Effects of testosterone supplementation in the aging male. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. A double-blind, placebo-controlled, randomized clinical trial of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Testosterone therapy increased muscle mass and lipid oxidation in aging men Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Effect of testosterone treatment on bone remodelling markers and mineral density in obese dieting men in a randomized clinical trial Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial.
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 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 Despite partial and rogen deficiency , the safety and efficacy of  and rogen therapy in older men remains controversial because controlled studies of testosterone have given equivocal results . Human chorionic gonadotropin ( hCG ) can be conveniently and infrequently self-administered , and it increases not only circulating testosterone but also estradiol and other testicular steroids . We evaluated the efficacy and safety of 3 months of treatment with sc recombinant hCG ( r-hCG , Ovidrel ) on muscle mass , strength , mobility , and physical activity in ambulant , community-dwelling men more than 60 yr old having partial and rogen deficiency ( testosterone < or = 15 nmol/liter , twice ) . Forty eligible men ( mean age , 67 yr ; range , 60 - 85 yr ) were r and omized to receive r-hCG ( 5000 IU , 250 microg ) or placebo by twice weekly sc self-injection and were studied before treatment , monthly during treatment , and 1 month after treatment . All completed the study , and treatment groups were well matched . r-hCG significantly increased body weight ( approximately 1 kg ; P < 0.05 ) and lean body mass ( approximately 2 kg ; P < 0.001 ) and reduced fat mass ( approximately 1 kg , P < 0.05 ) . However , anthropometric measures of skinfold thickness ( biceps , triceps , subscapular , suprailiac ) and circumferences ( midarm , waist , hip , and midthigh ) , including the waist-hip ratio , did not change significantly . Shoulder and knee strength ( peak torque ) , as measured by isokinetic and isometric dynamometry , was not significantly increased , nor was physical activity ( accelerometry and Physical Activity Scale for Elderly self-report ) or gait and balance ( modified Guralnik and Frailty and Injuries : Cooperative Studies of Intervention Techniques performance batteries ) altered . Total and free testosterone and estradiol were markedly ( 150 % ; P < 0.001 ) and stably increased , whereas LH , FSH , and urea were significantly decreased . Testis volume was significantly decreased ( approximately 5 ml ; P < 0.05 ) . There were no significant changes in hemoglobin , osteocalcin , or prostate-specific antigen , and the International Prostate Symptom Score did not change . Three men developed nipple tenderness that did not progress to gynecomastia . We conclude that 3 months of treatment with twice weekly r-hCG demonstrates sustained and rogenic effects on hormones and muscle mass but has no effect on muscle strength or physical functioning 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 Serum testosterone levels decline significantly with aging . Testosterone supplementation to older men might beneficially affect the aging processes . OBJECTIVE To investigate the effect of testosterone supplementation on functional mobility , cognitive function , bone mineral density , body composition , plasma lipids , quality of life , and safety parameters in older men with low normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherl and s. INTERVENTION Participants were r and omly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months . MAIN OUTCOME MEASURES Functional mobility ( Stanford Health Assessment Question naire , timed get up and go test , isometric h and grip strength , isometric leg extensor strength ) , cognitive function ( 8 different cognitive instruments ) , bone mineral density of the hip and lumbar spine ( dual-energy x-ray absorptiometry scanning ) , body composition ( total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass ) , metabolic risk factors ( fasting plasma lipids , glucose , and insulin ) , quality of life ( Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules ) , and safety parameters ( serum prostate-specific antigen level , ultrasonographic prostate volume , International Prostate Symptom score , serum levels of creatinine , aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase , hemoglobin , and hematocrit ) . RESULTS A total of 207 men completed the study . During the study , lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength . Cognitive function and bone mineral density did not change . Insulin sensitivity improved but high-density lipoprotein cholesterol decreased ; by the end of the study , 47.8 % in the testosterone group vs 35.5 % in the placebo group had the metabolic syndrome ( P = .07 ) . Quality -of-life measures were no different except for one hormone-related quality -of-life measure that improved . No negative effects on prostate safety were detected . CONCLUSION Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N23688581 CONTEXT Physical frailty is associated with reduced muscle strength , impaired physical function , and quality of life .  Testosterone ( T ) increases muscle mass and strength in hypogonadal patients . It is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T. OBJECTIVE Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men , on muscle mass and strength , physical function , and quality of life . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled , parallel-group , single-center study . PARTICIPANTS PARTICIPANTS were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter . METHODS Two hundred seventy-four participants were r and omized to transdermal T ( 50 mg/d ) or placebo gel for 6 months . Outcome measures included muscle strength , lean and fat mass , physical function , and self-reported quality of life . RESULTS Isometric knee extension peak torque improved in the T group ( vs. placebo at 6 months ) , adjusted difference was 8.6 ( 95 % confidence interval , 1.3 - 16.0 ; P = 0.02 ) Newton-meters . Lean body mass increased and fat mass decreased significantly in the T group by 1.08 + /- 1.8 and 0.9 + /- 1.6 kg , respectively . Physical function improved among older and frailer men . Somatic and sexual symptom scores decreased with T treatment ; adjusted difference was -1.2 ( -2.4 to -0.04 ) and -1.3 ( -2.5 to -0.2 ) , respectively . CONCLUSIONS T treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition , quality of life , and physical function . Further investigations are warranted to extend these results 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 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 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 BACKGROUND Testosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia . This study was design ed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men . METHODS A subgroup of 30 intermediate-frail and frail elderly men ( 65 - 89 years ) with low to borderline-low testosterone levels were enrolled from a single-center r and omized , double-blind placebo-controlled trial . Participants received either a transdermal testosterone ( 50 mg ) or placebo gel daily for 6 months . Architecture ( muscle thickness , fascicle length , and pennation angle ) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment .  RESULTS Serum testosterone  increased from 11.6 ± 3.5 to 18.0 ± 8.1 nmol/L by 10 days after r and omization in the active group ( but not the placebo group ) and was maintained throughout the treatment period . Testosterone treatment result ed in a preservation of muscle thickness at 6 months while it decreased in the placebo group ( effect size 1.4 [ 95 % confidence interval = 0.3 - 2.5 ; p = .015 ] ) . There was no significant effect of treatment on fascicle length ( effect size 1.9 mm [ 95 % confidence interval = -1.2 to 5.0 mm ; p = .22 ] ) or pennation angle ( effect size 1.2 ° [ 95 % confidence interval = -1.3 to 3.7 ° ; p = .32 ] ) . CONCLUSIONS Testosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness . The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men This open , prospect i ve therapeutic trial studied the effects of regular moderate and rogen supplementation on bone mineral density in eugonadal men with established osteoporosis , and collected data on the safety of and rogen therapy used in this setting . 23 men , aged 34 - 73 years , with vertebral crush fractures and back pain , in whom secondary causes of osteoporosis had been excluded , were treated with fortnightly intramuscular injections of 250 mg testosterone esters ( Sustanon 250(R ) ) for 6 months . Blood pressure was recorded monthly ; fasting lipids , glucose , haematocrit , plasma viscosity , and testosterone levels were measured every 3 months . Psychological effects were assessed using the Hospital Anxiety and Depression Scale ( HADS ) and General Health Question naire ( GHQ ) , together with question ing on libido changes . Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry ( DEXA ) over the treatment period . 21 men completed the study period .  Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2 ) to 0.839 g/cm(2 ) during treatment ( p < 0 . 001 ) , a rise of 5 % in 6 months . Bone mineral density at the hip did not change . There were significant , favorable changes in diastolic blood pressure ( -4.7 mmHg , p < 0.01 ) , serum triglyceride levels ( -0.405 mmol/L , p < 0.01 ) , and total cholesterol ( -0.27 mmol/L , p < 0.05 ) . Adverse changes included a fall in HDL cholesterol ( -0.087 mmol/L , p < 0.05 ) and a rise in plasma viscosity which was significant at 3 months but not at 6 months . The expected rises in hematocrit ( 0.434 to 0.456 ) and FAI ( 0.504 to 0.887 ) occurred . We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis , without an overall adverse effect on cardiovascular risk factors . This treatment warrants further evaluation in a r and omized , controlled trial The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment .  Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( -3.96 % ) and body fat ( -5.65 % ) ; negligible changes were found in the control group . TU significantly improved metabolic control : decrease in blood glucose values and mean glycated hemoglobin ( HbA1c ) ( from 10.4 to 8.6 % ) . TU treatment significantly improved symptoms of and rogen deficiency ( including erectile dysfunction ) , with virtually no change in the control group . There were no adverse effects on blood pressure or hematological , biochemical and lipid parameters , and no adverse events . Oral TU treatment of type 2 diabetic men with and rogen deficiency  improves glucose homeostasis and body composition ( decrease in visceral obesity ) , and improves symptoms of and rogen deficiency ( including erectile dysfunction ) . In these men , the benefit of testosterone supplementation therapy exceeds the correction of symptoms of and rogen deficiency and also includes glucose homeostasis and metabolic control To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men , 100 obese men aged 53 years ( interquartile range 47–60 ) with a total testosterone level < 12 nmol/L receiving 10 weeks of a very low energy diet ( VLED ) followed by 46 weeks of weight maintenance were r and omly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate ( n = 49 , cases ) or matching placebo ( n = 51 , controls ) . Pre-specified outcomes were between-group differences ( mean adjusted difference , MAD ) in serum c-telopeptide ( CTx ) , N-terminal propeptide of type 1 procollagen ( P1NP ) and bone mineral density ( BMD ) . At trial end , CTx was significantly reduced in men receiving testosterone compared to placebo , MAD −66 ng/L ( 95 % CI −113 , −18 ) , p = 0.018 , and this was apparent already after the 10 week VLED phase , MAD −63 ng/L ( 95 % CI −108 , −18 ) , p = 0.018 . P1NP was marginally increased after VLED , MAD + 4.2 ug/L ( 95 % CI −0.01 , + 8.4 ) , p = 0.05 but lower at study end , MAD −5.6 ug/L ( 95 % CI −10.1 , −1.1 ) , p = 0.03 . No significant changes in sclerostin , lumbar spine BMD or femoral BMD were seen . We conclude that in obese men with low testosterone levels  undergoing weight loss , bone remodelling markers are modulated in a way that may have favourable effects on bone mass Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months .  Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men 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 BACKGROUND Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of  cardiovascular events in men r and omized to testosterone  , result ing in enrollment cessation by trial 's Data and Safety Monitoring Board . We evaluated changes in gonadal hormones and markers of inflammation and coagulation to eluci date risk factors associated with cardiovascular events . METHODS Men aged 65 years or more , 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 . Changes in total and free testosterone , estradiol and estrone , C-reactive protein , interleukin 6 , fibrinogen , plasminogen activator inhibitor-1 , and pro-brain naturetic peptide were compared between groups and within the testosterone group between subjects who experienced cardiovascular events and those who did not . RESULTS Of 209 men r and omized ( mean age 74 years ) , gonadal hormones and biomarkers were available in 179 men . Baseline body mass index , gonadal hormones , lipids , Framingham risk scores , and other biomarkers were similar in the two treatment groups . Within the testosterone group , the 6-month increase in free testosterone was significantly greater in men who experienced cardiovascular events than in those who did not [ mean ( 95 % confidence interval ) , 10.6 ( 4.6 - 16.7 ) vs 5.2 ( 3.0 - 7.5 ) ng/dL , p = .05 ] . In multivariable logistic regression analysis , the change in the serum levels of free testosterone was associated with cardiovascular events . CONCLUSION Mobility-limited older men who experienced cardiovascular events had greater increases in serum free testosterone levels than those who did not 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
The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men .
OBJECTIVES Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass , accumulation of central adiposity , impaired mobility and increased risk of bone fractures .
Whether and rogen treatment might be beneficial in these subjects is still under debate .
We have carried out a systematic review of r and omized controlled trials ( RCTs ) evaluating the effects of testosterone ( T ) administration  to middle-aged and ageing men on body composition , muscle strength , bone density , markers of bone metabolism and serum lipid profile .