title: Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized‐controlled trial Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Testosterone therapy increased muscle mass and lipid oxidation in aging men A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. Effect of testosterone treatment on bone mineral density in men over 65 years of age. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. Adverse events associated with testosterone administration. Effects of Low-Dose Testosterone Undecanoate Treatment on Bone Mineral Density and Bone Turnover Markers in Elderly Male Osteoporosis with Low Serum Testosterone Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). 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 Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Impact of long-term testosterone treatment on plasma levels of free TFPI and TF-induced thrombin generation ex vivo in elderly men with low testosterone levels. 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. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency. The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. DHEA in elderly women and DHEA or testosterone in elderly men. Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Effect of testosterone treatment on bone remodelling markers and mineral density in obese dieting men in a randomized clinical trial Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Effect of Testosterone Replacement on Response to Sildenafil Citrate in Men With Erectile Dysfunction
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 Objective . The aim of the present study was to analyse the effect of testosterone therapy  on bone mineral density in healthy elderly men who had low levels of total testosterone . Design . R and omized , double-blind , placebo-controlled study . Participants . Forty-eight men over 60 years old with decreased testosterone levels ( ≤320 ng/dL ) comprised the study . Twenty-five out of 48 received intramuscular injections of testosterone enanthate every three weeks during 12 months ; the remaining 23 participants formed the control group . All participants had measurements of bone mineral density ( BMD ) in both lumbar spine and hip before and at the end of the study as well as testosterone and 17-β estradiol levels . Results : Testosterone treated group exhibited a significant ( p < 0.05 ) increment ( from 1.198 ± 0.153 to 1.240 ± 0.141 g/cm2 ) in lumbar BMD in parallel with a significant ( p < 0.001 ) increment ( from 301 ± 32 to 471 ± 107 ng/dL ) in testosterone concentrations , whereas no significant change occurred in femoral neck BMD . Conclusions . Testosterone therapy elicited a positive effect only in lumbar BMD in elderly men with diminished testosterone serum levels Aging in men is associated with loss of bone mass , impaired physical function and altered body composition . The objective of this proof‐of‐concept r and omized , double‐blind , placebo‐controlled , parallel‐group , single‐center trial was to determine the relative effects of testosterone ( T ) and estradiol ( E2 ) on bone mineral density , body composition , and physical performance in older men . The primary outcome was lumbar spine bone mineral density ( BMD ) , and secondary outcomes were body composition , muscle strength , gait speed , and sex hormone concentrations . Forty three men ( age range , 65–82 years ; mean age 71 years ) with low total T levels < 350 ng/dL were r and omized to one of three groups : 5 g transdermal testosterone gel ( TT ) ( N = 16 ) , anastrozole ( AI ) 1 mg ( N = 14 ) or placebo daily ( N = 13 ) for 12 months . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Both TT and AI increased serum TT levels ( > 500 ng/dL , p < 0.05 ) compared to baseline ; T values remained stable throughout the duration of the trial . At 12 months , TT improved the primary outcome of lumbar spine BMD ( p < 0.01).Both interventions improved knee strength at 12 months compared to baseline ( p < 0.05 ) while lean body mass significantly increased only in the AI group at 6 and 12 months ( 1.49 ± 0.38 kg , p < 0.01 ; 1.24 ± 0.39 kg , p < 0.05 , respectively ) compared to baseline . Interestingly , TT improved fast gait speed at 3 and 12 months ( p < 0.01 , p < 0.05 , respectively ) . In summary , this proof‐of‐concept study confirms that aromatization of T is required for maintaining BMD in older men with low‐T levels . The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed , an observation that needs to be verified in future studies 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 The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment .  Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( -3.96 % ) and body fat ( -5.65 % ) ; negligible changes were found in the control group . TU significantly improved metabolic control : decrease in blood glucose values and mean glycated hemoglobin ( HbA1c ) ( from 10.4 to 8.6 % ) . TU treatment significantly improved symptoms of and rogen deficiency ( including erectile dysfunction ) , with virtually no change in the control group . There were no adverse effects on blood pressure or hematological , biochemical and lipid parameters , and no adverse events . Oral TU treatment of type 2 diabetic men with and rogen deficiency  improves glucose homeostasis and body composition ( decrease in visceral obesity ) , and improves symptoms of and rogen deficiency ( including erectile dysfunction ) . In these men , the benefit of testosterone supplementation therapy exceeds the correction of symptoms of and rogen deficiency and also includes glucose homeostasis and metabolic control BACKGROUND Testosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia . This study was design ed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men . METHODS A subgroup of 30 intermediate-frail and frail elderly men ( 65 - 89 years ) with low to borderline-low testosterone levels were enrolled from a single-center r and omized , double-blind placebo-controlled trial . Participants received either a transdermal testosterone ( 50 mg ) or placebo gel daily for 6 months . Architecture ( muscle thickness , fascicle length , and pennation angle ) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment .  RESULTS Serum testosterone  increased from 11.6 ± 3.5 to 18.0 ± 8.1 nmol/L by 10 days after r and omization in the active group ( but not the placebo group ) and was maintained throughout the treatment period . Testosterone treatment result ed in a preservation of muscle thickness at 6 months while it decreased in the placebo group ( effect size 1.4 [ 95 % confidence interval = 0.3 - 2.5 ; p = .015 ] ) . There was no significant effect of treatment on fascicle length ( effect size 1.9 mm [ 95 % confidence interval = -1.2 to 5.0 mm ; p = .22 ] ) or pennation angle ( effect size 1.2 ° [ 95 % confidence interval = -1.3 to 3.7 ° ; p = .32 ] ) . CONCLUSIONS Testosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness . The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer .  Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) < 70 ng/dL and fatigue score > 3/10 on the Edmonton Symptom Assessment Scale were eligible .  Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone  ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p < .002 ) at 12 months in the testosterone group , whereas no change occurred in the control group . Although there was no change in estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p < .017 ) . The testosterone group had a 0.3 % gain in femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia The indication for testosterone therapy in aging hypogonadal men without hypothalamic , pituitary , or testicular disease remains to be eluci date d. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity , substrate metabolism , body composition , and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone . A r and omized , double-blinded , placebo-controlled study of testosterone treatment ( gel ) was done on 38 men , aged 60–78 years , with bioavailable testosterone < 7.3 nmol/l and a waist circumference > 94 cm .  Insulin-stimulated glucose disposal ( Rd ) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry . Lean body mass ( LBM ) and total fat mass ( TFM ) were measured by dual x-ray absorptiometry , and serum total testosterone was measured by t and em mass spectrometry . Bioavailable testosterone was calculated . Coefficients ( b ) represent the placebo-controlled mean effect of intervention . LBM ( b = 1.9 kg , p = 0.003 ) increased while HDL – cholesterol ( b = −0.12 mmol/l , p = 0.043 ) and TFM decreased ( b = −1.2 kg , p = 0.038 ) in the testosterone group compared to placebo . Basal lipid oxidation ( b = 5.65 mg/min/m2 , p = 0.045 ) increased and basal glucose oxidation ( b = −9.71 mg/min/m2 , p = 0.046 ) decreased in response to testosterone therapy even when corrected for changes in LBM . No significant changes in insulin-stimulated Rd was observed ( b = −0.01mg/min/m2 , p = 0.92 ) . Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels ; however , our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels . Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors . Tau protein deposition is also affected by and rogen supplementation in animals . We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition , in particular the visual-spatial domain . Thirty-six male patients with a new diagnosis of Alzheimer 's disease had their total and bioavailable testosterone levels measured . None of the patients had been on acetylcholinesterase inhibitors .  Ten of the 36 patients ( 28 % ) were deemed biochemically hypogonadal ( total testosterone < 240 ng/dl or 7 nmol/l ) . Five of the hypogonadal patients were r and omized to testosterone and five to placebo . Initial Alzheimer 's Disease Assessment Scale cognitive subscale ( ADAScog ) and Mini Mental Status Examination ( MMSE ) ranged from 31 to 19 and from 17 to 22 , respectively . The  clock drawing test ( CDT ) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities . Normal prostate-specific antigen ( PSA ) levels were essential before treatment with intramuscular testosterone , 200 mg every 2 weeks . Measurement of testosterone , complete blood count , lipids , PSA and neuropsychological cognitive tests were repeated at 3 , 6 , 9 and 12 months of treatment . In the testosterone-treated group , levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l ( p = 0.11 ) . Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l ( p = 0.10 ) . PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml ( p = 0.07 ) . ADAScog improved from a mean of 25 to 16.3 ( p = 0.02 ) ; MMSE improved from a mean of 19.4 to 23.2 ( p = 0.02 ) , CDT also improved from 2.2 to 3.2 ( p = 0.07 ) . One patient stopped treatment because of hypersexual behavior . The placebo-treated group deteriorated gradually . This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition , including visual-spatial skills in mild to moderate Alzheimer 's disease 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 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 Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels BACKGROUND Sex hormones are known to affect cholesterol levels and vascular tone in women . The effects of testosterone on cholesterol and vascular tone in men are less well understood . Low testosterone levels have been associated with higher cholesterol levels in epidemiologic studies , but testosterone replacement has result ed in variable changes in cholesterol levels . Similarly , clinical studies suggest that testosterone may be vasodilatory , but few studies have directly evaluated the effects of testosterone on vascular tone . 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  ( 2 - 2.5 mg patches/d ) or placebo patches for 1 year . Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . RESULTS While total cholesterol , triglyceride , and low-density lipoprotein cholesterol levels did not significantly change during the year of therapy , high-density lipoprotein ( HDL ) levels ( p = .004 ) and , specifically , HDL(2 ) subfraction ( p = .02 ) decreased in men receiving testosterone supplementation . Vascular tone was measured by brachial artery reactivity in 36 men . Endothelium-dependent brachial artery reactivity did not change from baseline measurements in men receiving transdermal testosterone  ( 0.3 + /- 6.7 % to 1.6 + /- 4.6 % ; p = .58 ) or in the placebo group ( 3.2 + /- 5.5 % to 0.7 + /- 5.5 % ; p = .23 ) . CONCLUSIONS Transdermal testosterone decreased HDL(2 ) cholesterol but did not affect vascular reactivity in men older than 65 years selected for low testosterone levels . No study to date has addressed the direct relationship between testosterone replacement and cardiovascular events 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 IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown . A recent r and omized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety . OBJECTIVES To assess the association between testosterone therapy and all-cause mortality , myocardial infa rct ion ( MI ) , or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease . DESIGN , SETTING , AND PATIENTS A retrospective national cohort study of men with low testosterone levels ( < 300 ng/dL ) who underwent coronary angiography in the Veterans Affairs ( VA ) system between 2005 and 2011 . MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality , MI , and ischemic stroke . RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL , 1223 patients started testosterone therapy after a median of 531 days following coronary angiography . Of the 1710 outcome events , 748 men died , 443 had MIs , and 519 had strokes . Of 7486 patients not receiving testosterone therapy  , 681 died , 420 had MIs , and 486 had strokes . Among 1223 patients receiving testosterone therapy , 67 died , 23 had MIs , and 33 had strokes . At 3 years after coronary angiography , the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group , with an absolute risk difference of 5.8%(95%CI , -1.4%to 13.1 % ) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1 % vs 11.3 % ; at 2 years , 15.4 % vs 18.5 % ; and at 3 years , 19.9 % vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease ( test for interaction , P = .41 ) . CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level , the use of testosterone therapy was associated with increased risk of adverse outcomes . These findings may inform the discussion about the potential risks of testosterone therapy BACKGROUND Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men . The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied . METHODS Community-dwelling men , 65 years of age or older , with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter ( 3.5 to 12.1 nmol per liter ) or a free serum testosterone level of less than 50 pg per milliliter ( 173 pmol per liter ) were r and omly assigned to receive placebo gel or testosterone gel , to be applied daily for 6 months . Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification . The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group . RESULTS A total of 209 men ( mean age , 74 years ) were enrolled at the time the trial was terminated . At baseline , there was a high prevalence of hypertension , diabetes , hyperlipidemia , and obesity among the participants . During the course of the study , the testosterone group had higher rates of cardiac , respiratory , and dermatologic events than did the placebo group . A total of 23 subjects in the testosterone group , as compared with 5 in the placebo group , had cardiovascular-related adverse events . The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period . As compared with the placebo group , the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load . CONCLUSIONS In this population of older men with limitations in mobility and a high prevalence of chronic disease , the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events . The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy . ( Clinical Trials.gov number , NCT00240981 . This prospect i ve 2-year , single-center , r and omized , placebo-controlled , open-label clinical trial was performed to evaluate the efficacy of low-dose testosterone undecanoate ( TU ) treatment on bone mineral density ( BMD ) and biochemical markers of bone turnover in elderly male osteoporosis with low serum testosterone . A total of 186 elderly male osteoporosis patients with low serum testosterone were r and omized into three groups : low-dose TU ( 20 mg , per day ) , st and ard-dose TU ( 40 mg , per day ) , and placebo group with a 24-month followup . Since the 6th month in st and ard-dose TU group or since the 12th month followup in low-dose TU group and throughout the study , lumbar spine and femoral neck BMD and serum levels of free testosterone , estradiol , and bone alkaline phosphatase significantly increased . There were no significant differences between groups of low-dose TU and st and ard dose TU in the percentage of changes of these data since the 18th month followup and throughout the study . No side effects on prostate gl and s including prostate specific antigen were found . In conclusion , low-dose TU ( 20 mg , per day ) may be a cost effective and safe protocol for treating elderly male osteoporosis with low serum testosterone 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 OBJECTIVES To To compare testosterone undecanoate versus propionyl-L-carnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms . METHODS A total of 120 patients were r and omized into three groups . The mean patient age was 66 years ( range 60 to 74 ) . Group 1 was given testosterone undecanoate 160 mg/day , the second group was given propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day . The third group was given a placebo ( starch ) . Drugs and placebo were given for 6 months . The assessed variables were total prostate-specific antigen , prostate volume , peak systolic velocity , end-diastolic velocity , resistive index of cavernosal penile arteries , nocturnal penile tumescence , total and free testosterone , prolactin , luteinizing hormone , International Index of Erectile Function score , Depression Melancholia Scale score , fatigue scale score , and incidence of side effects . The assessment was performed at intervals before , during , and after therapy . RESULTS Testosterone and carnitines significantly improved the peak systolic velocity , end-diastolic velocity , resistive index , nocturnal penile tumescence , International Index of Erectile Function score , Depression Melancholia Scale score , and fatigue scale score . Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score . Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone ; carnitines did not . No drug significantly modified prostate-specific antigen or prolactin . Carnitines and testosterone proved effective for as long as they were administered , with suspension provoking a reversal to baseline values . Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension . Placebo administration proved ineffective . Negligible side effects emerged . CONCLUSIONS Testosterone and , especially , carnitines proved to be active drugs for the therapy of symptoms associated with male aging objectives We have recently shown that , in men with erectile dysfunction ( ED ) , free testosterone ( FT ) directly correlates with penile arterial inflow . This led us to further investigate the effect(s ) of and rogen administration on cavernous arteries in patients failing sildenafil treatment The stimulatory effects of testosterone on erythropoiesis are very well known , but the mechanisms underlying the erythropoietic action of testosterone are still poorly understood , although erythropoietin has long been considered a potential mediator . A total of 108 healthy men > 65 years old with serum testosterone concentration < 475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University , and r and omized to receive a 60‐cm2 testosterone or placebo patch for 36 months . Ninety‐six subjects completed the trial . We used information and stored serum specimens from this trial to test the hypothesis that increasing testosterone increases haemoglobin by stimulating erythropoietin production . We used information of 67 men , 43 in the testosterone group and 24 in the placebo group who had banked specimens available for assays of testosterone , haemoglobin and erythropoietin at baseline and after 36 months . The original r and omized clinical study was primarily design ed to verify the effects of testosterone on bone mineral density . The primary outcome of this report was to investigate whether or not transdermal testosterone increases haemoglobin by increasing erythropoietin levels . The mean age ± SD of the 67 subjects at baseline was 71.8 ± 4.9 years . Testosterone replacement therapy for 36 months , as compared with placebo , induced a significant increase in haemoglobin ( 0.86 ± 0.31 g/dL , p = 0.01 ) , but no change in erythropoietin levels ( −0.24 ± 2.16 mIU/mL , p = 0.91 ) . Included time‐varying measure of erythropoietin did not significantly account for the effect of testosterone on haemoglobin ( Treatment‐by‐time : β = 0.93 , SE = 0.33 , p = 0.01 ) . No serious adverse effect  was observed . Transdermal testosterone treatment of older men for 36 months significantly increased haemoglobin , but not erythropoietin levels . The haematopoietic effect of testosterone does not appear to be mediated by stimulation of erythropoietin production OBJECTIVE Hypogonadism and subthreshold depression are common conditions in elderly men . The objective of this study was to examine the effect of testosterone treatment in older , hypogonadal men with subthreshold depression . METHOD A r and omized , double-blind , placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older ( N = 33 ) with screening total testosterone levels of < or= 280 ng/dL and subthreshold depression ( dysthymia or minor depression , according to DSM-IV ) . Recruitment for the study was conducted from November 2002 through May 2005 . Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks , followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel . The primary outcome measure was the change in the Hamilton Rating Scale for Depression ( HAM-D ) score from baseline to the end of the double-blind phase . Secondary outcome measures were remission of subthreshold depression ( defined a priori as a HAM-D score < or= 7 ) and changes in the Hopkins Symptom Checklist depression scale , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the short-form 16-item Quality of Life Enjoyment and Satisfaction Question naire . RESULTS At the end of the double-blind phase , testosterone-treated men had a greater reduction in HAM-D scores ( p = .024 ) and a higher remission rate of subthreshold depression ( 52.9 % vs. 18.8 % , p = .041 ) than did placebo-treated men , but there were no differences in other secondary outcome measures between groups . At the end of the open-label phase , the testosterone group had sustained improvement , the control group improved , and there were no differences between groups in any outcome measures . CONCLUSION These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism . Larger studies are needed to corroborate these findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00202462 Growth hormone is the major regulator of growth and body composition . Pulsatile GH secretion declines exponentially with age . Testosterone replacement is being increasingly offered to older men with age-related low testosterone .  Testosterone administration has been shown to stimulate GH secretion . However , little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men . OBJECTIVE This r and omized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone . DESIGN Thirty-seven men , ≥65years with total testosterone < 350ng/dL were r and omized to 5 g transdermal testosterone gel ( TT ) , 1 mg oral aromatase inhibitor ( AI ) or placebo daily for 12months . Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months . Secondary outcomes included IGF-1 evaluated at baseline , 3 and 6months . RESULTS At 3months , mean GH and in IGF-1 were similar between the three groups . At 6months , IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo ( P=0.03 ) . Both intervention groups significantly increased GH pulse frequency ( TT-group , P=0.04 ; AI-group , P=0.05 ) compared to placebo . The GH secretory-burst mode ( duration ) significantly decreased in the TT-group ( P=0.0018 ) compared to placebo while it remained unchanged in the AI-group ( P=0.059 ) . CONCLUSIONS In older men  , testosterone  increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels INTRODUCTION Addition of testosterone ( T ) may improve the action of phosphodiesterase type 5 inhibitors ( PDE5-Is ) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels . AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is  and to specify the baseline T levels at which such an effect becomes significant . METHODS A multicenter , multinational , double-blind , placebo-controlled study of 173 men , 45 - 80 years , nonresponders to treatment with different PDE5-Is , with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day ( OAD ) for 4 weeks ; if not successful , they were r and omized in a double-blind , placebo-controlled design to receive placebo or a 1 % hydroalcoholic T gel ( 50 mg/5 g gel ) , to be increased to 10 mg T if results were clinical ly unsatisfactory . Main Outcomes Measures . Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses ( Sexual Encounter Profile 3 question ) . RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups . In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL , no additional effect of T administration to men optimally treated with PDE5-Is was encountered . The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks . Furthermore , addition of T to this PDE5-I regimen is beneficial , but only in hypogonadal men with baseline T levels ≤ 3 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 We used longitudinal data from the Massachusetts Male Aging Study , a large population -based r and om- sample cohort of men aged 40 - 70 yr at baseline , to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends . Of 1,709 men enrolled in 1987 - 1989 , 1,156 were followed up 7 - 10 yr afterward . By repeated- measures statistical analysis , we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data , the cross-sectional trend between subjects within the follow-up data , and the longitudinal trend within subjects between baseline and follow-up . Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data , whereas both free and albumin-bound T declined at about 2%/yr , all significantly more steeply than within the baseline data . Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data , similarly to baseline . The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T ( 1.6%/yr ) and bioavailable T ( 2 - 3%/yr ) . Dehydroepi and rosterone , dehydroepi and rosterone sulfate , cortisol , and estrone showed significant longitudinal declines , whereas dihydrotestosterone , pituitary gonadotropins , and PRL rose longitudinally . Apparent good health , defined as absence of chronic illness , prescription medication , obesity , or excessive drinking , added 10 - 15 % to the level of several and rogens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends . The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in and rogen levels Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone < 10 nmol/L or free and rogen index < 30 % ) . Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD The cardiovascular effects of testosterone treatment are debated . Osteoprotegerin ( OPG ) is an independent marker of cardiovascular risk . We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels . A r and omized , double-blinded , placebo-controlled study of 6 months testosterone therapy ( gel )  in 38 men aged 60 - 78 years with bioavailable testosterone < 7.3 nmol/l and waist circumference > 94 cm was performed .  Clinical evaluation , OPG , and C-reactive protein ( CRP ) measurements were carried out . Lean body mass ( LBM ) , total fat mass , and bone mineral density ( BMD ) were established by dual X-ray absorptiometry . Visceral adipose tissue ( VAT ) and subcutaneous adipose tissue ( SAT ) were measured by magnetic resonance imaging . Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM ( Δ LBM positive ) , n=14 . Data are presented as median ( interquartile range ) . Testosterone therapy  decreased total fat mass and SAT , whereas VAT was unchanged ( n=38 ) . OPG levels decreased during testosterone therapy ( from 2.0 ( 1.9 - 2.5 ) to 1.9 ( 1.6 - 2.2 ) ng/ml , p<0.05 vs. placebo ) , whereas CRP levels were unchanged ( n=38 ) . In responders to testosterone therapy ( n=14 ) , ΔOPG levels were inversely associated with ΔSAT ( r= - 0.60 , p=0.03 ) and positively associated with ΔVAT ( r=0.56 , p=0.04 ) . OPG levels  decreased during testosterone therapy suggesting decreased cardiovascular risk . Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution 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 Muscle wasting in older men may be related to and rogen deficiency . We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older ( age > 60 years ) men with blood testosterone levels < 14 nmol/L. Subjects ( n = 7 per group ) received testosterone enanthate 200 mg i.m . or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks . A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group . Total body mass , haemoglobin and packed cell volume also increased significantly ( p < 0.05 ) . No improvements in h and grip strength , isometric strength of knee flexors and extensors or leg extensor power were seen in either group . Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function Men have a higher incidence of cardiovascular disease ( CVD ) than women of similar age , and it has been suggested that testosterone may influence the development of CVD . Recently , we demonstrated that elderly men with low testosterone levels had lower plasma levels of free tissue factor pathway inhibitor ( TFPI ) Ag associated with shortened tissue factor (TF)-induced coagulation initiation in a population based case-control study . Our hypothesis was that one year of testosterone treatment to physiological levels in elderly men would increase the levels of free TFPI Ag in plasma and have a favorable effect on TF-induced coagulation .  Twenty-six men with low testosterone levels ( < or = 11.0 nM ) were r and omly assigned to treatment with intramuscular testosterone depot injections ( testosterone undecanoate 1,000 mg ) or placebo in a double-blinded study . Each participant received a total of five injections , at baseline , 6 , 16 , 28 and 40 weeks , and TF-induced thrombin generation ex vivo and plasma free TFPI Ag were measured after one year . At the end of the study total and free testosterone levels were significantly higher in the testosterone treated group ( 14.9 + /- 4.5 nM vs. 8.1 + /- 2.4 nM ; p < 0.001 , and 363.3 + /- 106.6 pM vs. 187.3 + /- 63.2 pM ; p < 0.001 , respectively ) . Testosterone treatment for one year did neither cause significant changes in TF-induced thrombin generation ex vivo nor changes in plasma levels of free TFPI Ag . In conclusion , normalising testosterone levels by testosterone treatment for 12 months in elderly men did not affect TF-induced coagulation or plasma TFPI levels . The potential antithrombotic role of testosterone therapy remains to be eluci date 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 IMPORTANCE Testosterone use in older men is increasing , but its long-term effects on progression of atherosclerosis are unknown . OBJECTIVE To determine the effect of testosterone administration on sub clinical atherosclerosis progression in older men with low or low-normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Testosterone 's Effects on Atherosclerosis Progression in Aging Men ( TEAAM ) was a placebo-controlled , double-blind , parallel-group r and omized trial involving 308 men 60 years or older with low or low-normal testosterone levels ( 100 - 400 ng/dL ; free testosterone < 50 pg/mL ) , recruited at 3 US centers . Recruitment took place between September 2004 and February 2009 ; the last participant completed the study in May 2012 . INTERVENTIONS One hundred fifty-six participants were r and omized to receive 7.5 g of 1 % testosterone and 152 were r and omized  to receive placebo gel packets daily for 3 years . The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES Co primary outcomes included common carotid artery intima-media thickness and coronary artery calcium ; secondary outcomes included sexual function and health-related quality of life . RESULTS Baseline characteristics were similar between groups : patients were a mean age of 67.6 years ; 42 % had hypertension ; 15 % , diabetes ; 15 % , cardiovascular disease ; and 27 % , obesity . The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group ( mean difference adjusted for age and trial site , 0.0002 mm/year ; 95 % CI , -0.003 to 0.003 , P = .89 ) . The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group ( adjusted mean difference , -10.8 Agatston units/year ; 95 % CI , -45.7 to 24.2 ; P = .54 ) . Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone . Sexual desire , erectile function , overall sexual function scores , partner intimacy , and health-related quality of life did not differ significantly between groups . Hematocrit and prostate-specific antigen levels increased more in testosterone group . CONCLUSIONS AND RELEVANCE Among older men with low or low-normal testosterone levels , testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life . Because this trial was only powered to evaluate atherosclerosis progression , these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00287586 Several r and omized trials of and rogen supplementation in older men have been undertaken . However , the relative contributions of testosterone ( T ) and estrogens on bone metabolism in aging men are controversial . Within the setting of two double-blind , placebo-controlled studies , we evaluated the effect of dihydrotestosterone ( DHT ) and recombinant human chorionic gonadotropin ( rhCG ) on bone turnover in healthy , community-dwelling older men with partial and rogen deficiency ( total T < or = 15 nmol/liter ) . In the first study , 35 men ( age 68.3 + /- 6.8 yr ; baseline T , 13.9 + /- 3.3 nmol/liter ) were r and omized to receive either daily transdermal DHT ( n = 17 ) or placebo for 3 months . In the second study , 40 men ( age 67.4 + /- 5.4 yr ; baseline T , 11.4 + /- 2.2 nmol/liter ) were r and omized to receive either rhCG s.c . ( n = 20 ) , two injections weekly , or placebo for 3 months . The following parameters were measured before , monthly during , and 1 month after treatment : serum T , estradiol ( E2 ) , and LH ; markers of bone formation , serum amino-terminal propeptide of type I procollagen ( S-PINP ) and osteocalcin ; markers of bone resorption , serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline . Compared with placebo , treatment with DHT significantly increased serum DHT and suppressed LH and T levels , whereas E2 concentrations and markers of bone turnover did not change . In contrast , rhCG therapy significantly increased both T and E2 , with the increases in E2 being supraphysiological . At the same time , rhCG significantly increased S-PINP concentrations with peak levels after 1 month ( Delta40 % ; P = 0.02 compared with placebo ) . In contrast , serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change . The change in S-PINP levels correlated with the change in E2 levels ( r = 0.59 ; P = 0.02 ) but not with a change in T. We conclude that in older men with partial age-related and rogen deficiency , rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption . In contrast , treatment with a pure , nonaromatizable and rogen ( DHT ) has no effect on bone turnover despite a 20-fold increase in serum levels . Bone resorption was not accelerated during unchanged ( DHT ) or increased ( rhCG ) E2 levels , suggesting that minimal E2 levels are needed to maintain stable resorption , although direct and rogen receptor-mediated effects can not be excluded . If and rogen supplementation is required for aging men , aromatizable and rogens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone And rogen therapy may precipitate  obstructive sleep apnea in men . Despite increasing and rogen use in older men , few studies have examined sleep and breathing . R and omized , double-blind , placebo-controlled studies examining effects of testosterone simultaneously on sleep , breathing , and function in older men are not available . Seventeen community-dwelling healthy men over the age of 60 yr were r and omized to receive three injections of i m testosterone esters at weekly intervals ( 500 mg , 250 mg , and 250 mg ) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout .  Polysomnography , anthropometry , and physical , mental , and metabolic function were assessed at baseline and after each treatment period . Testosterone treatment reduced total time slept ( approximately 1 h ) , increased the duration of hypoxemia ( approximately 5 min/night ) , and disrupted breathing during sleep ( total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour ) ( all P < 0.05 ) . Despite expected effects on body composition ( increase in total and lean mass , reduction in fat mass , P < 0.05 , bioimpedance method ) , upper airway dimensions did not change ( acoustic reflectometry ) . Driving ability ( computer simulation ) , physical activity ( accelerometry , Physical Activity Scale in the Elderly ) , quality of life ( SF36 , Functional Outcomes of Sleep Question naire ) , mood ( Profile of Mood States Question naire ) , sleepiness ( Epworth , Stanford scales ) , and insulin resistance ( homeostasis model ) also were not changed by treatment . Short-term administration of high-dose testosterone  shortens sleep and worsens sleep apnea in older men but did not alter physical , mental , or metabolic function . These changes did not appear to be due to upper airway narrowing . Further study of longer-term lower-dose and rogen therapy on sleep and breathing is needed to evaluate its safety in older men OBJECTIVE The objective of the study was to assess the effect of T treatment on constitutional and sexual symptoms in men with type 2 diabetes ( T2D ) . DESIGN This was a r and omized double-blind , parallel , placebo-controlled trial . SETTING The study was conducted at a tertiary referral center . PATIENTS Men aged 35 - 70 years with T2D , a hemoglobin A1c less than 8.5 % , and a total T level less than 12.0 nmol/L ( 346 ng/dL ) with mild to moderate aging male symptoms and erectile dysfunction . INTERVENTION Eighty-eight participants were r and omly assigned to 40 weeks of i m T undecanoate ( n = 45 ) or matching placebo ( n = 43 ) . MAIN OUTCOME MEASURES Constitutional symptoms using the aging male symptoms ( AMS ) score , sexual desire ( question 17 AMS score ) , and erectile function ( International Index of Erectile Function-5 ) . RESULTS T treatment did not substantially improve aging male symptoms [ mean adjusted difference ( MAD ) in change over 40 weeks across the T and placebo groups in AMS total score , -0.9 ( 95 % confidence interval [ CI ] -4.1 , 2.2 ) , P = .67 ] or sexual desire [ MAD in question 17 AMS , -0.3 ( 95 % CI -0.8 , 0.2 ) , P = .17 ] . Although compared with placebo , erectile function in men assigned to T was reduced [ MAD in International Index of Erectile Function abridged version 5 , -2.0 ( 95 % CI -3.4 , -0.6 ) , P < .02 ] , there was no significant difference between baseline and 40-week International Index of Erectile Function abridged version 5 scores if both groups were analyzed separately . At baseline , symptoms were worse in men with depression and microvascular complications but did not correlate with T levels . CONCLUSIONS In this trial , T treatment did not substantially improve constitutional or sexual symptoms in obese , aging men with T2D with mild to moderate symptoms and modest reduction in T levels typical for the vast majority of such men 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 ] . ) 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 To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men , 100 obese men aged 53 years ( interquartile range 47–60 ) with a total testosterone level < 12 nmol/L receiving 10 weeks of a very low energy diet ( VLED ) followed by 46 weeks of weight maintenance were r and omly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate ( n = 49 , cases ) or matching placebo ( n = 51 , controls ) . Pre-specified outcomes were between-group differences ( mean adjusted difference , MAD ) in serum c-telopeptide ( CTx ) , N-terminal propeptide of type 1 procollagen ( P1NP ) and bone mineral density ( BMD ) . At trial end , CTx was significantly reduced in men receiving testosterone compared to placebo , MAD −66 ng/L ( 95 % CI −113 , −18 ) , p = 0.018 , and this was apparent already after the 10 week VLED phase , MAD −63 ng/L ( 95 % CI −108 , −18 ) , p = 0.018 . P1NP was marginally increased after VLED , MAD + 4.2 ug/L ( 95 % CI −0.01 , + 8.4 ) , p = 0.05 but lower at study end , MAD −5.6 ug/L ( 95 % CI −10.1 , −1.1 ) , p = 0.03 . No significant changes in sclerostin , lumbar spine BMD or femoral BMD were seen . We conclude that in obese men with low testosterone levels  undergoing weight loss , bone remodelling markers are modulated in a way that may have favourable effects on bone mass OBJECTIVES To investigate the effects of testosterone supplementation on bone , body composition , muscle , physical function , and safety in older men . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING A major medical institution . PARTICIPANTS One hundred thirty-one men ( mean age 77.1 + /- 7.6 ) with low testosterone , history of fracture , or bone mineral density ( BMD ) T-score less than -2.0 and frailty . INTERVENTION Participants received 5 mg/d of testosterone or placebo for 12 to 24 months ; all received calcium ( 1500 mg/d diet and supplement ) and cholecalciferol ( 1,000 IU/d ) . MEASUREMENTS BMD of hip , lumbar spine , and mid-radius ; body composition ; sex hormones , calcium-regulating hormones ; bone turnover markers ; strength ; physical performance ; and safety parameters . RESULTS Ninety-nine men ( 75.6 % ) completed 12 months , and 62 ( 47.3 % ) completed end therapy ( mean 23 months ; range 16 - 24 months for 62 who completed therapy ) . Study adherence was 54 % , with 40 % of subjects maintaining 70 % or greater adherence . Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL , respectively , in the treatment group . BMD on testosterone  increased 1.4 % at the femoral neck and 3.2 % at the lumbar spine ( P=.005 ) and decreased 1.3 % at the mid-radius ( P<.001 ) . There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance . There were no differences in safety parameters . CONCLUSION Older , frail men receiving  testosterone replacement increased testosterone levels and had favorable changes in body composition , modest changes in axial BMD , and no substantial changes in physical function OBJECTIVE To investigate the effects of oral testosterone undecanoate ( TU ) on symptoms associated with late-onset hypogonadism ( LOH ) . Design Multicenter , r and omized , double-blind , placebo-controlled . METHODS The study was performed in 14 study centers in seven European countries . Men > or = 50 years ( n=322 ) with symptoms of hypogonadism and testosterone deficiency ( calculated free testosterone < 0.26 nmol/l ) were r and omized and treated for 12 months with placebo or oral TU 80 , 160 or 240 mg/day . Primary outcome was the total score on the Aging Males ' Symptoms ( AMS ) rating scale after six months of treatment . RESULTS Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU result ed in an improved total AMS score at month 6 , but differences between groups were not statistically significant . There was greater improvement in subjects < 60 years when compared with subjects > or = 60 years ( P=0.001 ) , but baseline testosterone level had no influence on treatment response . The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 ( P=0.008 ) and 12 ( P=0.012 ) compared with placebo , but not with 80 and 240 mg/day . Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates . CONCLUSIONS In one of the largest placebo-controlled studies of testosterone therapy in LOH , oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo , except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day BACKGROUND Erectile dysfunction and low testosterone levels frequently occur together . OBJECTIVE To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels . DESIGN R and omized , double-blind , parallel , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00512707 ) SETTING Outpatient academic research center . PARTICIPANTS Men aged 40 to 70 years with scores of 25 or less for the erectile function domain ( EFD ) of the International Index of Erectile Function , total testosterone levels less than 11.45 nmol/L ( < 330 ng/dL ) , or free testosterone levels less than 173.35 pmol/L ( < 50 pg/mL ) . INTERVENTION Sildenafil dose was optimized , and 140 participants were then r and omly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants . All participants were included in the primary analysis , although 10 in the testosterone group and 12 in the placebo group did not complete the study . RESULTS At baseline , the 2 groups had similar EFD scores . Administration of sildenafil alone was associated with a substantial increase in EFD score ( mean , 7.7 [ 95 % CI , 6.5 to 8.8 ] ) , but change in EFD score after r and omization did not differ between the groups ( difference , 2.2 [ CI , -0.8 to 5.1 ] ; P = 0.150 ) . The findings were similar for other domains of sexual function in younger men , more obese men , and men with lower baseline testosterone levels or an inadequate response to sildenafil alone . Frequency of adverse events was similar for testosterone and placebo groups . LIMITATION Whether testosterone could improve erectile function without sildenafil was not studied . CONCLUSION Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving  erectile function in men with erectile dysfunction and low testosterone levels . PRIMARY FUNDING SOURCE National Institute of Child Health and Human Development
target: The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive .
  However , supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events , all-cause mortality , or prostatic events .
background: Testosterone deficiency ( TD ) may induce a series of clinical symptoms .
  Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients ’ quality of life .
  Given the conflicting findings across studies , this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD .