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: CONTEXT Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation . Trial 's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm . The changes in muscle performance and physical function were evaluated in relation to participant 's perception of change . METHODS Men aged 65 years and older , with mobility limitation , total testosterone 100 - 350 ng/dL , or free testosterone less than 50 pg/mL , were r and omized to placebo or 10 g testosterone gel daily for 6 months . Primary outcome was leg-press strength . Secondary outcomes included chest-press strength , stair-climb , 40-m walk , muscle mass , physical activity , self-reported function , and fatigue . Proportions of participants exceeding minimally important difference in study arms were compared . RESULTS Of 209 r and omized participants , 165 had follow-up efficacy measures . Mean ( SD ) age was 74 ( 5.4 ) years and short physical performance battery score 7.7 ( 1.4 ) .  Testosterone arm exhibited greater improvements in leg-press strength , chest-press strength and power , and loaded stair-climb than placebo . Compared with placebo , significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths ( 43 % vs 18 % , p = .01 ) and stair-climbing power ( 28 % vs 10 % , p = .03 ) more than minimally important difference . Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass . Physical activity , walking speed , self-reported function , and fatigue did not change . CONCLUSIONS Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power . Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) .  Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have  serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy CONTEXT Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and and rogenic alopecia , but the role of 5α-dihydrotestosterone ( DHT ) in mediating testosterone 's effects on muscle , sexual function , erythropoiesis , and other and rogen-dependent processes remains poorly understood . OBJECTIVE To determine whether testosterone 's effects on muscle mass , strength , sexual function , hematocrit level , prostate volume , sebum production , and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride ( an inhibitor of 5α-reductase type 1 and 2 ) . DESIGN , SETTING , AND PATIENTS The 5α-Reductase Trial was a r and omized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010 . INTERVENTIONS Eight treatment groups received 50 , 125 , 300 , or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo ( 4 groups ) or 2.5 mg/d of dutasteride ( 4 groups ) . MAIN OUTCOME MEASURES The primary outcome was change in fat-free mass ; secondary outcomes : changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels . RESULTS A total of 139 men were r and omized ; 102 completed the 20-week intervention . Men assigned to dutasteride were similar at baseline to those assigned to placebo . The mean fat-free mass gained by the dutasteride groups was 0.6 kg ( 95 % CI , -0.1 to 1.2 kg ) when receiving 50 mg/wk of testosterone enanthate , 2.6 kg ( 95 % CI , 0.9 to 4.3 kg ) for 125 mg/wk , 5.8 kg ( 95 % CI , 4.8 to 6.9 kg ) for 300 mg/wk , and 7.1 kg ( 95 % CI , 6.0 to 8.2 kg ) for 600 mg/wk . The mean fat-free mass gained by the placebo groups was 0.8 kg ( 95 % CI , -0.1 to 1.7 kg ) when receiving 50 mg/wk of testosterone enanthate , 3.5 kg ( 95 % CI , 2.1 to 4.8 kg ) for 125 mg/wk , 5.7 kg ( 95 % CI , 4.8 to 6.5 kg ) for 300 mg/wk , and 8.1 kg ( 95 % CI , 6.7 to 9.5 kg ) for 600 mg/wk . The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant ( P = .18 ) . Changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels did not differ between groups . CONCLUSION Changes in fat-free mass in response to grade d testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo , indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00493987 Aging in men is associated with loss of bone mass , impaired physical function and altered body composition . The objective of this proof‐of‐concept r and omized , double‐blind , placebo‐controlled , parallel‐group , single‐center trial was to determine the relative effects of testosterone ( T ) and estradiol ( E2 ) on bone mineral density , body composition , and physical performance in older men . The primary outcome was lumbar spine bone mineral density ( BMD ) , and secondary outcomes were body composition , muscle strength , gait speed , and sex hormone concentrations . Forty three men ( age range , 65–82 years ; mean age 71 years ) with low total T levels < 350 ng/dL were r and omized to one of three groups : 5 g transdermal testosterone gel ( TT ) ( N = 16 ) , anastrozole ( AI ) 1 mg ( N = 14 ) or placebo daily ( N = 13 ) for 12 months . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Both TT and AI increased serum TT levels ( > 500 ng/dL , p < 0.05 ) compared to baseline ; T values remained stable throughout the duration of the trial . At 12 months , TT improved the primary outcome of lumbar spine BMD ( p < 0.01).Both interventions improved knee strength at 12 months compared to baseline ( p < 0.05 ) while lean body mass significantly increased only in the AI group at 6 and 12 months ( 1.49 ± 0.38 kg , p < 0.01 ; 1.24 ± 0.39 kg , p < 0.05 , respectively ) compared to baseline . Interestingly , TT improved fast gait speed at 3 and 12 months ( p < 0.01 , p < 0.05 , respectively ) . In summary , this proof‐of‐concept study confirms that aromatization of T is required for maintaining BMD in older men with low‐T levels . The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed , an observation that needs to be verified in future studies Context : Findings of studies of testosterone ’s effects on muscle strength and physical function  in older men have been inconsistent ; its effects on muscle power and fatigability have not been studied . Objective : To determine the effects of testosterone administration for 3 years in older men on  muscle strength , power , fatigability , and physical function . Design , Setting , and Participants : This was a double-blind , placebo-controlled , r and omized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels < 50 pg/mL. Interventions : R and om assignment to 7.5 g of 1 % testosterone or placebo gel daily for 3 years . Outcome Measures : Loaded and unloaded stair-climbing power , muscle strength , power , and fatigability in leg press and chest press exercises , and lean mass at baseline , 6 , 18 , and 36 months . Results : The groups were similar at baseline . Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power  than placebo ( mean estimated between-group difference , 10.7 W [ 95 % confidence interval ( CI ) , −4.0 to 25.5 ] , P = 0.026 ; and 22.4 W [ 95 % CI , 4.6 to 40.3 ] , P = 0.027 ) , respectively . Changes in chest-press strength ( estimated mean difference , 16.3 N ; 95 % CI , 5.5 to 27.1 ; P < 0.001 ) and power ( mean difference 22.5 W ; 95 % CI , 7.5 to 37.5 ; P < 0.001 ) , and leg-press power were significantly greater in men r and omized to testosterone than in those r and omized to  placebo . Lean body mass significantly increased more in the testosterone group . Conclusion : Compared with placebo , testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power , muscle mass , and power . Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied OBJECTIVES To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass ( LBM ) in aging men with low-normal testosterone levels in a r and omized , double-blind , placebo-controlled 24-week study . DESIGN R and omized , double-blind , placebo-controlled . SETTING Odense , Denmark . PARTICIPANTS Men aged 60 to 78 , with bioavailable testosterone levels of less than 7.3 nmol/L and a waist circumference greater than 94 cm were r and omized to testosterone  ( 50 - 100 mg/d , n = 22 ) placebo ( n = 23 ) or strength training  ( n = 23 ) for 24 weeks . The strength training group was r and omized to addition of testosterone or placebo after 12 weeks . Subjects performed supervised strength training ( 2 - 3 sets with 6- to 10-repetition maximum loads , 3 times per week ) . MEASUREMENTS Testosterone levels , maximal voluntary contraction and rate of force development , and LBM were obtained at 0 and at Weeks 12 and 24 of the intervention . RESULTS No changes in any variables were recorded with placebo . In the strength training group , maximal voluntary contraction increased 8 % after 12 weeks ( P = .005 ) . During the following 12 weeks of strength training rate of force development increased by 10 % ( P = .04 ) and maximal voluntary contraction further increased ( P < .001 ) . Mechanical muscle function was unchanged in 
    Output:
    
agent
Intramuscular TRT is more effective than transdermal formulations at increasing LBM and improving muscle strength  in middle-aged and older men , particularly in the lower extremities
***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: CONTEXT Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation . Trial 's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm . The changes in muscle performance and physical function were evaluated in relation to participant 's perception of change . METHODS Men aged 65 years and older , with mobility limitation , total testosterone 100 - 350 ng/dL , or free testosterone less than 50 pg/mL , were r and omized to placebo or 10 g testosterone gel daily for 6 months . Primary outcome was leg-press strength . Secondary outcomes included chest-press strength , stair-climb , 40-m walk , muscle mass , physical activity , self-reported function , and fatigue . Proportions of participants exceeding minimally important difference in study arms were compared . RESULTS Of 209 r and omized participants , 165 had follow-up efficacy measures . Mean ( SD ) age was 74 ( 5.4 ) years and short physical performance battery score 7.7 ( 1.4 ) .  Testosterone arm exhibited greater improvements in leg-press strength , chest-press strength and power , and loaded stair-climb than placebo . Compared with placebo , significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths ( 43 % vs 18 % , p = .01 ) and stair-climbing power ( 28 % vs 10 % , p = .03 ) more than minimally important difference . Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass . Physical activity , walking speed , self-reported function , and fatigue did not change . CONCLUSIONS Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power . Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) .  Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have  serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy CONTEXT Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and and rogenic alopecia , but the role of 5α-dihydrotestosterone ( DHT ) in mediating testosterone 's effects on muscle , sexual function , erythropoiesis , and other and rogen-dependent processes remains poorly understood . OBJECTIVE To determine whether testosterone 's effects on muscle mass , strength , sexual function , hematocrit level , prostate volume , sebum production , and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride ( an inhibitor of 5α-reductase type 1 and 2 ) . DESIGN , SETTING , AND PATIENTS The 5α-Reductase Trial was a r and omized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010 . INTERVENTIONS Eight treatment groups received 50 , 125 , 300 , or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo ( 4 groups ) or 2.5 mg/d of dutasteride ( 4 groups ) . MAIN OUTCOME MEASURES The primary outcome was change in fat-free mass ; secondary outcomes : changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels . RESULTS A total of 139 men were r and omized ; 102 completed the 20-week intervention . Men assigned to dutasteride were similar at baseline to those assigned to placebo . The mean fat-free mass gained by the dutasteride groups was 0.6 kg ( 95 % CI , -0.1 to 1.2 kg ) when receiving 50 mg/wk of testosterone enanthate , 2.6 kg ( 95 % CI , 0.9 to 4.3 kg ) for 125 mg/wk , 5.8 kg ( 95 % CI , 4.8 to 6.9 kg ) for 300 mg/wk , and 7.1 kg ( 95 % CI , 6.0 to 8.2 kg ) for 600 mg/wk . The mean fat-free mass gained by the placebo groups was 0.8 kg ( 95 % CI , -0.1 to 1.7 kg ) when receiving 50 mg/wk of testosterone enanthate , 3.5 kg ( 95 % CI , 2.1 to 4.8 kg ) for 125 mg/wk , 5.7 kg ( 95 % CI , 4.8 to 6.5 kg ) for 300 mg/wk , and 8.1 kg ( 95 % CI , 6.7 to 9.5 kg ) for 600 mg/wk . The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant ( P = .18 ) . Changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels did not differ between groups . CONCLUSION Changes in fat-free mass in response to grade d testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo , indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00493987 Aging in men is associated with loss of bone mass , impaired physical function and altered body composition . The objective of this proof‐of‐concept r and omized , double‐blind , placebo‐controlled , parallel‐group , single‐center trial was to determine the relative effects of testosterone ( T ) and estradiol ( E2 ) on bone mineral density , body composition , and physical performance in older men . The primary outcome was lumbar spine bone mineral density ( BMD ) , and secondary outcomes were body composition , muscle strength , gait speed , and sex hormone concentrations . Forty three men ( age range , 65–82 years ; mean age 71 years ) with low total T levels < 350 ng/dL were r and omized to one of three groups : 5 g transdermal testosterone gel ( TT ) ( N = 16 ) , anastrozole ( AI ) 1 mg ( N = 14 ) or placebo daily ( N = 13 ) for 12 months . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Both TT and AI increased serum TT levels ( > 500 ng/dL , p < 0.05 ) compared to baseline ; T values remained stable throughout the duration of the trial . At 12 months , TT improved the primary outcome of lumbar spine BMD ( p < 0.01).Both interventions improved knee strength at 12 months compared to baseline ( p < 0.05 ) while lean body mass significantly increased only in the AI group at 6 and 12 months ( 1.49 ± 0.38 kg , p < 0.01 ; 1.24 ± 0.39 kg , p < 0.05 , respectively ) compared to baseline . Interestingly , TT improved fast gait speed at 3 and 12 months ( p < 0.01 , p < 0.05 , respectively ) . In summary , this proof‐of‐concept study confirms that aromatization of T is required for maintaining BMD in older men with low‐T levels . The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed , an observation that needs to be verified in future studies Context : Findings of studies of testosterone ’s effects on muscle strength and physical function  in older men have been inconsistent ; its effects on muscle power and fatigability have not been studied . Objective : To determine the effects of testosterone administration for 3 years in older men on  muscle strength , power , fatigability , and physical function . Design , Setting , and Participants : This was a double-blind , placebo-controlled , r and omized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels < 50 pg/mL. Interventions : R and om assignment to 7.5 g of 1 % testosterone or placebo gel daily for 3 years . Outcome Measures : Loaded and unloaded stair-climbing power , muscle strength , power , and fatigability in leg press and chest press exercises , and lean mass at baseline , 6 , 18 , and 36 months . Results : The groups were similar at baseline . Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power  than placebo ( mean estimated between-group difference , 10.7 W [ 95 % confidence interval ( CI ) , −4.0 to 25.5 ] , P = 0.026 ; and 22.4 W [ 95 % CI , 4.6 to 40.3 ] , P = 0.027 ) , respectively . Changes in chest-press strength ( estimated mean difference , 16.3 N ; 95 % CI , 5.5 to 27.1 ; P < 0.001 ) and power ( mean difference 22.5 W ; 95 % CI , 7.5 to 37.5 ; P < 0.001 ) , and leg-press power were significantly greater in men r and omized to testosterone than in those r and omized to  placebo . Lean body mass significantly increased more in the testosterone group . Conclusion : Compared with placebo , testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power , muscle mass , and power . Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied OBJECTIVES To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass ( LBM ) in aging men with low-normal testosterone levels in a r and omized , double-blind , placebo-controlled 24-week study . DESIGN R and omized , double-blind , placebo-controlled . SETTING Odense , Denmark . PARTICIPANTS Men aged 60 to 78 , with bioavailable testosterone levels of less than 7.3 nmol/L and a waist circumference greater than 94 cm were r and omized to testosterone  ( 50 - 100 mg/d , n = 22 ) placebo ( n = 23 ) or strength training  ( n = 23 ) for 24 weeks . The strength training group was r and omized to addition of testosterone or placebo after 12 weeks . Subjects performed supervised strength training ( 2 - 3 sets with 6- to 10-repetition maximum loads , 3 times per week ) . MEASUREMENTS Testosterone levels , maximal voluntary contraction and rate of force development , and LBM were obtained at 0 and at Weeks 12 and 24 of the intervention . RESULTS No changes in any variables were recorded with placebo . In the strength training group , maximal voluntary contraction increased 8 % after 12 weeks ( P = .005 ) . During the following 12 weeks of strength training rate of force development increased by 10 % ( P = .04 ) and maximal voluntary contraction further increased ( P < .001 ) . Mechanical muscle function was unchanged in 
    Output:
    