human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT 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 Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range . Recently , a transdermal therapeutic system ( TTS ) for the delivery of testosterone was developed which , when applied to the scrotum , provides smooth serum testosterone levels . Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day . In all patients serum testosterone and dihydrotestosterone ( DHT ) determined 3 - 5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period . The DHT/testosterone ratio remained constant . In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals . In these patients serum testosterone levels in the physiological range were seen during the entire observation period , whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase . All patients in the 14-month treatment study were clinical ly well substituted and responded with good compliance . Clinical chemistry showed no abnormalities during treatment . Thus , the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism 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 During testosterone ( T ) therapy , T is partly converted to 17beta-estradiol ( E2 ) and 5alpha-dihydrotestosterone ( DHT ) . Effects of age , testosterone dose , and body composition on total and free E2 and DHT levels are unknown . OBJECTIVE We evaluated age and dose-related differences in E2 and DHT levels in response to grade d doses of testosterone enanthate in young and older men . METHODS Fifty-one young ( aged 19 - 35 yr ) and 52 older ( aged 59 - 75 yr ) men completed treatment with monthly injections of a GnRH agonist plus r and omly assigned weekly doses of testosterone enanthate ( 25 , 50 , 125 , 300 , or 600 mg ) for 5 months . RESULTS During testosterone administration , total and free E2 levels increased dose-dependently ( dose effect , P<0.001 ) in both young and older men . Total and free E2 levels and E2:T ratios during T administration were higher in older than young men , but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels , percentage fat mass , and SHBG . DHT levels and DHT : T ratios were dose-related but did not differ between young and older men . Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics . The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5alpha-reductase , independent of age . The Vmax parameter for E2 was 40 % higher in older men than younger men , but Vmax for DHT was not significantly different between age groups . CONCLUSIONS During i m testosterone administration , E2 and DHT levels exhibit saturable increases with dose . The rate of whole body aromatization is higher in older men , partly related to their higher percentage fat mass , SHBG , and testosterone levels Background : No r and omized study exists comparing the effects of different modes of and rogen substitution on bone mineral density ( BMD ) . Methods : We performed a prospect i ve , r and omized , trial assigning 53 hypogonadal men to the following treatment groups : mesterolone 100 mg p.o . daily , testosterone undecanoate 160 mg p.o . daily , testosterone enanthate 250 mg i.m . every 21 days , or a single subcutaneous implantation of 1,200 mg crystalline testosterone .  The BMD was determined by peripheral quantitative computed tomography . Results : At baseline , men with secondary hypogonadism ( n = 33 ) had a lower BMD ( –1.52 ± 0.23 SDS ; Z-scores ) than men with primary hypogonadism ( n = 20 , –0.87 ± 0.23 SDS , p < 0.01 ) . In men with primary hypogonadism , the BMD increased dose dependently ( crystalline testosterone + 7.0 ± 1.3 % , testosterone enanthate + 4.8 ± 0.2 % , testosterone undecanoate + 3.4 ± 2.5 % , mesterolone + 0.8 ± 1.6 % ) after 6 months of therapy . Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD . Conclusions : In primary hypogonadal men the BMD responds dose dependently to testosterone substitution , whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD Background . The beneficial effects of testosterone treatment ( TT ) are debated . Methods . Double-blinded , placebo-controlled study of six months TT ( gel ) in 54 men aged 60–78 with bioavailable testosterone ( BioT ) < 7.3 nmol/L and waist > 94 cm r and omized to TT ( 50–100 mg/day , n = 20 ) , placebo ( n = 18 ) , or strength training ( ST ) ( n = 16 ) for 24 weeks . Moreover , the ST group was r and omized to TT ( n = 7 ) or placebo ( n = 9 ) after 12 weeks . Outcomes . Chemokines ( MIF , MCP-1 , and MIP-1α ) and lean body mass ( LBM ) , total , central , extremity , visceral , and subcutaneous ( SAT ) fat mass established by DXA and MRI . Results . From 0 to 24 weeks , MIF and SAT decreased during ST + placebo versus placebo , whereas BioT and LBM were unchanged . TT decreased fat mass ( total , central , extremity , and SAT ) and increased BioT and LBM versus placebo . MIF levels increased during TT versus ST + placebo . ST + TT decreased fat mass ( total , central , and extremity ) and increased BioT and LBM versus placebo . From 12 to 24 weeks , MCP-1 levels increased during TT versus placebo and MCP-1 levels decreased during ST + placebo versus placebo . Conclusion . ST + placebo was associated with decreased MIF levels suggesting decreased inflammatory activity . TT may be associated with increased inflammatory activity . This trial is registered with Clinical Trials.gov NCT00700024 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 . O 
    Output:
    
agent
Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT 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 Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range . Recently , a transdermal therapeutic system ( TTS ) for the delivery of testosterone was developed which , when applied to the scrotum , provides smooth serum testosterone levels . Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day . In all patients serum testosterone and dihydrotestosterone ( DHT ) determined 3 - 5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period . The DHT/testosterone ratio remained constant . In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals . In these patients serum testosterone levels in the physiological range were seen during the entire observation period , whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase . All patients in the 14-month treatment study were clinical ly well substituted and responded with good compliance . Clinical chemistry showed no abnormalities during treatment . Thus , the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism 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 During testosterone ( T ) therapy , T is partly converted to 17beta-estradiol ( E2 ) and 5alpha-dihydrotestosterone ( DHT ) . Effects of age , testosterone dose , and body composition on total and free E2 and DHT levels are unknown . OBJECTIVE We evaluated age and dose-related differences in E2 and DHT levels in response to grade d doses of testosterone enanthate in young and older men . METHODS Fifty-one young ( aged 19 - 35 yr ) and 52 older ( aged 59 - 75 yr ) men completed treatment with monthly injections of a GnRH agonist plus r and omly assigned weekly doses of testosterone enanthate ( 25 , 50 , 125 , 300 , or 600 mg ) for 5 months . RESULTS During testosterone administration , total and free E2 levels increased dose-dependently ( dose effect , P<0.001 ) in both young and older men . Total and free E2 levels and E2:T ratios during T administration were higher in older than young men , but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels , percentage fat mass , and SHBG . DHT levels and DHT : T ratios were dose-related but did not differ between young and older men . Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics . The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5alpha-reductase , independent of age . The Vmax parameter for E2 was 40 % higher in older men than younger men , but Vmax for DHT was not significantly different between age groups . CONCLUSIONS During i m testosterone administration , E2 and DHT levels exhibit saturable increases with dose . The rate of whole body aromatization is higher in older men , partly related to their higher percentage fat mass , SHBG , and testosterone levels Background : No r and omized study exists comparing the effects of different modes of and rogen substitution on bone mineral density ( BMD ) . Methods : We performed a prospect i ve , r and omized , trial assigning 53 hypogonadal men to the following treatment groups : mesterolone 100 mg p.o . daily , testosterone undecanoate 160 mg p.o . daily , testosterone enanthate 250 mg i.m . every 21 days , or a single subcutaneous implantation of 1,200 mg crystalline testosterone .  The BMD was determined by peripheral quantitative computed tomography . Results : At baseline , men with secondary hypogonadism ( n = 33 ) had a lower BMD ( –1.52 ± 0.23 SDS ; Z-scores ) than men with primary hypogonadism ( n = 20 , –0.87 ± 0.23 SDS , p < 0.01 ) . In men with primary hypogonadism , the BMD increased dose dependently ( crystalline testosterone + 7.0 ± 1.3 % , testosterone enanthate + 4.8 ± 0.2 % , testosterone undecanoate + 3.4 ± 2.5 % , mesterolone + 0.8 ± 1.6 % ) after 6 months of therapy . Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD . Conclusions : In primary hypogonadal men the BMD responds dose dependently to testosterone substitution , whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD Background . The beneficial effects of testosterone treatment ( TT ) are debated . Methods . Double-blinded , placebo-controlled study of six months TT ( gel ) in 54 men aged 60–78 with bioavailable testosterone ( BioT ) < 7.3 nmol/L and waist > 94 cm r and omized to TT ( 50–100 mg/day , n = 20 ) , placebo ( n = 18 ) , or strength training ( ST ) ( n = 16 ) for 24 weeks . Moreover , the ST group was r and omized to TT ( n = 7 ) or placebo ( n = 9 ) after 12 weeks . Outcomes . Chemokines ( MIF , MCP-1 , and MIP-1α ) and lean body mass ( LBM ) , total , central , extremity , visceral , and subcutaneous ( SAT ) fat mass established by DXA and MRI . Results . From 0 to 24 weeks , MIF and SAT decreased during ST + placebo versus placebo , whereas BioT and LBM were unchanged . TT decreased fat mass ( total , central , extremity , and SAT ) and increased BioT and LBM versus placebo . MIF levels increased during TT versus ST + placebo . ST + TT decreased fat mass ( total , central , and extremity ) and increased BioT and LBM versus placebo . From 12 to 24 weeks , MCP-1 levels increased during TT versus placebo and MCP-1 levels decreased during ST + placebo versus placebo . Conclusion . ST + placebo was associated with decreased MIF levels suggesting decreased inflammatory activity . TT may be associated with increased inflammatory activity . This trial is registered with Clinical Trials.gov NCT00700024 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 . O 
    Output:
    