human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    