title: Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. Effects of testosterone supplementation in the aging male. Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized‐controlled trial Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Testosterone therapy increased muscle mass and lipid oxidation in aging men Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. Development of a bedside viable ultrasound protocol to quantify appendicular lean tissue mass Androgen deprivation causes selective deficits in the biomechanical leg muscle function of men during walking: a prospective case–control study Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. Adverse events associated with testosterone administration. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men. Dual-energy X-ray absorptiometry lean soft tissue hydration: independent contributions of intra- and extracellular water. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. A population-level decline in serum testosterone levels in American men. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. Changes in muscle mass, muscle strength, and power but not physical function are related to testosterone dose in healthy older men. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. DHEA in elderly women and DHEA or testosterone in elderly men. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men.
abstract: 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 men receiving only testosterone for 24 weeks . LBM increased only in men receiving testosterone ( P = .004 ) . CONCLUSION Strength training in aging men with low-normal testosterone levels may improve mechanical muscle function , but this effect occurs without a significant increase in LBM . Clinical ly , only the combination of testosterone therapy and strength training result ed in an increase in mechanical muscle function and LBM Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer .  Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) < 70 ng/dL and fatigue score > 3/10 on the Edmonton Symptom Assessment Scale were eligible .  Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone  ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p < .002 ) at 12 months in the testosterone group , whereas no change occurred in the control group . Although there was no change in estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p < .017 ) . The testosterone group had a 0.3 % gain in femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia The indication for testosterone therapy in aging hypogonadal men without hypothalamic , pituitary , or testicular disease remains to be eluci date d. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity , substrate metabolism , body composition , and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone . A r and omized , double-blinded , placebo-controlled study of testosterone treatment ( gel ) was done on 38 men , aged 60–78 years , with bioavailable testosterone < 7.3 nmol/l and a waist circumference > 94 cm .  Insulin-stimulated glucose disposal ( Rd ) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry . Lean body mass ( LBM ) and total fat mass ( TFM ) were measured by dual x-ray absorptiometry , and serum total testosterone was measured by t and em mass spectrometry . Bioavailable testosterone was calculated . Coefficients ( b ) represent the placebo-controlled mean effect of intervention . LBM ( b = 1.9 kg , p = 0.003 ) increased while HDL – cholesterol ( b = −0.12 mmol/l , p = 0.043 ) and TFM decreased ( b = −1.2 kg , p = 0.038 ) in the testosterone group compared to placebo . Basal lipid oxidation ( b = 5.65 mg/min/m2 , p = 0.045 ) increased and basal glucose oxidation ( b = −9.71 mg/min/m2 , p = 0.046 ) decreased in response to testosterone therapy even when corrected for changes in LBM . No significant changes in insulin-stimulated Rd was observed ( b = −0.01mg/min/m2 , p = 0.92 ) . Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels ; however , our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique Long-term glucocorticoid therapy  in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone . We tested the effect of two and rogens , testosterone and its minimally aromatizable analog n and rolone , on muscle mass ( dual x-ray absorptiometry ) , muscle strength ( knee flexion and extension by isokinetic dynamometry ) , bone mineral density ( BMD ) , and quality of life ( Qualeffo-41 question naire ) in 51 men on a mean daily prednisone dose of 12.6 + /- 2.2 mg . Men were r and omized , double blind , to testosterone ( 200 mg mixed esters ) , n and rolone decanoate ( 200 mg ) , or placebo given every fortnight by i m injection for 12 months . At 12 months , both and rogens increased muscle mass ( mean change from baseline + 3.5 % , + 5.8 % , and -0.9 % in testosterone , n and rolone , and placebo groups , respectively , P < 0.0001 ) and muscle strength ( P < 0.05 ) . Lumbar spine BMD increased significantly only in men treated with testosterone ( 4.7 + /- 1.1 % , P < 0.01 ) . There was no significant change in hip or total body BMD . Testosterone , but not n and rolone or placebo , improved overall quality of life ( P < 0.001 ) . These results suggest that and rogen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for and rogen action on bone but not on muscle The pharmacokinetics , efficacy , and safety of the And roderm testosterone ( T ) transdermal system ( TTD ) and intramuscular T enanthate injections ( i.m . ) for the treatment of male hypogonadism were compared in a 24-week multicenter , r and omized , parallel-group study . Sixty-six adult hypogonadal men ( 22 - 65 years of age ) were withdrawn from prior i.m . treatment for 4 - 6 weeks and then r and omly assigned to treatment with TTD ( two 2.5-mg systems applied nightly ) or i.m . ( 200 mg injected every 2 weeks ) ; there were 33 patients per group . Twenty-six patients in the TTD group and 32 in the i.m . group completed the study .  TTD treatment produced circadian variations in the levels of total T , bioavailable T , dihydrotestosterone , and estradiol within the normal physiological ranges . i.m . treatment produced supraphysiological levels of T , bioavailable T , and estradiol ( but not dihydrotestosterone ) for several days after each injection . Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients ( range , 77 - 100 % ) than i.m . patients ( range , 19 - 84 % ) . Both treatments normalized LH levels in approximately 50 % of patients with primary hypogonadism ; however , LH levels were suppressed to the subnormal range in 31 % of i.m . patients vs. 0 % of TTD patients . Both treatments maintained sexual function ( assessed by question naire and Rigiscan ) and mood ( Beck Depression Inventory ) at the prior treatment levels . Prostate-specific antigen levels , prostate volumes , and lipid and serum chemistry parameters were comparable in both treatment groups . Transient skin irritation from the patches was reported by 60 % of the TTD patients , but caused only three patients ( 9 % ) to discontinue treatment . i.m . treatment produced local reactions in 33 % of patients and was associated with significantly more abnormal hematocrit elevations ( 43.8 % of patients ) compared with TTD treatment ( 15.4 % of patients ) . Gynecomastia resolved more frequently during TTD treatment ( 4 of 10 patients ) than with i.m . treatment ( 1 of 9 patients ) . Although both treatments seem to be efficacious for replacing T in hypogonadal men , the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over i.m . in minimizing excessive stimulation of erythropoiesis , preventing/ameliorating gynecomastia , and not over-suppressing gonadotropins CONTEXT Aging in men is associated with reduced testosterone ( T ) levels and physiological changes leading to frailty , but the benefits of T supplementation are inconclusive . OBJECTIVE We studied the effects of T supplementation with and without progressive resistance training ( PRT ) on functional performance , strength , and body composition . DESIGN , SETTING , AND PARTICIPANTS We recruited 167 generally healthy community-dwelling older men ( 66 ± 5 years ) with low-normal baseline total T levels ( 200 - 350 ng/dL ) . INTERVENTION Subjects were r and omized to placebo or transdermal T gel [ 2 doses targeting either a lower ( 400 - 550 ng/dL ) or higher ( 600 - 1000 ng/dL ) T range ] and to either PRT or no exercise for 12 months . MAIN OUTCOME MEASURE The primary outcome was functional performance , whereas secondary outcomes were strength and body composition . RESULTS A total of 143 men completed the study . At 12 months , total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group . In the PRT group , function and strength were not different between T- and placebo-treated subjects , despite greater improvements in fat mass ( P = .04 ) and fat-free mass ( P = .01 ) with T. In the non-PRT group , T did not improve function but improved fat mass ( P = .005 ) , fat-free mass ( P = .03 ) , and upper body strength ( P = .03 ) compared with placebo . There were fewer cardiovascular events in the T-treated groups compared with placebo . CONCLUSIONS T supplementation was well tolerated and improved body composition but had no effect on functional performance . T supplementation improved upper body strength only in nonexercisers compared with placebo Abstract Background Ultrasound is a non‐invasive and readily available tool that can be prospect ively applied at the bedside to assess muscle mass in clinical setting s. The four‐site protocol , which images two anatomical sites on each quadriceps , may be a viable bedside method , but its ability to predict musculature has not been compared against whole‐body reference methods . Our primary objectives were to ( i ) compare the four‐site protocol 's ability to predict appendicular lean tissue mass from dual‐energy X‐ray absorptiometry ; ( ii ) optimize the predictability of the four‐site protocol with additional anatomical muscle thicknesses and easily obtained covariates ; and ( iii ) assess the ability of the optimized protocol to identify individuals with low lean tissue mass . Methods This observational cross‐sectional study recruited 96 university and community dwelling adults . Participants underwent ultrasound scans for assessment of muscle thickness and whole‐body dual‐energy X‐ray absorptiometry scans for assessment of appendicular lean tissue . Ultrasound protocol s included ( i ) the nine‐site protocol , which images nine anterior and posterior muscle groups in supine and prone positions , and ( ii ) the four‐site protocol , which images two anterior sites on each quadriceps muscle group in a supine position . Results The four‐site protocol was strongly associated ( R 2 = 0.72 ) with appendicular lean tissue mass , but Bl and –Altman analysis displayed wide limits of agreement ( −5.67 , 5.67 kg ) . Incorporating the anterior upper arm muscle thickness , and covariates age and sex , alongside the four‐site protocol , improved the association ( R 2 = 0.91 ) with appendicular lean tissue and displayed narrower limits of agreement ( −3.18 , 3.18 kg ) . The optimized protocol demonstrated a strong ability to identify low lean tissue mass ( area under the curve = 0.89 ) . Conclusions The four‐site protocol can be improved with the addition of the anterior upper arm muscle thickness , sex , and age when predicting appendicular lean tissue mass . This optimized protocol can accurately identify low lean tissue mass , while still being easily applied at the bedside Abstract Background Although muscle mass declines with testosterone deficiency in men , previous studies of muscle function have not demonstrated consistent deficits , likely due to relatively insensitive methodology . Our objective was to determine the effects of testosterone deprivation on the biomechanical function of individual lower‐limb muscles . Methods We conducted a 12‐month prospect i ve , observational case – control study of 34 men newly commencing and rogen deprivation treatment ( ADT ) for prostate cancer and 29 age‐matched prostate cancer controls . Participants were assessed at 0 , 6 , and 12 months while walking in a biomechanics laboratory . We combined video‐based motion capture and ground reaction force data with computerized musculoskeletal modelling to assess the following primary outcomes : ( i ) peak joint torques at the hip , knee and ankle , and corresponding individual muscle forces ; ( ii ) individual muscle contributions to acceleration of the body 's centre of mass ; and ( iii ) walking speed , stride length , and step width . A linear mixed model was used to compare mean differences between groups . Results Compared with controls over 12 months , men receiving ADT had a mean reduction in total testosterone level from 14.1 to 0.4 nmol/L , and demonstrated more marked decreases in peak hip flexor torque by 14 % [ mean difference −0.11 N/kg ( −0.19 , −0.03 ) , P = 0.01 ] and peak knee extensor torque by 16 % [ −0.11 N/kg ( −0.20 , −0.02 ) , P = 0.02 ] of the initial mean value . Correspondingly , iliopsoas force decreased by 14 % ( P = 0.006 ) , and quadriceps force decreased by 11 % , although this narrowly missed statistical significance ( P = 0.07 ) . Soleus decreased contribution to forward acceleration of the body 's centre of mass by 17 % [ mean difference −0.17 m/s2 ( −0.29 , −0.05 ) , P < 0.01 ] . No significant changes between groups were observed in other joint torques or individual muscle contributions to acceleration of the body . Step width increased by 18 % [ mean adjusted difference 1.4 cm ( 0.6 , 27.4 ) , P = 0.042 ] in the ADT group compared with controls , with no change in stride length or walking speed . Conclusions Testosterone deprivation selectively decreases lower‐limb muscle function , predominantly affecting muscles that support body weight , accelerate the body forwards during walking , and mediate balance . Future exercise and pro‐myogenic interventional studies to mitigate ADT‐associated sarcopenia should target these deficits Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels Testosterone ( T ) therapy in older men with low serum T levels increases lean body mass and decreases fat mass . These changes might improve physical performance and strength ; however , it has not been established whether T therapy improves functional outcome in older men . Moreover , concerns exist about the impact of T therapy on the prostate in older men . The administration of finasteride ( F ) , which partially blocks the conversion of T to the more potent and rogen , dihydrotestosterone , attenuates the impact of T replacement on prostate size and prostate-specific antigen . We hypothesized that T replacement in older , hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance , strength , and body composition . Seventy men with low serum T ( < 350 ng/dl ) , age 65 yr and older , were r and omly assigned to receive one of three regimens for 36 months : 1 ) T enanthate , 200 mg i m every 2 wk , with placebo pills daily ( T-only ) ; 2 ) T enanthate , 200 mg every 2 wk , with 5 mg F daily ( T + F ) ; or 3 ) placebo injections and pills ( placebo ) . We obtained serial measurements of timed physical performance , grip strength , lower extremity strength , body composition ( by dual-energy x-ray absorptiometry ) , fasting cholesterol profiles , and hormones .  Fifty men completed the 36-month protocol . After 36 months , T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 + /- 1.6 % ( mean + /- sem , T-only ) and 3.8 + /- 1.0 % ( T + F ) vs. -5.6 + /- 1.9 % for placebo ( P < 0.002 for both T and T + F vs. placebo ) ] and increased h and grip strength compared with baseline and placebo ( P < 0.05 ) . T therapy increased lean body mass [ 3.77 + /- 0.55 kg ( T-only ) and 3.64 + /- 0.56 kg ( T + F ) vs. -0.21 + /- 0.55 kg for placebo ( P < 0.0001 ) ] , decreased fat mass , and significantly decreased total cholesterol , low-density lipoprotein , and leptin , without affecting high-density lipoprotein , adiponectin , or fasting insulin levels . These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months , when administered alone or when combined with F , and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men BACKGROUND Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men . The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied . METHODS Community-dwelling men , 65 years of age or older , with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter ( 3.5 to 12.1 nmol per liter ) or a free serum testosterone level of less than 50 pg per milliliter ( 173 pmol per liter ) were r and omly assigned to receive placebo gel or testosterone gel , to be applied daily for 6 months . Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification . The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group . RESULTS A total of 209 men ( mean age , 74 years ) were enrolled at the time the trial was terminated . At baseline , there was a high prevalence of hypertension , diabetes , hyperlipidemia , and obesity among the participants . During the course of the study , the testosterone group had higher rates of cardiac , respiratory , and dermatologic events than did the placebo group . A total of 23 subjects in the testosterone group , as compared with 5 in the placebo group , had cardiovascular-related adverse events . The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period . As compared with the placebo group , the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load . CONCLUSIONS In this population of older men with limitations in mobility and a high prevalence of chronic disease , the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events . The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy . ( Clinical Trials.gov number , NCT00240981 . We investigated the effects of 6 mo of near-physiological testosterone administration  to older men on skeletal muscle function and muscle protein metabolism .  Twelve older men ( > or = 60 yr ) with serum total testosterone concentrations < 17 nmol/l ( 480 ng/dl ) were r and omly assigned in double-blind manner to receive either placebo ( n = 5 ) or testosterone enanthate ( TE ; n = 7 ) injections . Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point . TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l . Lean body mass ( LBM ) , muscle volume , prostate size , and urinary flow were measured at baseline and at 6 mo . Protein expression of and rogen receptor ( AR ) and insulin-like growth factor I , along with muscle strength and muscle protein metabolism , were measured at baseline and at 1 and 6 mo of treatment . Hematological parameters were followed monthly throughout the study . Older men receiving  testosterone increased total and leg LBM , muscle volume , and leg and arm muscle strength after 6 mo . LBM accretion result ed from an increase in muscle protein net balance , due to a decrease in muscle protein breakdown . TE treatment increased expression of AR protein at 1 mo , but expression returned to pre-TE treatment levels by 6 mo . IGF-I protein expression increased at 1 mo and remained increased throughout TE administration . We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels .  Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure CONTEXT Declines in GH and testosterone ( Te ) secretion may contribute to the detrimental aging changes of elderly men . OBJECTIVE To assess the effects of near-physiological GH with/without Te administration on lean body mass , total body fat , midthigh muscle cross-section area , muscle strength , aerobic capacity , condition-specific quality of life ( Age-Related Hormone Deficiency-Dependent Quality of Life question naire ) , and generic health status ( 36-Item Short-Form Health Survey ) of older men . DESIGN , SETTING S , AND PARTICIPANTS A 6-month , r and omized , double-blind , placebo-controlled trial was performed on 80 healthy , community-dwelling , older men ( age , 65 - 80 yr ) . INTERVENTIONS Participants were r and omized to receive 1 ) placebo GH or placebo Te , 2 ) recombinant human GH ( rhGH ) and placebo Te ( GH ) , 3 ) Te and placebo rhGH ( Te ) , or 4 ) rhGH and Te ( GHTe ) . GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range . A fixed dose of Te ( 5 mg ) was given by transdermal patches . RESULTS Lean body mass increased with GHTe ( P = 0.008 ) and GH ( P = 0.004 ) , compared with placebo . Total body fat decreased with GHTe only ( P = 0.02 ) . Midthigh muscle ( P = 0.006 ) and aerobic capacity ( P < 0.001 ) increased only after GHTe . Muscle strength changes were variable ; one of six measures significantly increased with GHTe . Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life question naire score ( P = 0.007 ) in the GH and GHTe groups . Bodily pain increased with GH alone , as determined by the Short-Form Health Survey ( P = 0.003 ) . There were no major adverse effects . CONCLUSION Coadministration of low dose GH with Te result ed in beneficial changes being observed more often than with either GH or Te alone BACKGROUND Lower muscle mass has been correlated with poor physical function ; however , no studies have examined this relationship prospect ively . This study aims to investigate whether low muscle mass , low muscle strength , and greater fat infiltration into the muscle predict incident mobility limitation . METHODS Our study cohort included 3075 well-functioning black and white men and women aged 70 - 79 years participating in the Health , Aging , and Body Composition study . Participants were followed for 2.5 years . Muscle cross-sectional area and muscle tissue attenuation ( a measure of fat infiltration ) were measured by computed tomography at the mid-thigh , and knee extensor strength by using a KinCom dynamometer .  Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps . RESULTS Mobility limitations were developed by 22.3 % of the men and by 31.8 % of the women . Cox 's proportional hazards models , adjusting for demographic , lifestyle , and health factors , showed a hazard ratio of 1.90 [ 95 % confidence interval ( CI ) , 1.27 - 2.84 ] in men and 1.68 ( 95 % CI , 1.23 - 2.31 ) in women for the lowest compared to the highest quartile of muscle area ( p < .01 for trend ) . Results for muscle strength were 2.02 ( 95 % CI , 1.39 - 2.94 ) and 1.91 ( 95 % CI , 1.41 - 2.58 ) , p < .001 trend , and for muscle attenuation were 1.91 ( 95 % CI , 1.31 - 2.83 ) and 1.68 ( 95 % CI , 1.20 - 2.35 ) , p < .01 for trend . When included in one model , only muscle attenuation and muscle strength independently predicted mobility limitation ( p < .05 ) . Among men and women , associations were similar for blacks and whites . CONCLUSION Lower muscle mass ( smaller cross-sectional thigh muscle area ) , greater fat infiltration into the muscle , and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women . The association between low muscle mass and functional decline seems to be a function of underlying muscle strength Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Introduction : The clinical significance of low to low-normal testosterone ( T ) levels in men remains debated . Aim : To analyze the effects of raising serum T on lean body mass ( LBM ) , fat mass ( FM ) , total body mass , and health-related quality -of-life ( HRQoL ) . Methods : R and omized , double-blind , placebo-controlled study . Men , aged 50–80 years , with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L , and a Aging Males ’ Symptoms ( AMS ) total score > 36 , received 6 months treatment with transdermal 1 % T gel  ( 5–7.5 mg/day ; n = 183 ) or placebo gel ( n = 179 ) , followed by 12 months open-label with T in all . Results : After 6 months , LBM increased in T- treated patients by 1.28 ± 0.15 kg ( mean ± SE ) and FM decreased by 1.16 ± 0.16 kg , with minor changes with placebo ( LBM + 0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg ; all p < 0.001 , T group vs. placebo ) . Changes were largely similar across subgroups of age , baseline total testosterone , and baseline BMI . Total HRQoL improved compared with placebo ( p < 0.05 , T group vs. placebo ) . Conclusions : Six months 1 % T gel improved body composition and HRQoL  in symptomatic men with low to low-normal T , with further improvements over the following 12 months Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone < 10 nmol/L or free and rogen index < 30 % ) . Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD CONTEXT Symptoms of fluid retention in GH-deficient patients during GH replacement  are greater in men than in women , suggesting that testosterone may augment or estradiol may attenuate the antinatriuretic actions of GH . The mechanisms underlying the sodium-retaining effects of GH are poorly understood . AIM The aim of this study was to investigate the effects of GH and testosterone , alone and in combination , on extracellular water ( ECW ) and the hormonal mechanisms involved . DESIGN Two separate , open-label , r and omized , two-period , crossover studies were performed ; the first compared the effects of GH alone with those of GH and testosterone , and the second compared the effects of testosterone alone with those of GH and testosterone . PARTICIPANTS Twelve hypopituitary men with GH deficiency and hypogonadism were studied . INTERVENTION During the weeks of intervention , GH ( 0.5 mg/d ) and testosterone enanthate ( 250 mg ) were administered by i m injection . OUTCOME MEASURES The outcome measures were ECW , IGF-I , plasma renin activity ( PRA ) , aldosterone ( Aldo ) , and atrial natriuretic peptide ( ANP ) . RESULTS GH treatment significantly increased ( P < 0.05 ) both IGF-I and ECW , and these changes were enhanced by cotreatment with testosterone ( P = 0.07 for both ) . PRA , Aldo , and ANP levels did not change . Testosterone treatment alone did not change the IGF-I concentration , whereas cotreatment with GH induced a marked increase . Testosterone alone increased ( P < 0.05 ) ECW , and the effect was augmented ( P < 0.01 ) by cotreatment with GH . Although PRA and ANP did not change , plasma Aldo decreased after single and combined treatments . CONCLUSION GH and testosterone exerted independent and additive effects on ECW . The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules . This is the first direct evidence that testosterone increases ECW BACKGROUND Hypogonadism and anemia are common comorbid conditions in dialysis patients .  Testosterone replacement may improve such clinical parameters as anemia , sarcopenia , and low libido . Additionally , by increasing hemoglobin levels , testosterone replacement may allow for a dose reduction in recombinant human erythropoietin ( rHuEPO ) , thereby reducing cost . METHODS This phase IV , single-center , placebo-controlled , double-blind study assessed the effect of transdermal testosterone on serum testosterone levels , rHuEPO dose required to maintain hemoglobin level , bone mineral content , lean body mass and fat content , cholesterol level , sexual function , and mood . Forty hypogonadal male hemodialysis patients who were administered rHuEPO were r and omly assigned to 100 mg of topical 1 % testosterone gel ( Testim ; Auxilium Pharmaceuticals , Norristown , PA ) or placebo , applied daily for 6 months . RESULTS Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL ( < 10.4 nmol/L ) participated in this trial . In men assigned to administration of transdermal testosterone , there was an increase beyond that in the placebo group in mean serum testosterone ( 77.1 ng/dL [ 2.7 nmol/L ] ) , dihydrotestosterone ( DHT ; 0.8 nmol/L ) , and estradiol levels ( 6.3 pg/mL [ 23.0 pmol/L ] ) and a decrease in mean serum luteinizing hormone levels ( -3.1 IU/L ) . Compared with subjects administered placebo , participants on testosterone replacement therapy did not show an appreciable change in  rHuEPO dose ( mean difference adjusted for baseline values , 12.6 U/kg/wk ; P = 0.73 ) , bone mineral density , lean body mass or fat content , cholesterol level , sexual function , or mood . CONCLUSION Daily administration of 100 mg of topical 1 % testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease . Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study . Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol .  Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo  , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone .  Hypogonadism was defined as a bioavailable testosterone < 60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory .  Testosterone improved bilateral grip strength ( P < 0.05 by ANOVA ) and increased hemoglobin ( P < 0.001 by ANOVA ) . The men assigned to testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P < 0.02 ) . There were no significant changes in prostate-specific antigen or memory .  Three subjects receiving placebo and seven subjects receiving  testosterone  withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit .  Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men .  Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks OBJECTIVE One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging . In this study , we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency . DESIGN Double-blind , placebo-controlled r and omized study ( testosterone ) , and additional r and omization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency . METHODS Seventy sedentary , community dwelling men were r and omized to a 5 mg testoderm transdermal system applied daily vs placebo system , and additionally r and omized to a home-based resistance exercise program . Subjects were r and omized to Group 1 ( testosterone plus exercise ) , Group 2 ( testosterone plus no exercise ) , Group 3 ( placebo plus exercise ) , and Group 4 ( placebo plus no exercise ) . Endpoints included quality of life ( assessed by the short form-36 question naire ) and body composition ( measured by dual x-ray absorptiometry scan ) . RESULTS Serum testosterone  increased by a mean of 10.0 + /- 1.9 , 6.6 + /- 1.6 , 0.52 + /- 0.6 , and 0.5 + /- 0.6 nmol/l in Groups 1 , 2 , 3 , and 4 respectively . There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning ( P = 0.03 ) , role physical ( P = 0.01 ) , general health ( P = 0.049 ) , and social functioning ( P = 0.04 ) . There were no effects of testosterone or exercise on quality of life alone , nor in body composition parameters . CONCLUSIONS Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program . The combination of testosterone and exercise may be an important strategy in the elderly , though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well Dual-energy X-ray absorptiometry ( DEXA ) provides a measure of lean soft tissue ( LST ) . LST hydration , often assumed to be constant , is relevant to several aspects of DEXA body composition estimates . The aims of this study were to develop a theoretical model of LST total body water ( TBW ) content and to examine hydration effects with empirically derived model coefficients and then to experimentally test the model 's prediction that , in healthy adults , LST hydration is not constant but varies as a function of extra- and intracellular water distribution ( E/I ) . The initial phase involved TBW/LST model development and application with empirically derived model coefficients . Model predictions were then tested in a cross-sectional study of 215 healthy adults .  LST was measured by DEXA , extracellular water ( ECW ) by NaBr dilution , intracellular water ( ICW ) by whole body (40)K counting , and TBW by (2)H(2)O dilution .  TBW estimates , calculated as ECW + ICW , were highly correlated with ( r = 0.97 , SEE = 2.1 kg , P < 0.001 ) and showed no significant bias compared with TBW measured by (2)H(2)O. Model-predicted TBW/LST was almost identical to experimentally derived values ( means + /- SD ) in the total group ( 0.767 vs. 0.764 + /- 0.028 ) . LST hydration was significantly correlated with E/I ( total group , r = 0.30 , SEE = 0.027 , P < 0.001 ) . Although E/I increased with age ( men , r = 0.48 ; women , r = 0.37 ; both P < 0.001 ) , the association between TBW/LST and age was nonsignificant . Hydration of the DEXA-derived LST compartment is thus not constant but varies predictably with ECW and ICW distribution . This observation has implication s for the accuracy of body fat measurements by DEXA and the use of TBW as a means of checking DEXA system calibration Muscle wasting in older men may be related to and rogen deficiency . We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older ( age > 60 years ) men with blood testosterone levels < 14 nmol/L. Subjects ( n = 7 per group ) received testosterone enanthate 200 mg i.m . or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks . A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group . Total body mass , haemoglobin and packed cell volume also increased significantly ( p < 0.05 ) . No improvements in h and grip strength , isometric strength of knee flexors and extensors or leg extensor power were seen in either group . Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function Testosterone ( T ) in a hydroalcoholic gel has been developed as an effective and convenient open system for transdermal delivery of the hormone to men . Because the gel can be applied either to small or large areas of skin , it was important to assess whether the skin surface area on which the gel was applied was an important determinant of serum T levels . To answer this question , the pharmacokinetics of a transdermal 1 % hydroalcoholic gel preparation of T was studied in nine hypogonadal men . The subjects applied in r and om order a 25-mg metered dose of T gel either four times at one site ( left arm/shoulder ) or at four different sites ( left and right arms/shoulders and left and right abdomen ) once daily ( 6 - 8 min ) for 7 consecutive days . After 7 days of washout , each subject was then crossed over to the opposite regimen for another 7 days of treatment . Serum sample s were collected for measurements of T , 5alpha dihydrotestosterone ( DHT ) , and estradiol before , during ( days 1 , 2 , 3 , 5 , and 7 ) , and after ( days 8 , 9 , 11 , 13 , and 15 ) application of T gel . Multiple blood sample s were drawn on the 1st and 7th day after gel application ; single sample s were obtained just before the next T gel application on other days ( 24 h after the previous gel application ) . The T gel dried in less than 5 min , left no residue , and produced no skin irritation in any of the subjects . Mean serum T levels , irrespective of application at one site or four sites followed the same pattern : rising to 2- to 3- and 4- to 5-fold above baseline at 0.5 and 24 h after first application , respectively . Thereafter , serum T levels reached steady state and remained at 4- to 5-fold above baseline ( at the upper limit of the normal adult range ) for the duration of gel application and returned to baseline within 4 days after stopping application . The application of T gel at four sites ( application skin area approximately four times that of one site ) result ed in a mean area under the curve ( AUC0 - 24h ) for serum T levels on the 7th day ( 868 + /- 72 nmol*h/L , mean + /- SEM ) , which was 23 % higher but not significantly different ( P = 0.06 ) than repeated application at one site ( 706 + /- 59 nmol*h/L ) . This could be due to the limited number of subjects studied ( n = 9 ) .  Mean serum DHT levels followed the same pattern as serum T , achieving steady-state levels by 2 days . The mean concentration of serum DHT on the 7th day was significantly higher after application at four sites ( 9.15 + /- 1.26 nmol/L , P < 0.05 ) than at one site ( 6.9 + /- 0.77 nmol/L ) . These serum DHT levels were at or above the normal adult male range . Serum DHT : T ratio was not significantly altered by T gel application . Serum estradiol levels followed the same pattern as serum T and showed no significant difference between the one- or four-site application . We conclude that transdermal daily application of 100 mg T gel result ed in similar steady levels of serum T. The surface area of the skin to which the gel was applied had only a modest impact on serum T and DHT levels . Mean serum levels of T and DHT was higher by 23 % and 33 % , respectively , despite application of the gel to four times the skin area in the four sites compared with the one site group . Because of the greater dosage flexibility provided , hydroalcoholic T gel application over multiple sites seems to be an effective and nonskin-irritating method of transdermal T delivery for hypogonadal men . Dose-ranging studies are required to determine dosage regimens for T gel application as a replacement therapy in hypogonadal men CONTEXT Age-specific estimates of mean testosterone ( T ) concentrations appear to vary by year of observation and by birth cohort , and estimates of longitudinal declines in T typically outstrip cross-sectional decreases . These observations motivate a hypothesis of a population -level decrease in T over calendar time , independent of chronological aging . OBJECTIVE The goal of this study was to establish the magnitude of population -level changes in serum T concentrations and the degree to which they are explained by secular changes in relative weight and other factors . DESIGN We describe a prospect i ve cohort study of health and endocrine functioning in r and omly selected men of age 45 - 79 yr . We provide three data collection waves : baseline ( T1 : 1987 - 1999 ) and two follow-ups ( T2 : 1995 - 1997 , T3 : 2002 - 2004 ) . SETTING This was an observational study of r and omly selected men residing in greater Boston , Massachusetts . PARTICIPANTS Data obtained from 1374 , 906 , and 489 men at T1 , T2 , and T3 , respectively , totaling 2769 observations taken on 1532 men . MAIN OUTCOME MEASURES The main outcome measures were serum total T and calculated bioavailable T. RESULTS We observe a substantial age-independent decline in T that does not appear to be attributable to observed changes in explanatory factors , including health and lifestyle characteristics such as smoking and obesity . The estimated population -level declines are greater in magnitude than the cross-sectional declines in T typically associated with age . CONCLUSIONS These results indicate that recent years have seen a substantial , and as yet unrecognized , age-independent population -level decrease in T in American men , potentially attributable to birth cohort differences or to health or environmental effects not captured in observed data 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 In the present cross-sectional study of 403 independently living elderly men , we tested the hypothesis that the decreases in bone mass , body composition , and muscle strength with age are related to the fall in circulating endogenous testosterone ( T ) and estrogen concentrations . We compared various measures of the level of bioactive and rogen and estrogen to which tissues are exposed . After exclusion of subjects with severe mobility problems and signs of dementia , 403 healthy men ( age , 73 - 94 yr ) were r and omly selected from a population -based sample .  Total T ( TT ) , free T ( FT ) , estrone ( E1 ) , estradiol ( E2 ) , and sex hormone-binding globulin ( SHBG ) were determined by RIA . Levels of non-SHBG-bound T ( non-SHBG-T ) , FT ( calc-FT ) , the TT/SHBG ratio , non-SHBG-bound E2 , and free E2 were calculated . Physical characteristics of aging included muscle strength measured using dynamometry , total body bone mineral density ( BMD ) , hip BMD , and body composition , including lean mass and fat mass , measured by dual-energy x-ray absorptiometry . In this population of healthy elderly men , calc-FT , non-SHBG-T , E1 , and E2 ( total , free , and non-SHBG bound ) decreased significantly with age . T ( total and non-SHBG-T ) was positively related with muscle strength and total body BMD ( for non-SHBG-T , respectively , beta = 1.93 + /- 0.52 , P < 0.001 and beta = 0.011 + /- 0.002 , P < 0.001 ) . An inverse association existed between T and fat mass ( beta = -0.53 + /- 0.15 , P < 0.001 ) . Non-SHBG-T and calc-FT were more strongly related to muscle strength , BMD , and fat mass than TT and were also significantly related to hip BMD . E1 and E2 were both positively , independently associated with BMD ( for E2 , beta = 0.21 + /- 0.08 , P < 0.01 ) . Non-SHBG-bound E2 was slightly strongly related to BMD than total E2 . The positive relation between T and BMD was independent of E2 . E1 and E2 were not related with muscle strength or body composition . In summary , bioavailable T , E1 , total E2 , and bioavailable E2 all decrease with age in healthy old men . In this cross-sectional study in healthy elderly men , non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T , which seems to play a direct role in the various physiological changes that occur during aging . A positive relation with muscle strength and BMD and a negative relation with fat mass was found . In addition , both serum E1 and E2 seem to play a role in the  age-related bone loss in elderly men , although the cross-sectional nature of the study precludes a definitive conclusion . Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD OBJECTIVES To examine the effect of grade d doses of testosterone on physical function and muscle performance in healthy , older men . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING General clinical research center . PARTICIPANTS Community-dwelling healthy men aged 60 to 75 ( N=44 ) . INTERVENTION Monthly treatment with a gonadotropin-releasing hormone agonist plus 25 , 50 , 125 , or 300 mg/wk of intramuscular injections of testosterone enanthate for 20 weeks . MEASUREMENTS Skeletal muscle mass ( SMM ) was estimated using dual-energy X-ray absorptiometry . Leg press strength was measured by one repetition maximum , leg power by Nottingham Leg Rig , and muscle fatigability by repetitions to failure in the leg press exercise .  Stair climbing , 6-meter and 400-meter walking speed , and a timed-up- and -go ( TUG ) test were used to assess physical function . RESULTS Significant testosterone dose- and concentration-dependent increases were observed in SMM ( P<.001 ) and maximal strength ( P=.001 ) but not muscle fatigability . Leg power also increased dose-dependently ( P=.048 ) . In contrast , changes in self-selected normal and fast walking speed over 6 or 400 meters , stair climbing power , and time for the TUG were not significantly related to testosterone dose , testosterone concentrations , or changes in muscle strength or power , or SMM . CONCLUSION Testosterone administration was associated with dose-dependent increases in SMM , leg strength , and power but did not improve muscle fatigability or physical function . The observation that physical function scores did not improve linearly with strength suggests that these high-functioning older men were already in the asymptotic region of the curve describing the relationship between physical function and strength CONTEXT Hormone administration to elderly individuals can increase lean body mass ( LBM ) and decrease fat , but interactive effects of growth hormone ( GH ) and sex steroids and their influence on strength and endurance are unknown . OBJECTIVE To evaluate the effects of recombinant human GH and /or sex steroids on body composition , strength , endurance , and adverse outcomes in aged persons . DESIGN , SETTING , AND PARTICIPANTS A 26-week r and omized , double-blind , placebo-controlled parallel-group trial in healthy , ambulatory , community-dwelling US women ( n = 57 ) and men ( n = 74 ) aged 65 to 88 years recruited between June 1992 and July 1998 . INTERVENTIONS Participants were r and omized to receive GH ( starting dose , 30 micro g/kg , reduced to 20 micro g/kg , subcutaneously 3 times/wk ) + sex steroids ( women : transdermal estradiol , 100 micro g/d , plus oral medroxyprogesterone acetate , 10 mg/d , during the last 10 days of each 28-day cycle [ HRT ] ; men : testosterone enanthate , biweekly intramuscular injections of 100 mg ) ( n = 35 ) ; GH + placebo sex steroid ( n = 30 ) ; sex steroid + placebo GH ( n = 35 ) ; or placebo GH + placebo sex steroid ( n = 31 ) in a 2 x 2 factorial design . MAIN OUTCOME MEASURES Lean body mass , fat mass , muscle strength , maximum oxygen uptake ( VO(2)max ) during treadmill test , and adverse effects . RESULTS In women , LBM increased by 0.4 kg with placebo , 1.2 kg with HRT ( P = .09 ) , 1.0 kg with GH ( P = .001 ) , and 2.1 kg with GH + HRT ( P<.001 ) . Fat mass decreased significantly in the GH and GH + HRT groups . In men , LBM increased by 0.1 kg with placebo , 1.4 kg with testosterone ( P = .06 ) , 3.1 kg with GH ( P<.001 ) , and 4.3 kg with GH + testosterone ( P<.001 ) . Fat mass decreased significantly with GH and GH + testosterone . Women 's strength decreased in the placebo group and increased nonsignificantly with HRT ( P = .09 ) , GH ( P = .29 ) , and GH + HRT ( P = .14 ) . Men 's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone ( P = .05 ) . Women 's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH ( P = .07 ) and GH + HRT ( P = .06 ) . Men 's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone ( P = .49 ) but increased with GH ( P = .11 ) and with GH + testosterone ( P<.001 ) . Changes in strength ( r = 0.355 ; P<.001 ) and in VO(2)max ( r = 0.320 ; P = .002 ) were directly related to changes in LBM . Edema was significantly more common in women taking GH ( 39 % vs 0 % ) and GH + HRT ( 38 % vs 0 % ) . Carpal tunnel symptoms were more common in men taking GH + testosterone ( 32 % vs 0 % ) and arthralgias were more common in men taking GH ( 41 % vs 0 % ) . Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH ( P = .006 ) . CONCLUSIONS In this study , GH with or without sex steroids in healthy , aged women and men increased LBM and decreased fat mass .  Sex steroid + GH increased muscle strength marginally and VO ( 2)max in men , but women had no significant change in strength or cardiovascular endurance . Because adverse effects were frequent ( importantly , diabetes and glucose intolerance ) , GH interventions in the elderly should be confined to controlled studies BACKGROUND Dehydroepi and rosterone ( DHEA ) and testosterone are widely promoted as antiaging supplements , but the long-term benefits , as compared with potential harm , are unknown . METHODS We performed a 2-year , placebo-controlled , r and omized , double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA . Among the men , 29 received DHEA , 27 received testosterone , and 31 received placebo . Among the women , 27 received DHEA and 30 received placebo . Outcome measures included physical performance , body composition , bone mineral density ( BMD ) , glucose tolerance , and quality of life . RESULTS As compared with the change from baseline to 24 months in the placebo group , subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter ( 9.2 micromol per liter ) in men and by 3.8 microg per milliliter ( 10.3 micromol per liter ) in women . Among men who received testosterone , the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter ( 1.1 nmol per liter ) , as compared with the change in the placebo group . A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements . Neither hormone altered the peak volume of oxygen consumed per minute , muscle strength , or insulin sensitivity . Men who received testosterone had a slight increase in fat-free mass , and men in both treatment groups had an increase in BMD at the femoral neck . Women who received DHEA had an increase in BMD at the ultradistal radius . Neither treatment improved the quality of life or had major adverse effects . CONCLUSIONS Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition , physical performance , insulin sensitivity , or quality of life . ( Clinical Trials.gov number , NCT00254371 [ Clinical Trials.gov ] . ) OBJECTIVES This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity , ventilatory efficiency , muscle strength , insulin resistance , and baroreflex sensitivity ( BRS ) in elderly patients with chronic heart failure ( CHF ) . BACKGROUND CHF is characterized by a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function that could be involved in the pathophysiology of heart failure . METHODS Seventy elderly patients with stable CHF-median age 70 years , ejection fraction 31.8 + /- 7%-were r and omly assigned to receive testosterone ( n = 35 , intramuscular injection every 6 weeks ) or placebo ( n = 35 ) , both on top of optimal medical therapy . At baseline and at the end of the study , all patients underwent echocardiogram , cardiopulmonary exercise test , 6-min walk test ( 6MWT ) , quadriceps maximal voluntary contraction ( MVC ) , and isokinetic strength ( peak torque ) and BRS assessment ( sequences technique ) . RESULTS Baseline peak oxygen consumption ( VO(2 ) ) and quadriceps isometric strength showed a direct relation with serum testosterone concentration . Peak VO(2 ) significantly improved in testosterone but was unchanged in placebo .  Insulin sensitivity was significantly improved in testosterone . The MVC and peak torque significantly increased in testosterone but not in placebo . The BRS significantly improved in testosterone but not in placebo . Increase in testosterone levels was significantly related to improvement in peak VO(2 ) and MVC . There were no significant changes in left ventricular function either in testosterone or placebo . CONCLUSIONS These results suggest that long-acting testosterone therapy improves exercise capacity , muscle strength , glucose metabolism , and BRS in men with moderately severe CHF .  Testosterone benefits seem to be mediated by metabolic and peripheral effects OBJECTIVES To investigate the effects of testosterone supplementation on bone , body composition , muscle , physical function , and safety in older men . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING A major medical institution . PARTICIPANTS One hundred thirty-one men ( mean age 77.1 + /- 7.6 ) with low testosterone , history of fracture , or bone mineral density ( BMD ) T-score less than -2.0 and frailty . INTERVENTION Participants received 5 mg/d of testosterone or placebo for 12 to 24 months ; all received calcium ( 1500 mg/d diet and supplement ) and cholecalciferol ( 1,000 IU/d ) . MEASUREMENTS BMD of hip , lumbar spine , and mid-radius ; body composition ; sex hormones , calcium-regulating hormones ; bone turnover markers ; strength ; physical performance ; and safety parameters . RESULTS Ninety-nine men ( 75.6 % ) completed 12 months , and 62 ( 47.3 % ) completed end therapy ( mean 23 months ; range 16 - 24 months for 62 who completed therapy ) . Study adherence was 54 % , with 40 % of subjects maintaining 70 % or greater adherence . Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL , respectively , in the treatment group . BMD on testosterone  increased 1.4 % at the femoral neck and 3.2 % at the lumbar spine ( P=.005 ) and decreased 1.3 % at the mid-radius ( P<.001 ) . There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance . There were no differences in safety parameters . CONCLUSION Older , frail men receiving  testosterone replacement increased testosterone levels and had favorable changes in body composition , modest changes in axial BMD , and no substantial changes in physical function 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
target: 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: 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 .