Testosterone Treatment of Men With Mild Cognitive Impairment and Low Testosterone Levels Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose–response randomized trial Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. Preliminary Clinical Experience with Androgen Administration for Pre- and Postmenopausal Women with Hypoactive Sexual Desire Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo 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. Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up Effect of Testosterone Administration on Sexual Behavior and Mood in Men with Erectile Dysfunction Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. Testosterone dose-response relationships in healthy young men.
Introduction : This study investigated the effects of testosterone ( T ) treatment on cognition , mood , and quality of life in men with mild cognitive impairment ( MCI ) and low serum T levels . Methods : A total of 351 community-dwelling men were screened , and 37 men evidence d both MCI and low T of whom 27 agreed for further screening . Twenty-two met all the study inclusion /exclusion criteria and enrolled in a 6-month r and omized , double-blind , placebo-controlled study . Results : Total T levels significantly increased in the T treatment group . No significant changes were observed in measures of cognition , mood , or quality of life other than improvement in 1 objective measure of verbal memory ( P < .05 ) and decreased depression symptoms ( P < .02 ) in the treatment group . Conclusions : Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low BACKGROUND This study assessed the feasibility of a 12-week program of exercise , with and without intramuscular testosterone supplementation , in male patients with chronic heart failure ( CHF ) and low testosterone status and collected preliminary data for key health outcomes . METHODS Male patients with CHF ( n = 41 , age 67.2 years , range 51 - 84 years ) with mean ± SD testosterone levels of 10.7 ± 2.6 nmol/L ( 309 ± 76 ng/dL ) were r and omly allocated to exercise with testosterone or placebo groups . Feasibility was assessed in terms of recruitment , intervention compliance , and attrition . Outcomes included an incremental shuttle walk test , peak oxygen uptake , muscular strength , echocardiographic measures , N-terminal pro-brain natriuretic peptide , inflammatory markers , depression ( Beck Depression Inventory ) , and health-related quality of life ( Minnesota Living with Heart Failure Question naire and Medical Outcomes Study Short-Form ) . RESULTS Attrition was 30 % but with 100 % compliance to exercise and injections in patients who completed the study . Similar improvements in shuttle walk test ( 18 % vs 19 % ) , body mass ( -1.3 kg vs -1.0 kg ) , and h and grip strength ( 2.1 kg vs 2.5 kg ) from baseline were observed in both groups . The exercise with testosterone group showed improvements from baseline in peak oxygen uptake ( P < .01 ) , Beck Depression Inventory ( P < .05 ) , leg strength ( P < .05 ) , and several Medical Outcomes Study Short-Form quality of life domains ( P < .05 ) , which were generally not apparent in the exercise with placebo group . Echocardiographic measures , N-terminal pro-brain natriuretic peptide , and inflammatory markers were mostly unchanged . CONCLUSIONS This study shows for the first time that testosterone supplementation during a program of exercise rehabilitation is feasible and can positively impact on a range of key health outcomes in elderly male patients with CHF who have a low testosterone status CONTEXT Serum concentrations of gonadal hormones have been associated with various measures of well-being , but it is unclear whether their association with mood is confounded by concurrent physical morbidity . OBJECTIVE To determine whether the association between serum testosterone concentration and mood in older men is independent of physical comorbidity . DESIGN Cross-sectional study . SETTING Community of Perth , Western Australia . PARTICIPANTS A community sample of men aged 71 to 89 years . MAIN OUTCOME MEASURES We used the 15-item Geriatric Depression Scale ( GDS-15 ) to assess depressed mood . Clinical ly significant depression was defined a priori as a GDS-15 score of 7 or greater . Physical health was assessed using the weighted Charlson index and the Physical Component Summary score of the 36-Item Short Form Health Survey . RESULTS Of 3987 men included in the study , 203 ( 5.1 % ; 95 % confidence interval [ CI ] , 4.4%-5.8 % ) had depression . Participants with depression had significantly lower total and free testosterone concentrations than nondepressed men ( P < .001 for both ) . However , they were also more likely to smoke and to have low educational attainment , a body mass index categorized as obese , a Mini-Mental State Examination score less than 24 , a history of antidepressant drug treatment , and greater concurrent physical morbidity . After adjusting for these factors and for age , men with depression were 1.55 ( 95 % CI , 0.91 - 2.63 ) and 2.71 ( 95 % CI , 1.49 - 4.93 ) times more likely to have total and free testosterone concentrations , respectively , in the lowest quintile . CONCLUSIONS A free testosterone concentration in the lowest quintile is associated with a higher prevalence of depression , and this association can not be adequately explained by physical comorbidity . A r and omized controlled trial is required to determine whether the link between low free testosterone level and depression is causal because older men with depression may benefit from systematic screening of free testosterone concentration and testosterone supplementation Testosterone ( T ) therapy in older men with low serum T levels increases lean body mass and decreases fat mass . These changes might improve physical performance and strength ; however , it has not been established whether T therapy improves functional outcome in older men . Moreover , concerns exist about the impact of T therapy on the prostate in older men . The administration of finasteride ( F ) , which partially blocks the conversion of T to the more potent and rogen , dihydrotestosterone , attenuates the impact of T replacement on prostate size and prostate-specific antigen . We hypothesized that T replacement in older , hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance , strength , and body composition . Seventy men with low serum T ( < 350 ng/dl ) , age 65 yr and older , were r and omly assigned to receive one of three regimens for 36 months : 1 ) T enanthate , 200 mg i m every 2 wk , with placebo pills daily ( T-only ) ; 2 ) T enanthate , 200 mg every 2 wk , with 5 mg F daily ( T + F ) ; or 3 ) placebo injections and pills ( placebo ) . We obtained serial measurements of timed physical performance , grip strength , lower extremity strength , body composition ( by dual-energy x-ray absorptiometry ) , fasting cholesterol profiles , and hormones .  Fifty men completed the 36-month protocol . After 36 months , T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 + /- 1.6 % ( mean + /- sem , T-only ) and 3.8 + /- 1.0 % ( T + F ) vs. -5.6 + /- 1.9 % for placebo ( P < 0.002 for both T and T + F vs. placebo ) ] and increased h and grip strength compared with baseline and placebo ( P < 0.05 ) . T therapy increased lean body mass [ 3.77 + /- 0.55 kg ( T-only ) and 3.64 + /- 0.56 kg ( T + F ) vs. -0.21 + /- 0.55 kg for placebo ( P < 0.0001 ) ] , decreased fat mass , and significantly decreased total cholesterol , low-density lipoprotein , and leptin , without affecting high-density lipoprotein , adiponectin , or fasting insulin levels . These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months , when administered alone or when combined with F , and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men CONTEXT Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation . Trial 's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm . The changes in muscle performance and physical function were evaluated in relation to participant 's perception of change . METHODS Men aged 65 years and older , with mobility limitation , total testosterone 100 - 350 ng/dL , or free testosterone less than 50 pg/mL , were r and omized to placebo or 10 g testosterone gel daily for 6 months . Primary outcome was leg-press strength . Secondary outcomes included chest-press strength , stair-climb , 40-m walk , muscle mass , physical activity , self-reported function , and fatigue . Proportions of participants exceeding minimally important difference in study arms were compared . RESULTS Of 209 r and omized participants , 165 had follow-up efficacy measures . Mean ( SD ) age was 74 ( 5.4 ) years and short physical performance battery score 7.7 ( 1.4 ) .  Testosterone arm exhibited greater improvements in leg-press strength , chest-press strength and power , and loaded stair-climb than placebo . Compared with placebo , significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths ( 43 % vs 18 % , p = .01 ) and stair-climbing power ( 28 % vs 10 % , p = .03 ) more than minimally important difference . Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass . Physical activity , walking speed , self-reported function , and fatigue did not change . CONCLUSIONS Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power . Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population Purpose To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels . Methods 71 hysterectomized women with or without oophorectomy with total testosterone < 31 ng/dl and /or free testosterone < 3.5 pg/ml received a st and ardized transdermal estradiol regimen during the 12-week run-in period and were then r and omized to receive weekly intramuscular injections of placebo , 3 , 6.25 , 12.5 , or 25 mg testosterone enanthate for 24 weeks .  Total testosterone  was measured in serum by LC – MS/MS , and free testosterone levels were measured by equilibrium dialysis .  Cognitive function was evaluated using a comprehensive battery of st and ardized neuropsychological tests at baseline and 24 weeks . Results 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample . The five groups were similar at baseline . Mean on-treatment nadir total testosterone concentrations were 15 , 89 , 98 , 134 , and 234 ng/dl in the placebo , 3 , 6.25 , 12.5 , and 25 mg groups , respectively . No significant changes in spatial ability , verbal fluency , verbal memory , or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function , age , and education . Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores . ConclusionS hort-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function Testosterone ( T ) levels decline as men age , but it is unclear whether this has an effect on cognition . Some studies indicate that lower T levels are associated with memory loss ; thus , maintaining a higher T level could have positive effects on aspects of cognitive function . Concerns exist , however , about the effect of T therapy on the prostate in older men . We hypothesized that T replacement in older men with low T levels would improve aspects of cognitive function and that the addition of finasteride would not affect the T-induced cognitive improvements .  Healthy men , 65 to 83 years of age , with baseline total T below 350 ng/dL and no evidence of cognitive impairment were r and omly assigned to 1 of 3 regimens : 200 mg of T every 2 weeks by intramuscular injection with placebo pill daily ( T-only ) , 200 mg of T every 2 weeks by intramuscular injection with 5 mg of finasteride daily ( T+F ) , or placebo injections and pills ( placebo ) . Sixty-nine men completed baseline cognitive testing ; 65 completed at least 4 months , and 46 completed all 36 months of the study . Participants were given a battery of cognitive evaluations at baseline , 4 months , and 36 months , along with measurement of serum hormone levels . Serum total T , bioavailable T , and estradiol levels in the T-only and T+F groups significantly increased throughout the treatment period , whereas these hormone levels did not change in the placebo group . Only minimally significant differences were seen among the 3 groups in any evaluation of cognitive performance , either in the short-term ( 4 months ) or the long-term ( 36 months ) analysis . These results indicate that T replacement , whether given alone or in combination with finasteride , for 36 months in healthy older men without cognitive impairment at baseline has no clinical ly significant effect on tests of cognitive function . Further studies are warranted to determine whether hormone replacement in men with preexisting cognitive impairment is beneficial Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT )  were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits 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 The present study examined effects of testosterone on  hypoactive sexual desire in pre- and postmenopausal women ( treated ) compared with an age-matched reference group ( reference ) . Treated participants received 100 mg of testosterone cypionate in oil injected intramuscularly ( i.m . ) monthly for 3 months . We measured salivary testosterone and scores on the Sexual Desire Inventory pretreatment and posttreatment . Treated and reference participants ' baseline testosterone was equivalent , however , treated participants exhibited higher testosterone levels than did reference participants posttreatment . As expected , treated participants exhibited lower baseline sexual desire than did reference participants and showed a significant increase in sexual desire posttreatment . This research suggests that testosterone may effectively alleviate hypoactive sexual desire , even in women with normal testosterone levels AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels .  Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure CONTEXT 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 This study prospect ively examined changes in cognition in hypogonadal men given testosterone ( T ) or older hypogonadal men given dihydrotestosterone ( DHT ) gel .  A battery of cognitive tests assessing verbal and spatial memory , language , and attention was administered at baseline ( prior to medication ) and again at days 90 and 180 of treatment for men receiving T gel and at baseline and days 30 and 90 of treatment for men receiving DHT gel . For men receiving T gel , circulating total T and estradiol ( E(2 ) ) were significantly raised compared with baseline , and a significant improvement in verbal memory was observed . For men receiving DHT gel , serum DHT levels increased and T levels decreased significantly compared with baseline , and a significant improvement in spatial memory was observed . The results suggest that beneficial changes in cognition can occur in hypogonadal men using T replacement levels and DHT treatment , and these changes in cognition can be reliably measured during a relative steady-state dose level . Further , our results suggest that aromatization of T to E(2 ) may regulate verbal memory in men , whereas nonaromatizable and rogens may regulate spatial memory Introduction : The clinical significance of low to low-normal testosterone ( T ) levels in men remains debated . Aim : To analyze the effects of raising serum T on lean body mass ( LBM ) , fat mass ( FM ) , total body mass , and health-related quality -of-life ( HRQoL ) . Methods : R and omized , double-blind , placebo-controlled study . Men , aged 50–80 years , with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L , and a Aging Males ’ Symptoms ( AMS ) total score > 36 , received 6 months treatment with transdermal 1 % T gel  ( 5–7.5 mg/day ; n = 183 ) or placebo gel ( n = 179 ) , followed by 12 months open-label with T in all . Results : After 6 months , LBM increased in T- treated patients by 1.28 ± 0.15 kg ( mean ± SE ) and FM decreased by 1.16 ± 0.16 kg , with minor changes with placebo ( LBM + 0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg ; all p < 0.001 , T group vs. placebo ) . Changes were largely similar across subgroups of age , baseline total testosterone , and baseline BMI . Total HRQoL improved compared with placebo ( p < 0.05 , T group vs. placebo ) . Conclusions : Six months 1 % T gel improved body composition and HRQoL  in symptomatic men with low to low-normal T , with further improvements over the following 12 months This double-blind placebo controlled , cross-over study was carried out to assess the effect of testosterone administration on sexual behavior mood , and psychological symptoms in healthy men with erectile dysfunction . Biweekly injections of 200 mg of testosterone enanthate were given over a period of 6 weeks separated by a washout period of 4 weeks . Blood sample s for hormonal assessment , behavioral and psychological ratings were obtained prior to each injection . Luteinizing hormone remained significantly depressed but circulating testosterone had returned to baseline levels by 2 weeks following each hormonal injection . The ejaculatory frequency during the testosterone phase was statistically higher than during the placebo phase . There were marked , although statistically nonsignificant , increases in median frequency of reported sexual desire , masturbation , sexual experiences with partner , and sleep erections during the testosterone period . Testosterone did not have demonstrable effects on ratings of penile rigidity and sexual satisfaction . Mood variables and psychological symptoms did not change following hormonal administration . Results suggest that and rogen administration to eugonadal men with erectile dysfunction may activate their sexual behavior without enhancing erectile capacity and without effects on mood and psychological symptoms 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 Testosterone increases muscle mass and strength and regulates other physiological processes , but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various and rogen-dependent processes are similar . To determine the effects of grade d doses of testosterone on body composition , muscle size , strength , power , sexual and cognitive functions , prostate-specific antigen ( PSA ) , plasma lipids , hemoglobin , and insulin-like growth factor I ( IGF-I ) levels , 61 eugonadal men , 18 - 35 yr , were r and omized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone ( GnRH ) agonist , to suppress endogenous testosterone secretion , and weekly injections of 25 , 50 , 125 , 300 , or 600 mg of testosterone enanthate for 20 wk . Energy and protein intakes were st and ardized . The administration of the GnRH agonist plus grade d doses of testosterone result ed in mean nadir testosterone concentrations of 253 , 306 , 542 , 1,345 , and 2,370 ng/dl at the 25- , 50- , 125- , 300- , and 600-mg doses , respectively . Fat-free mass increased dose dependently in men receiving 125 , 300 , or 600 mg of testosterone weekly ( change + 3.4 , 5.2 , and 7.9 kg , respectively ) . The changes in fat-free mass were highly dependent on testosterone dose ( P = 0.0001 ) and correlated with log testosterone concentrations ( r = 0.73 , P = 0.0001 ) . Changes in leg press strength , leg power , thigh and quadriceps muscle volumes , hemoglobin , and IGF-I were positively correlated with testosterone concentrations , whereas changes in fat mass and plasma high-density lipoprotein ( HDL ) cholesterol were negatively correlated . Sexual function , visual-spatial cognition and mood , and PSA levels did not change significantly at any dose . We conclude that changes in circulating testosterone concentrations , induced by GnRH agonist and testosterone administration , are associated with testosterone dose- and concentration-dependent changes in fat-free mass , muscle size , strength and power , fat mass , hemoglobin , HDL cholesterol , and IGF-I levels , in conformity with a single linear dose-response relationship . However , different and rogen-dependent processes have different testosterone dose-response relationships
Testosterone supplementation did not show consistent benefit for cardiovascular risk , sexual function , mood and behavior , or cognition .
Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo .
Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido .
Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function .
Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality , psychological well-being , or mood .
Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of " low testosterone " ( low-T ) for cardiovascular health , sexual function , muscle weakness or wasting , mood and behavior , and cognition .