Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Effect of high versus low-velocity resistance training on muscular fitness and functional performance in older men Creatine Monohydrate and Conjugated Linoleic Acid Improve Strength and Body Composition Following Resistance Exercise in Older Adults Comparative effects of single-mode vs. duration-matched concurrent exercise training on body composition, low-grade inflammation, and glucose regulation in sedentary, overweight, middle-aged men. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. The influence of Task-Related Training combined with Transcutaneous Electrical Nerve Stimulation on paretic upper limb muscle activation in patients with chronic stroke. Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. Exercise attenuates the weight-loss-induced reduction in muscle mass in frail obese older adults. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Effect of a randomised 12-week resistance training programme on muscular strength, cross-sectional area and muscle quality in women having undergone Roux-en-Y gastric bypass Strength training increases insulin action in healthy 50- to 65-yr-old men. Limb muscle dysfunction in COPD: effects of muscle wasting and exercise training. Effects of Strength Training on Physical Function: Influence of Power, Strength, and Body Composition Effects of resistance or aerobic exercise training on total and regional body composition in sedentary overweight middle-aged adults. Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial.
Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p<0.001 ) following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels  following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men  on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT  reduces dementia risk BACKGROUND Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass ( FFM ) and skeletal muscle and decreases in fat mass ( FM ) but have not reported the impact of baseline body composition . OBJECTIVE The objective of the study was to determine the effect , in nonobese aging men with symptoms of and rogen deficiency and low-normal serum testosterone levels , of testosterone therapy on total and regional body composition and hormonal and metabolic indices . METHODS Sixty healthy but symptomatic , nonobese men aged 55 yr or older with total testosterone ( TT ) levels less than 15 nm were r and omized to transdermal testosterone patches or placebo for 52 wk . Body composition , by dual-energy x-ray absorptiometry ( FM , FFM , skeletal muscle ) and magnetic resonance imaging ( abdominal sc and visceral adipose tissue , thigh skeletal muscle , and intermuscular fat ) and hormonal and metabolic parameters were measured at wk 0 and 52 . RESULTS Serum TT increased by 30 % ( P = 0.01 ) , and LH decreased by 50 % ( P < 0.001 ) . Relative to placebo , total body FFM ( P = 0.03 ) and skeletal muscle ( P = 0.008 ) were increased and thigh skeletal muscle loss was prevented ( P = 0.045 ) with testosterone therapy and visceral fat accumulation decreased ( P = 0.001 ) without change in total body or abdominal sc FM ; change in visceral fat was correlated with change in TT levels ( r2 = 0.36 ; P = 0.014 ) . There was a trend to increasing total and low-density lipoprotein cholesterol with placebo . CONCLUSION Testosterone therapy , relative to placebo , selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass . Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 This study investigated the effect of a 10-week power training ( PT ) program versus traditional resistance training ( TRT ) on functional performance , and muscular power and strength in older men . Twenty inactive volunteers ( 60–76 years old ) were r and omly assigned to a PT group ( three 8–10 repetition sets performed as fast a possible at 60 % of 1-RM ) or a TRT group ( three 8–10 repetition sets with 2–3 s contractions at 60 % of 1-RM ) . Both groups exercised 2 days/week with the same work output . Outcomes were measured with the Rikli and Jones functional fitness test and a bench and leg press test of maximal power and strength ( 1-RM ) . Significant differences between and within groups were analyzed using a two-way analysis of variance ( ANOVA ) . At 10 weeks there was a significantly ( P < 0.05 ) greater improvement in measures of functional performance in the PT group . Arm curling improved by 50 versus 3 % and a 30 s chair-st and improved by 43 versus 6 % in the PT and TRT groups , respectively . There was also a significantly greater improvement in muscular power ( P < 0.05 ) in the PT group . The bench press improved by 37 versus 13 % , and the leg press by 31 and 8 % in the PT and TRT groups , respectively . There was no significant difference between groups in improved muscular strength . It appears that in older men there may be a significantly greater improvement in functional performance and muscular power with PT versus low velocity resistance training Aging is associated with lower muscle mass and an increase in body fat . We examined whether creatine monohydrate ( CrM ) and conjugated linoleic acid ( CLA ) could enhance strength gains and improve body composition ( i.e. , increase fat-free mass ( FFM ) ; decrease body fat ) following  resistance exercise training in older adults ( > 65 y ) . Men ( N = 19 ) and women ( N = 20 ) completed six months of resistance exercise training with CrM (5g/d)+CLA ( 6g/d ) or placebo with r and omized , double blind , allocation . Outcomes included : strength and muscular endurance , functional tasks , body composition ( DEXA scan ) , blood tests ( lipids , liver function , CK , glucose , systemic inflammation markers ( IL-6 , C-reactive protein ) ) , urinary markers of compliance ( creatine/creatinine ) , oxidative stress ( 8-OH-2dG , 8-isoP ) and bone resorption ( Ν-telopeptides ) . Exercise training improved all measurements of functional capacity ( P<0.05 ) and strength ( P<0.001 ) , with greater improvement for the CrM+CLA group in most measurements of muscular endurance , isokinetic knee extension strength , FFM , and lower fat mass ( P<0.05 ) . Plasma creatinine ( P<0.05 ) , but not creatinine clearance , increased for CrM+CLA , with no changes in serum CK activity or liver function tests . Together , this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period . Trial Registration . Clinical Trials.gov The effect of duration -matched concurrent exercise training ( CET ) ( 50 % resistance ( RET ) and 50 % endurance ( EET ) training ) on physiological training outcomes in untrained middle-aged men remains to be eluci date d. Forty-seven men ( age , 48.1 ± 6.8 years ; body mass index , 30.4 ± 4.1 kg·m(-2 ) ) were r and omized into 12-weeks of EET ( 40 - 60 min of cycling ) , RET ( 10 exercises ; 3 - 4 sets × 8 - 10 repetitions ) , CET ( 50 % serial completion of RET and EET ) , or control condition . The following were determined : intervention-based changes in fitness and strength ; abdominal visceral adipose tissue ( VAT ) , total body fat ( TB-FM ) and fat-free ( TB-FFM ) mass ; plasma cytokines ( C-reactive protein ( CRP ) , tumor necrosis factor-α ( TNFα ) interleukin-6 ( IL-6 ) ) ; muscle protein content of p110α and glucose transporter 4 ( GLUT4 ) ; mRNA expression of GLUT4 , peroxisome proliferator-activated receptor-γ coactivator-1α-β , cytochrome c oxidase , hexokinase II , citrate synthase ; oral glucose tolerance ; and estimated insulin sensitivity . CET promoted commensurate improvements of aerobic capacity and muscular strength and reduced VAT and TB-FM equivalently to EET and RET ( p < 0.05 ) , yet only RET increased TB-FFM ( p < 0.05 ) . Although TNFα and IL-6 were reduced after all training interventions ( p < 0.05 ) , CRP remained unchanged ( p > 0.05 ) . EET reduced area under the curve for glucose , insulin , and C-peptide , whilst CET and RET respectively reduced insulin and C-peptide , and C-peptide only ( p < 0.05 ) . Notwithst and ing increased insulin sensitivity index after all training interventions ( p < 0.05 ) , no change presented for GLUT4 or p110α total protein , or chronic mRNA expression of the studied mitochondrial genes ( p > 0.05 ) . In middle-aged men , 12 weeks of duration -matched CET promoted commensurate changes in fitness and strength , abdominal VAT , plasma cytokines and insulin sensitivity , and an equidistant glucose tolerance response to EET and RET ; despite no change of measured muscle mechanisms associative to insulin action , glucose transport , and mitochondrial function Testosterone increases fat-free mass ( FFM ) in men infected with human immunodeficiency virus ( HIV ) , but its effects on muscle performance , physical function , mood , and quality of life are poorly understood . Sixty-one HIV-infected men with weight loss were r and omized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk . The primary outcome of interest was physical function ( walking speed , stair-climbing power , and load-carrying ability ) . Secondary outcome measures included body weight and composition , muscle performance , sexual function , mood , and quality of life . Serum nadir free and total testosterone levels increased ( + 188.0 + /- 29.6 and + 720 + /- 86 ng/dl ) in the testosterone , but not placebo , group . Testosterone administration was associated with increased FFM ( 2.8 + /- 0.5 kg ) , which was significantly greater than in the placebo group ( P < 0.0001 ) . Leg press strength increased significantly in testosterone-treated ( P = 0.027 ) , but not placebo-treated , men ; the difference between groups was not significant . Other measures of muscle performance and physical function did not change significantly in either group . Men receiving testosterone demonstrated significantly greater improvements in mental health and quality -of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo .  Sexual function scores did not change in either group . In HIV-infected men with weight loss , a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function . Improvements in mood , fatigue , and quality -of-life measures in the testosterone group , although clinical ly important , need further confirmation OBJECTIVES This study investigated the efficacy of Task-Related Training ( TRT ) Combined with Transcutaneous Electrical Nerve Stimulation ( TENS ) on the improvement of upper limb muscle activation in chronic stroke survivors with mild or moderate paresis . METHODS A single-blind , r and omized clinical trial was conducted with 46stroke survivors with chronic paresis . They were r and omly allocated two groups : the TRT+TENS group ( n = 23 ) and the TRT+ placebo TENS ( TRT+PLBO ) group ( n = 23 ) . The TRT+TENS group received 30 minutes of high-frequency TENS on wrist and elbow extensors , while the TRT+PLBO group received placebo TENS that was not real ES . Both groups did 30 minutes of TRT after TENS application . Intervention was given five days a week for four weeks . The primary outcomes of upper limb muscle activation were measured by integrated EMG ( IEMG ) , a digital manual muscle tester for muscle strength , active range of motion ( AROM ) and Fugl-Meyer Assessment of the upper extremity ( FMA-UE ) . The measurements were performed before and after the 4 weeks intervention period . RESULTS Both groups demonstrated significant improvements of outcomes in IEMG , AROM , muscle strength and FMA-UE during intervention period . When compared with the TRT+PLBO group , the TRT+TENS group showed significantly greater improvement in muscle activation ( wrist extensors , P = 0.045 ; elbow extensors , P = 0.004 ) , muscle strength ( wrist extensors , P = 0.044 ; elbow extensors , P = 0.012 ) , AROM ( wrist extension , P = 0.042 ; elbow extensors , P = 0.040 ) and FMA-UE ( total , P < 0.001 ; shoulder/elbow/forearm , P = 0.001 ; wrist , P = 0.002 ; coordination , P = 0.008 ) at the end of intervention . CONCLUSIONS Our findings indicate that TRT Combined with TENS can improve paretic muscle activity in upper limb paresis , highlighting the benefits of somatosensory stimulation from TENS 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 Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT )  were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits CONTEXT Cycling and rogens has been reported by athletes to improve physical performance by enhancing muscle mass and strength , a paradigm that has not been studied , and may have clinical value in older men being treated with testosterone .  OBJECTIVE We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current st and ard of care continuous therapy on body composition and muscle strength in older men . DESIGN , SETTING , AND PATIENTS Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were r and omized at the Institute for Translational Sciences- Clinical Research Center into a 5-month double-blind placebo-controlled trial . INTERVENTION Subjects were dosed weekly for 5 months , receiving continuous testosterone ( TE , n = 8 ; 100 mg testosterone enanthate , i m injection ) , monthly cycled testosterone ( MO , n = 8 ; alternating months of testosterone and placebo ) , or placebo ( PL , n = 8) . MAIN OUTCOME MEASURES Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength . Secondary outcomes included body weight , serum hormones , and mixed-muscle protein fractional synthesis rate ( FSR ) . RESULTS Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO ( P < 0.05 ) . Upper body muscle strength increased in TE , and lower body muscle strength increased in TE and MO ( P < 0.05 ) . FSR increased in TE and MO ( P < 0.05 ) but not in PL . CONCLUSIONS Cycled testosterone  improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone BACKGROUND Loss of muscle mass ( sarcopenia ) leads to frailty in older men . The decline in testosterone over the life span may contribute to this muscle loss . We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period . METHODS A st and ard dose ( 80 mg twice daily ) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older . All men had a free testosterone index of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . Measurements of body composition , muscle strength , hormones , and safety parameters were obtained at 0 , 6 , and 12 months . RESULTS Lean body mass increased ( p = .0001 ) and fat mass decreased ( p = .02 ) in the testosterone as compared with the placebo-treated group . There were no significant effects on muscle strength . There was a significant increase in hematocrit ( 0.02 % ) in the testosterone-treated group ( p = .03 ) . Plasma triglycerides , total cholesterol , and low-density lipoprotein cholesterol levels were similar in both groups , but there was a decrease in high-density lipoprotein cholesterol ( -0.1 mmol/L ) at 12 months in the testosterone group as compared to the placebo group ( p = 0.026 ) . There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups . CONCLUSION Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat BACKGROUND Progressive resistance exercise training ( PRT ) has been shown to increase muscle strength and fat-free mass ( FFM ) in elderly persons . Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons . METHODS Ninety-one community-dwelling sedentary men and women , 78 years and older with physical frailty ( defined using st and ardized objective criteria ) were enrolled in a 9-month trial of exercise training ( ET ) . Physical frailty was defined as having 2 of the 3 following criteria : modified Physical Performance Test score between 18 and 32 , peak aerobic power between 10 and 18 ml/kg/min , or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living . Participants were r and omly assigned to either a control ( CTL ) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT . RESULTS After completion of PRT , ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension ( mean Delta + 5.3 + /- 13 ft/lb vs + 1.1 + /- 11 ft/lb , p = .05 ) , measured using isokinetic dynamometry . Total body FFM ( measured using dual energy x-ray absorptiometry ) increased in the ET group , but not in the CTL group ( mean Delta + 0.84 + /- 1.4 kg vs + 0.01 + /- 1.5 kg , p = .005 ) . Total , trunk , intra-abdominal , and subcutaneous fat mass ( measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging ) did not change in response to PRT . CONCLUSIONS Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail , community-dwelling elderly women and men . This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population BACKGROUND Older adults supplemented for 1 year with β-hydroxy-β-methylbutyrate , arginine , and lysine ( HMB/ARG/LYS ) were previously shown to have significant gains in fat-free mass ( FFM ) but not muscular strength . OBJECTIVE Recently , increasing levels of serum vitamin D have been associated with an increase in muscle function , particularly in the elderly . To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS , the authors performed post hoc analysis of strength based on the participants ' vitamin D status . METHODS Elderly ( age 76.0 ± 1.6 years ) adults were recruited for a double-blinded , controlled study and were r and omly assigned to either an isonitrogenous control ( n = 37 ) or HMB/ARG/LYS ( n = 40 ) for the yearlong study . Participants were further segregated based on their vitamin D status of either < 30 or ≥30 ng 25OH-vitD(3)/mL serum , and an analysis was performed on the 4 cohorts . RESULTS Regardless of vitamin D status , HMB/ARG/LYS result ed in significantly increased FFM ( P < .02 ) , but only in those with vitamin D status ≥30 ng 25OH-vitD(3)/mL was there a significant increase in strength with HMB/ARG/LYS ( P < .01 ) . Control-supplemented participants , regardless of vitamin D status , and the HMB/ARG/LYS-supplemented participants with vitamin D status < 30 ng 25OH-vitD(3 ) failed to show improvements in strength . CONCLUSIONS The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status , but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and vitamin 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 PURPOSE To evaluate the effect of adding exercise to a hypocaloric diet on changes in appendicular lean mass and strength in frail obese older adults undergoing voluntary weight loss . METHODS Thirty frail older ( age , 70 + /- 5 yr ) obese ( body mass index , 37 + /- 5 kg.m ) adults were r and omly assigned to 6 months of diet/behavioral therapy ( diet group , n = 15 ) or diet or behavioral therapy plus exercise that incorporated progressive resistance training ( PRT ; diet + exercise group ; n = 15 ) . Body composition was assessed using dual-energy x-ray absorptiometry , and muscle strength was assessed using one-repetition maximum . The volume of upper extremity ( UE ) and lower extremity ( LE ) exercise training was determined by multiplying the average number of repetitions performed by the average weight lifted during the first three exercise sessions and during the last three exercise sessions of the study . RESULTS The diet and the diet + exercise groups had similar ( P > 0.05 ) decreases in weight ( 10.7 + /- 4.5 vs 9.7 + /- 4.0 kg ) and fat mass ( 6.8 + /- 3.7 vs 7.7 + /- 2.9 kg ) . However , the diet + exercise group lost less fat-free mass ( FFM ; 1.8 + /- 1.5 vs 3.5 + /- 2.1 kg ) , LE lean mass ( 0.9 + /- 0.8 vs 2.0 + /- 0.9 kg ) , and UE lean mass ( 0.1 + /- 0.2 vs 0.2 + /- 0.2 kg ) than the diet group ( P < 0.05 ) . The diet + exercise group had greater increases in percent of weight as FFM ( FFM / weight x 100 ) than the diet group ( 7.9 + /- 3.3 vs 5.4 + /- 3.7 % ; P < 0.05 ) . Despite lean mass losses , the diet + exercise group increased UE and LE strength in response to exercise ( 17 - 43 % ) , whereas the diet group maintained strength . The volume of UE and LE exercises correlated with the amount of UE and LE lean mass ( r = 0.64 - 0.84 ; P < 0.05 ) . CONCLUSION Exercise added to diet reduces muscle mass loss during voluntary weight loss and increases muscle strength in frail obese older adults . Regular exercise that incorporates PRT should be used to attenuate muscle mass loss in frail obese older adults on weight-loss therapy OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes ABSTRACT The purpose of this study was to examine the effect of a 12-week resistance training programme on fat-free mass ( FFM ) , muscle cross-sectional area , muscular strength and muscle quality in women who underwent Roux-en-Y gastric bypass surgery . Participants were 16 women ( mean age = 44.9 ± 10.2 years ) from bariatric surgical groups who were r and omly assigned into either a  control or an intervention group  . Air displacement plethysmography measured FFM and magnetic resonance imaging measured quadriceps muscle cross-sectional area and whole thigh muscle cross-sectional area . Muscular strength and quality was assessed using an estimated 1-Repetition Maximum assessment . All measurements were collected twice , at baseline and at a 12-week follow-up . There were significantly greater improvements in leg press strength ( mean differences = 55.4 % , P < 0.001 , Cohen ’s d = 2.4 ) , leg extension strength ( mean differences = 18.0 % , P = 0.014 , Cohen ’s d = 0.86 ) and leg press muscle quality ( mean differences = 54.5 % , P < 0.001 , Cohen ’s d = 1.9 ) in the intervention group compared to the control group following the resistance training programme . The resistance training intervention significantly improved muscular strength and quality ; however , it did not illicit changes in FFM or muscle cross-sectional area in women who underwent Roux-en-Y gastric bypass surgery The insulin resistance associated with aging may be due , in part , to reduced levels of physical activity in the elderly . We hypothesized that strength training increases insulin action in older individuals . To test this hypothesis , 11 healthy men 50 - 63 yr old [ mean 58 + /- 1 ( SE ) yr ] underwent a two-step hyperinsulinemic-euglycemic glucose clamp with concurrent indirect calorimetry and an oral glucose tolerance test ( OGTT ) before and after 16 wk of strength training . The training program increased overall strength by 47 % ( P < 0.001 ) . Fat-free mass ( FFM ; measured by hydrodensitometry ) increased ( 62.4 + /- 2.1 vs. 63.6 + /- 2.1 kg ; P < 0.05 ) and body fat decreased ( 27.2 + /- 1.8 vs. 25.6 + /- 1.9 % ; P < 0.001 ) with training . Fasting plasma glucose levels and glucose levels during the OGTT were not significantly lower after training . In contrast , fasting plasma insulin levels decreased ( 85 + /- 25 vs. 55 + /- 10 pmol/l ; P < 0.05 ) and insulin levels decreased ( P < 0.05 , analysis of variance ) during the OGTT . Glucose infusion rates during the hyperinsulinemic-euglycemic glucose clamp increased 24 % ( 13.5 + /- 1.7 vs. 16.7 + /- 2.2 mumol.kg FFM-1.min-1 ; P < 0.05 ) during the low ( 20 mU.m-2.min-1 ) insulin infusion and increased 22 % ( 55.7 + /- 3.3 vs. 67.7 + /- 3.9 mumol.kg FFM-1.min-1 ; P < 0.05 ) during the high ( 100 mU.m-2.min-1 ) insulin infusion . These increases were accompanied by a 40 % increase ( n = 7 ; P < 0.08 ) in nonoxidative glucose metabolism during the high insulin infusion . These results demonstrate that strength training increases insulin action and lowers plasma insulin levels in middle-aged and older men PURPOSE Lower-limb muscle weakness has often been reported in COPD , and contributes to exercise intolerance . Controversial information is available regarding upper-limb muscle adaptations and the influence of muscle wasting on muscle weakness . We investigated leg and arm muscle function in 59 stable COPD patients ( GOLD stage III ) with preserved fat-free mass ( FFM ) and in 28 patients with reduced FFM relative to age- and sex-matched healthy control subjects and studied the effects of 8 wk of whole-body exercise training . METHODS FFM was measured with bioelectrical impedance analysis .  Isokinetic quadriceps ( F-leg ) and biceps strength ( F-arm ) , as well as quadriceps ( E-leg ) and biceps endurance ( E-arm ) were determined with a Biodex dynamometer . Exercise training consisted of cycle ergometry , treadmill walking , weight training , and gymnastics during 5 d.wk . RESULTS F-leg ( 76.2 + /- 3.6 vs 118.2 + /- 6.3 N.m , P < 0.001 ) and F-arm ( 25.6 + /- 1.3 vs 38.1 + /- 2.1 N.m , P < 0.001 ) were significantly and similarly reduced in the COPD patient group compared with controls . Also , E-leg ( -2.13 + /- 0.12 vs -1.61 + /- 0.11 , P < 0.01 ) , but not E-arm ( -2.72 + /- 0.11 and -2.47 + /- 0.13 NS ) , was decreased in patients . F-leg ( 62.4 + /- 4.3 vs 82.8 + /- 4.7 N.m , P < 0.01 ) , but not F-arm or muscle endurance , was reduced in FFM-depleted compared with non-FFM-depleted patients . Whereas after training F-leg and E-leg significantly increased by 20 % in the whole COPD group , biceps muscle function remained unchanged . CONCLUSION Lower- and upper-limb muscle dysfunction was observed in COPD patients , irrespective of the presence of FFM depletion . Generalized muscle weakness suggests systemic muscular involvement , although the preserved arm endurance and the poor response of arm performance to exercise training is indicative for intrinsic differences in muscular adaptations between leg and arm muscles Hanson , ED , Srivatsan , SR , Agrawal , S , Menon , KS , Delmonico , MJ , Wang , MQ , and Hurley , BF . Effects of strength training on physical function : influence of power , strength , and body composition . J Strength Cond Res 23(9 ) : 2627 - 2637 , 2009-The purpose of this study was to determine ( a ) the effects of strength training ( ST ) on physical function and ( b ) the influence of strength , power , muscle volume ( MV ) , and body composition on physical function . Healthy , inactive adults ( n = 50 ) aged 65 years and older underwent strength , power , total body composition ( % fat and fat free mass [ FFM ] ) , and physical function testing before and after 22 weeks of ST . Physical function testing consisted of tasks design ed to mimic common physical activities of daily living ( ADL ) . To improve internal validity of the assessment of mid-thigh intermuscular fat , subcutaneous fat , and knee extensors MV , a 10-week unilateral ST program using the untrained leg as an internal control preceded 12 weeks of whole-body ST . Strength , power , and FFM increased significantly with ST ( all p < 0.05 ) , whereas rapid walk , 5 chair st and s , and get up and go time decreased significantly with ST in the overall group ( all p < 0.05 ) . Women improved significantly in both walking test times ( both p < 0.05 ) but not in the stair climb test , whereas men improved in the stair climb test ( p < 0.05 ) but not in walking test times . Multiple regression analysis revealed the highest R2 ( 0.28 ) for the change in chair st and s time , followed by stair climb and usual walk at 0.27 and 0.21 , respectively . ST improves performance in functional tasks important for ADLs . Changes in strength , power , and FFM are predictors of ST-induced improvements in these tasks The purpose of this study was to examine the effects of 10 weeks of aerobic endurance training ( AET ) , resistance exercise training ( RET ) , or a control ( CON ) condition on absolute and relative fat mass ( FM ) or fat-free mass ( FFM ) in the total body ( TB ) and regions of interest ( ROIs ) of sedentary overweight middle-aged males and females . Following prescreening , 102 subjects underwent anthropometric measurements , dual-energy X-ray absorptiometry , and strength and aerobic exercise testing . R and omized subjects ( male RET , n = 16 ; female RET , n = 19 ; male AET , n = 16 ; and female AET , n = 25 ) completed supervised and periodized exercise programs ( AET , 30 - 50 min cycling at 70%-75 % maximal heart rate ; RET , 2 - 4 sets × 8 - 10 repetitions of 5 - 7 exercises at 70%-75 % 1 repetition maximum ) or a nonexercising control condition ( male CON , n = 13 and female CON , n = 13 ) . Changes in absolute and relative TB-FM and TB-FFM and ROI-FM and ROI-FFM were determined . At baseline , and although matched for age and body mass index , males had greater strength , aerobic fitness , body mass , absolute and relative TB-FFM and ROI-FFM , but reduced absolute and relative TB-FM and ROI-FM , compared with females ( p < 0.05 ) . After training , both female exercise groups showed equivalent or greater relative improvements in strength and aerobic fitness than did the male exercise groups ( p < 0.05 ) ; however , the male exercise groups increased TB-FFM and reduced TB-FM more than did the female exercise groups ( p < 0.05 ) . Male AET altered absolute FM more than male RET altered absolute FFM , thus result ing in a greater enhancement of relative FFM . Despite equivalent or greater responses to RET or AET by female subjects , the corresponding respective increases in FFM or reductions in FM were lower than those in males , indicating that a biased dose-response relationship exists between sexes following 10 weeks of exercise training Limited data have suggested that the consumption of fluid milk after resistance training ( RT ) may promote skeletal muscle hypertrophy . The aim of this study was to assess whether a milk-based nutritional supplement could enhance the effects of RT on muscle mass , size , strength , and function in middle-aged and older men . This was an 18-mo factorial design ( r and omized control trial ) in which 180 healthy men aged 50 - 79 yr were allocated to the following groups : 1 ) exercise + fortified milk , 2 ) exercise , 3 ) fortified milk , or 4 ) control . Exercise consisted of progressive RT with weight-bearing impact exercise . Men assigned to the fortified milk consumed 400 ml/day of low-fat milk , providing an additional 836 kJ , 1000 mg calcium , 800 IU vitamin D(3 ) , and 13.2 g protein per day . Total body lean mass ( LM ) and fat mass ( FM ) ( dual-energy X-ray absorptiometry ) , midfemur muscle cross-sectional area ( CSA ) ( quantitative computed tomography ) , muscle strength , and physical function were assessed . After 18 mo , there was no significant exercise by fortified milk interaction for total body LM , muscle CSA , or any functional measure . However , main effect analyses revealed that exercise significantly improved muscle strength ( approximately 20 - 52 % , P < 0.001 ) , LM ( 0.6 kg , P < 0.05 ) , FM ( -1.1 kg , P < 0.001 ) , muscle CSA ( 1.8 % , P < 0.001 ) , and gait speed ( 11 % , P < 0.05 ) relative to no exercise . There were no effects of the fortified milk on muscle size , strength , or function . In conclusion , the daily consumption of low-fat fortified milk does not enhance the effects of RT on skeletal muscle size , strength , or function in healthy middle-aged and older men with adequate energy and nutrient intakes
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
BACKGROUND Inconsistent fat-free mass ( FFM ) and muscle strength responses have been reported in r and omized clinical trials ( RCTs ) administering  testosterone replacement therapy ( TRT ) to middle-aged and older men .
Our objective was to conduct a meta- analysis to determine whether TRT improves FFM and muscle strength in middle-aged and older men and whether the muscular responses vary by TRT administration route .