title: Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Effects of testosterone supplementation in the aging male. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. Effect of testosterone treatment on bone mineral density in men over 65 years of age. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middle-aged men. 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. 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. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. DHEA in elderly women and DHEA or testosterone in elderly men. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial.
abstract: Purpose . We performed a r and omised controlled study regarding the effects of and rogen replacement therapy ( ART ) on lower urinary tract symptoms ( LUTS ) in hypogonadal men with benign prostate hypertrophy ( BPH ) . Methods . Fifty-two patients with hypogonadism and BPH were r and omly assigned to receive testosterone ( ART group ) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group . We compared International Prostate Symptom Score ( IPSS ) , uroflowmetry data , post-voiding residual volume ( PVR ) and systemic muscle volume at baseline and 12 months after treatment . Results . Forty-six patients ( ART group , n = 23 ; control , n = 23 ) were included in the analysis . At the 12-month visit , IPSS showed a significant decrease compared with baseline in the ART group ( 15.7 ± 8.7 vs. 12.5 ± 9.5 ; p < 0.05 ) . No significant changes were observed in the control group . The ART group also showed improvement in maximum flow rate and voided volume ( p < 0.05 ) , whereas no significant improvements were observed in the controls . PVR showed no significant changes in either group . In addition , the ART group showed significant enhancement of mean muscle volume ( p < 0.05 ) , whereas no significant changes were seen in the controls . Conclusion . ART improved LUTS in hypogonadal men with mild BPH BACKGROUND Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) and prostatic enlargement . OBJECTIVE To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention ( AUR ) , BPH-related surgery , and BPH clinical progression over 4 yr in men at increased risk of progression . DESIGN , SETTING , AND PARTICIPANTS The Combination of Avodart and Tamsulosin ( CombAT ) study was a 4-yr , multicenter , r and omised , double-blind , parallel-group study in 4844 men > or = 50 yr of age with a clinical diagnosis of BPH , International Prostate Symptom Score > or = 12 , prostate volume > or = 30 cm(3 ) , prostate-specific antigen 1.5 - 10 ng/ml , and maximum urinary flow rate ( Q(max ) ) > 5 and < or = 15 ml/s with minimum voided volume > or = 125 ml . INTERVENTION Oral daily tamsulosin , 0.4 mg ; dutasteride , 0.5 mg ; or a combination of both . MEASUREMENTS The 4-yr primary end point was time to first AUR or BPH-related surgery . Secondary end points included BPH clinical progression , symptoms , Q(max ) , prostate volume , safety , and tolerability . RESULTS AND LIMITATIONS Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery . Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression . Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr . Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies , with the exception of an imbalance in the composite term of cardiac failure among the three study arms . The lack of placebo control is a study limitation . CONCLUSIONS The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement . CLINICAL TRIALS.GOV IDENTIFIER : NCT00090103 ( http://www . clinical trials.gov/ct2/show/NCT00090103 ) 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 Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population Older men , particularly those with low serum testosterone ( T ) levels , might benefit from T therapy to improve bone mineral density ( BMD ) and reduce fracture risk . Concerns exist , however , about the impact of T therapy on the prostate in older men . We hypothesized that the combination of T and finasteride ( F ) , a 5 alpha-reductase inhibitor , might increase BMD in older men without adverse effects on the prostate . Seventy men aged 65 yr or older , with a serum T less than 12.1 nmol/liter on two occasions , were r and omly assigned to receive one of three regimens for 36 months : T enanthate , 200 mg i m every 2 wk with placebo pills daily ( T-only ) ; T enanthate , 200 mg every 2 wk with 5 mg F daily ( T+F ) ; or placebo injections and pills ( placebo ) . Low BMD was not an inclusion criterion . We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry . Prostate-specific antigen ( PSA ) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate . Fifty men completed the 36-month protocol . By an intent-to-treat analysis including all men for as long as they contributed data , T therapy for 36 months increased BMD in these men at the lumbar spine [ 10.2 + /- 1.4 % ( mean percentage increase from baseline + /- SEM ; T-only ) and 9.3 + /- 1.4 % ( T+F ) vs. 1.3 + /- 1.4 % for placebo ( P < 0.001 ) ] and in the hip [ 2.7 + /- 0.7 % ( T-only ) and 2.2 + /- 0.7 % ( T+F ) vs. -0.2 + /- 0.7 % for placebo , ( P < or = 0.02 ) ] . Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip . After 6 months of therapy , urinary deoxypyridinoline ( a bone-resorption marker ) decreased significantly compared with baseline in both the T-only and T+F groups ( P < 0.001 ) but was not significantly reduced compared with the placebo group . Over 36 months , PSA increased significantly from baseline in the T-only group ( P < 0.001 ) . Prostate volume increased in all groups during the 36-month treatment period , but this increase was significantly less in the T+F group compared with both the T-only and placebo groups ( P = 0.02 ) . These results demonstrate that T therapy in older men with low serum T  increases vertebral and hip BMD over 36 months , both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men . In addition , the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy . These findings have important implication s for the prevention and treatment of osteoporosis in older men with low T levels 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 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 INTRODUCTION Male hypogonadism is a significant and growing problem that can be successfully treated with testosterone replacement therapy . A new formulation of testosterone gel ( 1.62 % ) was developed with increased viscosity , reduced volume of application , and increased skin permeation compared with other currently available testosterone gels . AIM To evaluate the efficacy and safety of titrated doses of 1.62 % testosterone gel after daily application to the skin of hypogonadal men for 182 days . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled study in hypogonadal men ( 234 active ; 40 placebo ) , 18 to 80 years of age with average serum total testosterone concentrations < 300 ng/dL and prostate-specific antigen < 2.5 ng/mL.  Topical testosterone gel ( 1.62 % ) , 1.25 g , 2.5 g , 3.75 g , and 5.0 g , or placebo gel was applied once daily to either upper arms/shoulders or abdomen . Dose adjustments were made on days 14 , 28 , and 42 . Main Outcome Measures . The percentage of subjects with serum total testosterone average concentrations ( C(av ) ) within the normal range of 300 - 1,000 ng/dL on study days 14 , 56 , 112 , and 182 . RESULTS Following titration , significantly ( P < 0.0001 ) more subjects receiving active treatment had testosterone C(av ) values ( range 81.6 % to 82.5 % ) within the eugonadal range compared with placebo ( range 28.6 % to 37.0 % ) on all study days . The 1.62 % gel was safe and well tolerated . CONCLUSIONS In this study , treatment with 1.62 % testosterone gel was safe and efficacious , result ing in an acceptable percentage of hypogonadal males achieving eugonadal serum testosterone levels As men age , their serum testosterone concentrations decrease , as do their bone densities . Because bone density is also low in hypogonadal men , we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months . We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment . Ninety-six men completed the entire 36-month protocol . The mean serum testosterone concentration in the men treated with testosterone increased from 367 + /- 79 ng/dL ( + /-SD ; 12.7 + /- 2.7 nmol/L ) before treatment to 625 + /- 249 ng/dL ( 21.7 + /- 8.6 nmol/L ; P < 0.001 ) at 6 months of treatment and remained at that level for the duration of the study . The mean bone mineral density of the lumbar spine increased ( P < 0.001 ) in both the placebo-treated ( 2.5 + /- 0.6 % ) and testosterone-treated ( 4.2 + /- 0.8 % ) groups , but the mean changes did not differ between the groups . Linear regression analysis , however , demonstrated that the lower the pretreatment serum testosterone concentration , the greater the effect of testosterone treatment on lumbar spine bone density from 0 - 36 months ( P = 0.02 ) . This analysis showed a minimal effect ( 0.9 + /- 1.0 % ) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL ( 13.9 nmol/L ) , but an increase of 5.9 + /- 2.2 % for a pretreatment testosterone concentration of 200 ng/dL ( 6.9 nmol/L ) . Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall , but did increase it in those men with low pretreatment serum testosterone concentrations 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 CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 BACKGROUND The role of sex hormones in the prevention of cognitive decline is uncertain . Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function . But , there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment . METHODS In this pilot study , 11 men ( mean age 80 + /- 5 years , range 73 - 87 years ) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl ( lower limit for adult normal range ) were r and omized to receive intramuscular testosterone ( 200 mg every 3 weeks ) or placebo for 12 weeks . Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex hormone binding globulin , estradiol , and estrone ) , Behave AD Question naire , Katz Activities of Daily Living , Geriatric Depression Scale , Digit Span , Clock Face Drawing , Clock Face Perception , Verbal Fluency , Trail-Making B , and International Prostate Symptom Score at baseline , 4 weeks , and 10 weeks . RESULTS All men completed the study . Total and bioavailable testosterone , estrone , and estradiol levels increased in men receiving testosterone , but no changes were detected in men receiving placebo . No significant changes were found in behavior following testosterone supplementation , nor was there evidence of change in depression or activities of daily living . No discernable changes were found in any of the cognitive tests . Symptoms of prostate hyperplasia remained unchanged in the testosterone ( 6.6 + 5.8 to 5.2 + 3.6 ; p = .39 ) and placebo ( 8.8 + 6.4 to 6.4 + 3.8 ; p = .15 ) groups , and prostate-specific antigen levels did not change significantly . CONCLUSION No significant changes in behavior , function , depression , or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment . This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors 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 CONTEXT The cause of declining testosterone ( T )  in aging men and their relationships with risk factors are unclear . OBJECTIVE The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men . DESIGN This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40 - 79 yr from a prospect i ve cohort study in eight European countries . RESULTS Four predictors were associated with distinct modes of altered function : 1 ) age : lower free T ( FT ; -3.12 pmol/liter.yr , P < 0.001 ) with raised LH , suggesting impaired testicular function ; 2 ) obesity : lower total T ( TT ; -2.32 nmol/liter ) and FT ( -17.60 pmol/liter ) for body mass index ( BMI ; > or = 25 to < 30 kg/m(2 ) ) and lower TT ( -5.09 nmol/liter ) and FT ( -53.72 pmol/liter ) for BMI 30 kg/m(2 ) or greater ( P < 0.001 - 0.01 , referent : BMI < 25 kg/m(2 ) ) with unchanged/decreased LH , indicating hypothalamus/pituitary dysfunction ; 3 ) comorbidity : lower TT ( -0.80 nmol/liter , P < 0.01 ) with unchanged LH in younger men but higher LH in older men ; and 4 ) smoking : higher SHBG ( 5.96 nmol/liter , P < 0.001 ) and LH ( 0.77 U/liter , P < 0.01 ) with increased TT ( 1.31 nmol/liter , P < 0.001 ) but not FT , compatible with a re setting of T-LH-negative feedback due to elevated SHBG . CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment . These changes are differentially linked to specific risk factors . Some risk factors operate independently of but others interact with age , in contributing to the T decline . These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men Testosterone undecanoate ( 160 mg/day ) or placebo was given orally in a double-blind fashion for 8 months to 23 middle-aged men without urinary tract symptoms . Testosterone was found to increase the mean prostate volume by 12 % ( P < .012 ) . The treatment suppressed the serum concentrations of sex-hormone-binding globulin and follicle stimulating hormone . The observed decrease in the mean serum concentration of luteinizing hormone was not statistically significant . The serum concentrations of prostate-specific antigen did not change as measured by two different well-vali date d immunometric assays . No changes in micturition habits or urine flow charts were reported 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 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 BACKGROUND Loss of muscle mass ( sarcopenia ) leads to frailty in older men . The decline in testosterone over the life span may contribute to this muscle loss . We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period . METHODS A st and ard dose ( 80 mg twice daily ) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older . All men had a free testosterone index of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . Measurements of body composition , muscle strength , hormones , and safety parameters were obtained at 0 , 6 , and 12 months . RESULTS Lean body mass increased ( p = .0001 ) and fat mass decreased ( p = .02 ) in the testosterone as compared with the placebo-treated group . There were no significant effects on muscle strength . There was a significant increase in hematocrit ( 0.02 % ) in the testosterone-treated group ( p = .03 ) . Plasma triglycerides , total cholesterol , and low-density lipoprotein cholesterol levels were similar in both groups , but there was a decrease in high-density lipoprotein cholesterol ( -0.1 mmol/L ) at 12 months in the testosterone group as compared to the placebo group ( p = 0.026 ) . There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups . CONCLUSION Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat BACKGROUND 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 ] . ) 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
target: Conclusions : This meta- analysis shows that regardless of the administration method , TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points
background: Background : Testosterone replacement therapy ( TRT ) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome .
  Urologists have been concerned about the possibility of TRT causing prostate cancer .
  The aim of this study was to assess the relationship between TRT and prostate cancer .