title: Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) Effects of GH on cognitive function in elderly patients with adult-onset GH deficiency: a placebo-controlled 12-month study. Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability Body composition. Prediction of normal body potassium, body water and body fat in adults on the basis of body height, body weight and age. The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency. Serum insulin‐like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin The effects of five‐year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. A low starting dose of genotropin in growth hormone-deficient adults. Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement.
abstract: Abdominal obesity is associated with blunted GH secretion and a cluster of cardiovascular risk factors that characterize the metabolic syndrome . GH treatment in abdominally obese men reduces visceral adipose tissue and has beneficial effects on the metabolic profile . There are no long-term data on the effects of GH treatment on postmenopausal women with abdominal obesity . Forty postmenopausal women with abdominal obesity participated in a r and omized , double-blind , placebo-controlled , 12-month trial with GH ( 0.67 mg/d ) . The primary aim was to study the effect of GH treatment on insulin sensitivity . Measurements of glucose disposal rate ( GDR ) using a euglycemic , hyperinsulinemic glucose clamp ;  abdominal fat , hepatic fat content , and thigh muscle area using computed tomography ; and total body fat and fat-free mass derived from (40)K measurements were performed at baseline and at 6 and 12 months . GH treatment reduced visceral fat mass , increased thigh muscle area , and reduced total and low-density lipoprotein cholesterol compared with placebo .  Insulin sensitivity was increased at 12 months compared with baseline values in the GH-treated group . In the GH-treated group only , a low baseline GDR was correlated with a more marked improvement in insulin sensitivity ( r = -0.68 ; P < 0.001 ) . A positive correlation was found between changes in GDR and liver attenuation as a measure of hepatic fat content between baseline and 12 months ( r = 0.7 ; P < 0.001 ) in the GH-treated group . In postmenopausal women with abdominal obesity , 1 yr of GH treatment improved insulin sensitivity and reduced abdominal visceral fat and total and low-density lipoprotein cholesterol concentrations . The improvement in insulin sensitivity was associated with reduced hepatic fat content Background — Statins are important in vascular disease prevention in the elderly . However , the best method of selecting older patients for treatment is uncertain . We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Method and Results — The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER .  Baseline LDLc showed no relation to risk of the primary end point in the placebo group ( P=0.27 ) , nor did on-treatment LDLc in the pravastatin group ( P=0.12 ) . HDLc was inversely associated with risk in subjects on placebo ( P=0.0019 ) but not in those on pravastatin ( P=0.24 ) . Risk reduction on pravastatin treatment was unrelated to baseline LDLc ( P=0.38 ) but exhibited a significant interaction with HDLc ( P=0.012 ) . Subjects in the lowest 2 quintiles of HDLc ( < 1.15 mmol/L ) had a risk reduction of 33 % ( hazard ratio , 0.67 ; 95 % confidence limits , 0.55 , 0.81 ; P<0.0001 ) , whereas those with higher HDLc showed no benefit ( RR , 1.06 ; 95 % confidence limits , 0.88 , 1.27 ; P=0.53 ) . During follow-up , there was no relation between achieved level of LDLc or HDLc and risk . However , the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy . Conclusions — In people > 70 years old , HDLc appears to be a key predictor of risk and of treatment benefit . Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc < 1.15 mmol/L or an LDLc/HDLc ratio > 3.3 OBJECTIVE Young adults with childhood-onset GH deficiency ( GHD ) have reduced memory and attention , which can be improved by treatment with GH . Little information is available on cognitive function in elderly GHD patients . DESIGN Single center , double-blind , r and omized , placebo-controlled study of 52-week duration . METHODS Elderly GH therapy naïve GHD patients ( n=34 ; age range 60 - 77 years ) were enrolled and r and omized to receive placebo or GH therapy which was titrated to achieve a target IGF-I level of + 1 to + 2 s.d . of the normal mean for age . Cognitive function was assessed at baseline and after 24 and 52 weeks , using a computerized psychometric test package ( Neurobehavioral Examination System-2 ) . RESULTS The mean GH dose was 0.16+/-0.06 mg/day ; mean IGF-I increased from 135+/-59 ng/ml at baseline to 213+/-77 ng/ml during active treatment . The GH-treated group had better mean serial digit learning scores compared with placebo group ( P<0.05 ) . Assessment of effect sizes showed that improvements in memory occurred with GH after 24 weeks . The overall adverse event rates were similar in the GH and the placebo group . CONCLUSION This study indicates that GH replacement may be accompanied by improvement in certain measures of cognitive function in elderly patients with GHD 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 In 134 males and 242 females , aged 20 - 70 years , most of them r and omly selected from population studies , the body composition was estimated from the measurements of body height ( BH ) , body weight ( BW ) , total body potassium ( TBK ) and total body water ( TBW ) . TBK was measured with isotope dilution technique using 42 K or determined as 40 K in a whole body counter .  TBW was determined with an isotope dilution technique using tritiated water , assayed in urine or plasma . From these data , body cell mass ( BCM ) , intra- and extra-cellular water ( ICW and ECW , resp . ) and body fat ( BF ) were calculated for each individual . Significant correlations were found between age versus TBK , ECW , BF and ECW/ICW ; between BW versus TBK , TBW , ECW , BF and ECW/ICW ; ( females only ) and between BH versus TBK , TBW , ECW ( females only ) and ECW/ICW . For the prediction of TBK , TBW and BF , multiple regression equations based on BW , BH and age are given . These equations are also presented diagrammatically . The problems with the methods used are considered as well as the applicability of the formulas for the calculation of BCM etc . The predictive value of the results when both TBW and TBK are used for the calculation of body composition data is discussed and compared with similar results , based on TBW or TBK only . It is concluded , that the most reliable method for calculation of BF is to estimate both TBW and TBK objectives To assess effects of GH replacement therapy on cardiac structure and function , exercise capacity as well as serum lipids in elderly patients with GH deficiency ( GHD ) CONTEXT The effects of GH replacement in elderly GH-deficient ( GHD ) adults are not well known . OBJECTIVE / DESIGN / PATIENTS In this prospect i ve , single-center , open-label study , baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients ( mean age , 37 yr ; range , 27 - 46 yr ) . All patients had adult onset disease , and both groups were comparable in terms of the number of pituitary hormonal deficiencies , gender , body mass index , and waist/hip ratio . Duration of hypopituitarism was , however , longer in the elderly patients . RESULTS The mean maintenance dose of GH was 0.31 ( sem , 0.03 ) mg/d in the elderly GHD patients and 0.44 ( 0.04 ) mg/d in the younger patients . The less marked response in IGF-I sd score , total body fat , and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses . Despite the lower dose in the elderly GHD group , these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level , and these differences remained also after correction for duration of hypopituitarism . There was no difference at baseline or in responsiveness in lean mass , bone mineral density , and glucose homeostasis . CONCLUSIONS This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism .  GH replacement should therefore be considered in elderly GHD adults OBJECTIVE There Is a cllnlcal need for population based reference values for serum Insulin‐like growth factor I ( IGF‐I ) . We have therefore determined serum IGF‐i  concentrations In a r and om population sample from Sweden and have related the levels to age , sex , llfe style factors , blood pressure , body composition , blood llplds , plasma fibrlnogen , Parathyroid hormone ( PTH ) and osteocalcin Objective Little is known of the long‐term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency ( GHD ) . In this study , the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD Although growth hormone ( GH ) replacement therapy is increasingly utilized in the management of adult hypopituitary patients , optimum dosing schedules are poorly defined . The use of weight-based or surface area-based dosing may result in overtreatment , and individual variation in susceptibility on the basis of gender and other factors is now being recognized . To optimize GH replacement and to explore further gender differences in susceptibility , we used a dose titration regimen , starting at the initiation of GH replacement therapy , in 50 consecutive adult-onset hypopituitary patients , and compared the results with those in 21 patients previously treated using a weight-based regimen . Titrated patients commenced GH 0.8 IU/day subcutaneously ( 0.4 IU/day if hypertensive or glucose tolerance impaired ) . Serum insulin-like growth factor I ( IGF-I ) was measured at 0 , 2 , 4 , 6 , 8 , 10 , and 12 weeks in all patients . Serum IGF binding protein 3 and acid labile subunit were measured at the same time points in 17 patients ( 8 male , 9 female ) . Patients were review ed every 4 weeks and the dose of GH increased , if necessary , to achieve a serum IGF-I level between the median and the upper end of the age-related reference range . There was no significant difference between mean serum IGF-I at 2 and 4 weeks , or between 6 and 8 weeks , indicating that the full effects of a change in dose are evident within 2 weeks of that change . Maintenance doses were significantly higher in females than males [ 1.2 ( 0.8 - 2.0 ) vs. 0.8 ( 0.4 - 1.6 ) IU/day ; median ( range ) ; P < 0.0001 ] , and the median time to achieve maintenance dose was significantly shorter in males [ 4 ( 2 - 12 ) vs. 9 ( 2 - 26 ) weeks ; P < 0.0001 ] . Median maintenance dose was lower overall than in a group of 21 patients initially commenced on GH using a weight-based dosing schedule , with subsequent adjustment of dose during clinical follow-up [ 1.5 ( 0.4 - 3.2 ) IU/day ; P = 0.02 ] . Reduction in waist measurement and waist to hip ratio at 6 and 12 months was similar in females ( P < 0.001 ) and males ( P < 0.01 ) . Well-being improved significantly after 3 months of GH therapy ( 14.2 + /- 5.9 vs. 7.4 + /- 4.5 SD ; P < 0.0001 ) , and there were no gender differences . Adult Growth Hormone Deficiency Assessment ( AGHDA ) scores at 6 months were similar to maintenance scores in patients commenced on weight-based regimens . Measurements of ALS and IGFBP-3 added no useful extra information to IGF-I in managing the dose titration . The practical scheme outlined for dose titration of GH replacement result ed in rapid achievement of lower maintenance doses than those achieved using conventional weight-based regimens without loss of efficacy . It was particularly important in female patients who demonstrated decreased overall sensitivity to GH  and required higher doses to achieve the same effects as males . This constitutes the first report of a uniform titration regimen based on a defined target range of serum IGF-I in a large patient cohort We investigated the effect of 12 weeks of recombinant human GH therapy given in three different doses on serum insulin-like growth factor I ( IGF-I ) and IGF-binding protein-3 ( IGFBP-3 ) in patients with GH deficiency ( GHD ) . We used low doses of recombinant human GH ( Genotropin ) , as we and others recently found a strong decrease in physiological GH production with age in healthy controls , especially in those older than 30 yr . Sixty patients with GHD ( aged 20 - 70 yr ) were r and omized to one of the three dose groups . Group 1 used a dose of 0.6 IU/day for 12 weeks . Group 2 started at a dose of 0.6 IU for 4 weeks followed by 1.2 IU/day for 8 weeks . Group 3 used 0.6 IU for 4 weeks , followed by 1.2 IU/day for 4 weeks and 1.8 IU/day thereafter . IGF-I concentrations ( nanomoles per L ) were determined by RIA after extraction and purification on ODS-silica columns . The measurement of IGFBP-3 ( milligrams per L ) was performed by RIA . The three groups were equal with regard to age , sex and body mass index . At the start of the study , we found lower levels of both serum IGF-I and IGFBP-3 in childhood-onset GHD than in adult-onset GHD . Moreover , there was a gender difference ; female GHD patients had lower serum IGF-I levels than male patients .  Serum IGF-I levels were low in both childhood-onset and adult-onset GHD . Serum IGFBP-3 levels , however , were low in patients with childhood-onset GHD , but normal in patients with adult-onset GHD . After 12 weeks of treatment , IGF-I levels were low normal in the low dose group and normal in groups 2 and 3 of both adult-onset and childhood-onset GHD . In adult-onset GHD , serum IGFBP-3 increased to high normal levels in all groups , whereas it increased to low normal levels in childhood-onset GHD . This study demonstrates differences in the biochemical characteristics of childhood-onset and adult-onset GHD . In patients with adult-onset GHD , serum IGFBP-3 levels are not significantly decreased and , therefore , can not be used as a screening method for GHD or as a dose-finding parameter . GH therapy at doses of 0.6 and 1.2 IU/day in male and female patients , respectively , is , in general , able to increase serum IGF-I into the normal range after 12 weeks of treatment , without reaching supranormal levels of serum IGF-I. This dose could , therefore , be a starting dose in GH-deficient adults CONTEXT Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency ( GHD ) . OBJECTIVE , DESIGN , AND PATIENTS : In this prospect i ve open-labeled study , the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults ( mean age of 65.2 years ; range 61 - 74 years ) .  Muscle strength was compared with reference values obtained from the background population . RESULTS The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day . The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end . GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength . Isometric knee extensor strength was reduced after 10 years . However , after correction for age and gender , using observed/predicted value ratios , there was sustained and even progressive increase in most variables reflecting muscle strength . Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years . CONCLUSIONS Ten years of GH replacement therapy in elderly GHD adults result ed in a transient increase in isometric knee flexor strength , and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function
target: RhGh did not consistently affect blood pressure or bone mineral density .
  RhGH consistently improved quality of life ( QoL ) parameters reflected in AGHDA-scores .
  Conclusion RhGH replacement in elderly subjects with GHD  decreases LDL cholesterol levels and improves QoL , but the effects on other parameters are not unequivocal .
  There were no data on the efficacy and safety  of rhGH treatment in octogenarians with GHD
background: Context Recombinant human GH ( rhGH ) is prescribed for the treatment of adults with GH deficiency ( GHD ) .
  However , conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients .
  Objective To assess the efficacy of rhGH treatment in elderly GHD subjects .