Supine angiotensin II , aldosterone , and ANP levels were not significantly affected by GH treatment . There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture . The mean 24-h heart rate was significantly higher during low dose ( 82 + /- 2 beats/min ; P = 0.0001 ) and high dose ( 88 + /- 3 beats/min ; P = 0.0001 ) GH treatment than during placebo ( 67 + /- 3 beats/min ) . However , no significant change in mean 24-h systolic or diastolic blood pressure was observed . In summary , acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium , but no associated increase in blood pressure . We conclude that 1 ) sodium retention is a physiological effect of GH , but does not cause an acute rise in blood pressure ; and 2 ) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release , but more likely to a direct renal tubular effect Measurements of serum insulin-like growth factor I ( IGF-I ) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess . The validity of these markers for assessment of exogenous GH exposure in healthy adults is , however , unknown . We therefore conducted a double blind , placebo-controlled GH treatment trial in 99 healthy subjects [ 49 women and 50 men ; mean + /- SE age , 25.6+/-0.6 (women)/25.7+/-0.6 yr ( men ) ] .  Blood  was collected weekly during a 4-week treatment period ( days 1 - 28 ) , and the subjects were subsequently followed for additional 8 weeks ( days 29 - 84 ) . The treatment arms included : I ) 0.1 IU/kg x day GH ( n = 30 ; GH 0.1 ) , II ) 0.2 IU/kg x day GH ( n = 29 ; GH 0.2 ) , and III ) placebo ( n = 40 ) . At baseline no gender-specific differences existed , except that the acid-labile subunit ( ALS ) levels were higher in females . Serum insulin-like growth factor I ( IGF-I ) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses . The absolute IGF-I response was significantly lower in females , and there was a clear dose-response relationship . ALS levels in males increased through day 30 ( P < 0.001 ) . In females ALS levels were only modestly increased on day 28 compared with those in the placebo group ( P < 0.02 ) . IGF-binding protein-3 ( IGFBP-3 ) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 ( P < 0.03 ) , whereas no solid IGFBP-3 increase was detected in females . IGFBP-2 levels decreased insignificantly during GH exposure in both genders . A gender-specific upper normal range for each analyte was arbitrarily defined as 4 SD above the mean level at baseline . On the basis of IGF-I levels alone , GH exposure in the GH 0.2 group was detected in 86 % of the males and in 50 % of the females on day 21 . On day 42 GH exposure was only weakly detectable in males and was not detectable in females . We conclude that 1 ) males are significantly more responsive than females to exogenous GH ; 2 ) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS ; 3 ) IGFBP-2 changes very little during GH treatment ; and 4 ) among IGF-related substances , IGF-I is the most specific marker of supraphysiological GH exposure
target: RESULTS Body cell mass was correlated with all measures of performance at baseline .
  Growth hormone significantly reduced fat mass , increased lean body mass through an increase in extracellular water , and increased body cell mass in men when coadministered with testosterone .
  Growth hormone supplementation influenced body composition and increased sprint capacity when administered alone and in combination with testosterone .
background: BACKGROUND Growth hormone is widely abused by athletes , frequently with and rogenic steroids .
  Its effects on performance are unclear .
  OBJECTIVE To determine the effect of growth hormone alone or with testosterone on body composition and measures of performance .