title: Effects of testosterone supplementation in the aging male. 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 Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial. A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. Effect of testosterone treatment on bone mineral density in men over 65 years of age. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. Differential anabolic effects of testosterone and amino acid feeding in older men. 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 (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Beneficial effects of testosterone undecanoate on the lipoprotein profiles in healthy elderly men. A placebo controlled study. Effects of Androgen Administration in Men with the AIDS Wasting Syndrome Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity. Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. 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. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Effects of testosterone replacement in hypogonadal men. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. 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. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial.
abstract: Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) .  Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have  serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy 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 Nutritional depletion commonly occurs in patients with COPD , causing muscle wasting and impaired physiologic function . Two hundred seventeen patients with COPD participated in a placebo-controlled , r and omized trial investigating the physiologic effects of nutritional intervention alone ( N ) for 8 wk or combined with the anabolic steroid n and rolone decanoate ( N + A ) . N and rolone decanoate or placebo ( P ) was injected intramuscularly ( women , 25 mg ; men , 50 mg ) in a double-blind fashion on Days 1 , 15 , 29 , and 43 . Nutritional intervention consisted of a daily high caloric supplement ( 420 kcal ; 200 ml ) . Also , all patients participated in an exercise program . In the depleted patients , both treatment regimens induced a similar significant body weight gain ( 2.6 kg ) but different body compositional changes . Particularly in the last 4 wk of treatment , weight gain in the N group was predominantly due to an expansion of fat mass ( p < 0.03 versus P and N + A ) , whereas the relative changes in fat-free mass ( FFM ) and other measures of muscle mass were more favorable in the N + A group ( p < 0.03 versus P ) . Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 wk of treatment , but after 8 wk only N + A was significantly different from P ( p < 0.03 ) . Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects We conducted a prospect i ve , r and omized study in chronic hemodialysis patients in order to determine whether the erythropoietic response to low dose recombinant human erythropoietin ( rHuEpo ) could be enhanced by administration with and rogens . Patients received rHuEpo 40 U/kg intravenously three times weekly either alone  ( Group 1 , n = 6 ) or with weekly intramuscular injection of 2 mg/kg n and rolone decanoate  ( Group 2 , n = 6 ) for up to 16 weeks . Baseline hct , ferritin , N-terminal parathyroid hormone , and aluminum levels were similar . The mean weekly rate of rise in hct was 0.32 + /- 0.13 % in Group 1 and 0.37 + /- 0.11 % in Group 2 , p = NS . Three of 6 patients in Group 1 , but only 1 of 6 patients in Group 2 , reached the target hct of 30 % within 16 weeks . Two patients in Group 2 requested that the n and rolone decanoate be stopped prior to reaching target hct because of unacceptable side effects ( acne ) . We conclude that many chronic hemodialysis patients appear to respond adequately to rHuEpo at the dose used in our study . N and rolone decanoate does not enhance the response rate to this rHuEpo dose and is associated with significant side effects 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 Long-term glucocorticoid therapy  in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone . We tested the effect of two and rogens , testosterone and its minimally aromatizable analog n and rolone , on muscle mass ( dual x-ray absorptiometry ) , muscle strength ( knee flexion and extension by isokinetic dynamometry ) , bone mineral density ( BMD ) , and quality of life ( Qualeffo-41 question naire ) in 51 men on a mean daily prednisone dose of 12.6 + /- 2.2 mg . Men were r and omized , double blind , to testosterone ( 200 mg mixed esters ) , n and rolone decanoate ( 200 mg ) , or placebo given every fortnight by i m injection for 12 months . At 12 months , both and rogens increased muscle mass ( mean change from baseline + 3.5 % , + 5.8 % , and -0.9 % in testosterone , n and rolone , and placebo groups , respectively , P < 0.0001 ) and muscle strength ( P < 0.05 ) . Lumbar spine BMD increased significantly only in men treated with testosterone ( 4.7 + /- 1.1 % , P < 0.01 ) . There was no significant change in hip or total body BMD . Testosterone , but not n and rolone or placebo , improved overall quality of life ( P < 0.001 ) . These results suggest that and rogen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for and rogen action on bone but not on muscle Although weight loss associated with human immunodeficiency virus ( HIV ) infection is multifactorial in its pathogenesis , it has been speculated that hypogonadism , a common occurrence in HIV disease , contributes to depletion of lean tissue and muscle dysfunction . We , therefore , examined the effects of testosterone replacement by means of And roderm , a permeation-enhanced , nongenital transdermal system , on lean body mass , body weight , muscle strength , health-related quality of life , and HIV-disease markers . We r and omly assigned 41 HIV-infected , ambulatory men , 18 - 60 yr of age , with serum testosterone levels below 400 ng/dL , to 1 of 2 treatment groups : group I , two placebo patches ( n = 21 ) ; or group II , two testosterone patches design ed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment . Serum total and free testosterone and dihydrotestosterone levels increased , and LH and FSH levels decreased in the testosterone-treated , but not in the placebo-treated , men . Lean body mass and fat-free mass , measured by dual energy x-ray absorptiometry , increased significantly in men receiving testosterone patches [ change in lean body mass , + 1.345 + /- 0.533 kg ( P = 0.02 compared to no change ) ; change in fat-free mass , + 1.364 + /- 0.525 kg ( P = 0.02 compared to no change ) ] , but did not change in the placebo group [ change in lean body mass , 0.189 + /- 0.470 kg ( P = NS compared to no change ) ; change in fat-free mass , 0.186 + /- 0.470 kg ( P = NS compared to no change ) ] . However , there was no significant difference between the 2 treatment groups in the change in lean body mass . The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels ( r = 0.41 ; P = 0.02 ) . The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches ( P = 0.04 ) . There was no significant change in body weight in either treatment group . Changes in overall quality of life scores did not correlate with testosterone treatment ; however , in the subcategory of role limitation due to emotional problems , the men in the testosterone group improved an average of 43 points of a 0 - 100 possible score , whereas those in the placebo group did not change . Red cell count increased in the testosterone group ( change in red cell count , + 0.1 + /- 0.1 10(12)/L ) but decreased in the placebo group ( change in red cell count , -0.2 + /- 0.1 10(12)/L ) . CD4 + and CD8 + T cell counts and plasma HIV copy number did not significantly change during treatment . Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group . Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass , a significantly greater reduction in fat mass than that achieved with placebo treatment , an increased red cell count , and an improvement in role limitation due to emotional problems . Further studies are needed to assess whether testosterone supplementation can produce clinical ly meaningful changes in muscle function and disease outcome in HIV-infected men 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 BACKGROUND Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men . The impact of the decreased and rogen levels on cognition and health perception has received little attention . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - 87 ) with bioavailable testosterone levels below 128 ng/dl ( 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 . 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 ] , cognitive tests ( Digit Symbol , Digit Span , Trailmaking A and B ) , health perception ( Medical Outcome Survey Short-form 36 or SF-36 ) , lower extremity muscle strength and power , and calcium intake . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial .  Bioavailable testosterone levels increased from 93 + /- 34 ( SD ) to 162 + /- 100 ng/dl ( p < .002 ) at 12 months in the testosterone group ( n = 24 ) while no change occurred in the control group ( n = 20 ) . While there was no change in estradiol levels in either group , estrone levels increased in the testosterone group ( 28 + /- 7 to 32 + /- 9 pg/dl , p = .017 ) . Scores on the Digit Symbol test improved in both the testosterone and placebo groups . Scores on Trailmaking B improved in men treated with testosterone ( p < .005 ) , although the changes were not statistically different from the changes seen in the placebo group . Twelve-month scores on Trailmaking B for the entire group were correlated with 12-month testosterone levels ( p = .016 ) . Scores for health perception measured by SF-36 did not change significantly , though scores of mental and general health declined in both groups during the 12-month intervention . Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role ( p = .022 ) , vitality ( p = .036 ) , and the physical composite score ( p = .010 ) . CONCLUSIONS Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function . Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups The interaction between testosterone and exogenous amino acids was studied in older men before and after 6 months of testosterone administration . Twelve healthy older male subjects were r and omly assigned in double-blind fashion to receive either testosterone enanthate [ T ; n = 7 ; 68 + /- 3 ( + /-SE ) yr ] or placebo ( n = 5 ; 67 + /- 3 yr ) for 6 months . Muscle protein kinetics were determined using stable isotope methodology , arterial-venous difference across leg muscle , and muscle biopsies . In addition , ubiquitin-proteasome activity was measured in muscle biopsies as an indicator of muscle protein breakdown . T improved fasting net protein balance , although it remained significantly negative . The improvement in net balance was due to a decrease in muscle protein breakdown , as protein synthesis was unchanged . Ubiquitin-proteasome activity was also decreased with T. Exogenous amino acids increased protein synthesis in both placebo and T groups , but to a lesser degree after 6 months of T treatment . These results indicate that prolonged T administration increases net protein balance in the fasted state , but no additive effect is demonstrated when combined with amino acid feedings . Taken together , however , these diverse stimulatory effects can increase lean body mass and muscle strength over time 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 ) 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 We investigated the effects of 6 mo of near-physiological testosterone administration  to older men on skeletal muscle function and muscle protein metabolism .  Twelve older men ( > or = 60 yr ) with serum total testosterone concentrations < 17 nmol/l ( 480 ng/dl ) were r and omly assigned in double-blind manner to receive either placebo ( n = 5 ) or testosterone enanthate ( TE ; n = 7 ) injections . Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point . TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l . Lean body mass ( LBM ) , muscle volume , prostate size , and urinary flow were measured at baseline and at 6 mo . Protein expression of and rogen receptor ( AR ) and insulin-like growth factor I , along with muscle strength and muscle protein metabolism , were measured at baseline and at 1 and 6 mo of treatment . Hematological parameters were followed monthly throughout the study . Older men receiving  testosterone increased total and leg LBM , muscle volume , and leg and arm muscle strength after 6 mo . LBM accretion result ed from an increase in muscle protein net balance , due to a decrease in muscle protein breakdown . TE treatment increased expression of AR protein at 1 mo , but expression returned to pre-TE treatment levels by 6 mo . IGF-I protein expression increased at 1 mo and remained increased throughout TE administration . We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease ( COPD ) patients . This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement . Ten severe COPD patients without clinical ly significant oxygen ( O2 ) desaturation during exercise , and seven healthy subjects , performed five exercise tests at 75 % of maximally tolerated work rate . Inspired oxygen fraction ( FI , O2 ) was varied ( 0.21 , 0.3 , 0.5 , 0.75 and 1.0 ) among tests in a r and omized order . Ventilation ( V'E ) was measured , and end-inspiratory ( EILV ) and end-expiratory ( EELV ) lung volume changes were assessed from inspiratory capacity manoeuvres . In the patients , compared to room air , endurance time increased with FI , O2=0.3 ( mean+/-SEM 92+/-20 % ) and increased further with FI , O2=0.5 ( 157+/-30 % ) . At isotime , compared to room air , there were significant reductions in dyspnoea score , EELV , EILV , V'E and respiratory frequency ( fR ) with FI , O2=0.3 . Improved endurance time negatively correlated with change in EELV ( r=0.48 , p=0.002 ) and EILV ( r=0.43 , p=0.005 ) . The dyspnoea rating decrease correlated with fR decrease . In healthy subjects , smaller V'E and fR decreases were observed at FI , O2=0.5 , accompanied by more modestly increased endurance .  Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients , which may be partly related to decreased hyperinflation and slower breathing pattern . This effect is maximized at an inspired oxygen fraction of 0.5 BACKGROUND Athletes often take and rogenic steroids in an attempt to increase their strength . The efficacy of these substances for this purpose is unsubstantiated , however . METHODS We r and omly assigned 43 normal men to one of four groups : placebo with no exercise ; testosterone with no exercise ; placebo plus exercise ; and testosterone plus exercise . The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks . The men in the exercise groups performed st and ardized weight-lifting exercises three times weekly . Before and after the treatment period , fat-free mass was determined by underwater weighing , muscle size was measured by magnetic resonance imaging , and the strength of the arms and legs was assessed by bench-press and squatting exercises , respectively . RESULTS Among the men in the no-exercise groups , those given testosterone had greater increases than those given placebo in muscle size in their arms ( mean [ + /-SE ] change in triceps area , 424 + /- 104 vs. -81 + /- 109 square millimeters ; P < 0.05 ) and legs ( change in quadriceps area , 607 + /- 123 vs. -131 + /- 111 square millimeters ; P < 0.05 ) and greater increases in strength in the bench-press ( 9 + /- 4 vs. -1 + /- 1 kg , P < 0.05 ) and squatting exercises ( 16 + /- 4 vs. 3 + /- 1 kg , P < 0.05 ) . The men assigned to testosterone and exercise had greater increases in fat-free mass ( 6.1 + /- 0.6 kg ) and muscle size ( triceps area , 501 + /- 104 square millimeters ; quadriceps area , 1174 + /- 91 square millimeters ) than those assigned to either no-exercise group , and greater increases in muscle strength ( bench-press strength , 22 + /- 2 kg ; squatting-exercise capacity , 38 + /- 4 kg ) than either no-exercise group . Neither mood nor behavior was altered in any group . CONCLUSIONS Supraphysiologic doses of testosterone , especially when combined with strength training , increase fat-free mass and muscle size and strength in normal men 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 Testosterone ( T ) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency , including improvement of sexual function , increase in muscle mass and strength , and decrease in fat mass , with minimal adverse effects . We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range . We now report the effects of 180 days of treatment with this 1 % T gel preparation ( 50 or 100 mg/day , contained in 5 or 10 g gel , respectively ) compared to those of a permeation-enhanced T patch ( 5 mg/day ) on defined efficacy parameters in 227 hypogonadal men . In the T gel groups , the T dose was adjusted up or down to 75 mg/day ( contained in 7.5 g gel ) on day 90 if serum T concentrations were below or above the normal male range . No dose adjustment was made with the T patch group . Sexual function and mood changes were monitored by question naire , body composition was determined by dual energy x-ray absorptiometry , and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises . Sexual function and mood improved maximally on day 30 of treatment , without differences across groups , and showed no further improvement with continuation of treatment . Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment . Moderate increases were also observed in arm/chest muscle strength . At 90 days of treatment , lean body mass increased more in the 100 mg/day T gel group ( 2.74 + /- 0.28 kg ; P = 0.0002 ) than in the 50 mg/day T gel ( 1.28 + /- 0.32 kg ) and T patch groups ( 1.20 + /- 0.26 kg ) . Fat mass and percent fat were not significantly decreased in the T patch group , but showed decreases in the T gel groups ( 50 mg/day , -0.90 + /- 0.32 kg ; 100 mg/day , - 1.05 + /- 0.22 kg ) . The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement . These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile . The increase in mean serum prostate-specific antigen levels ( within the normal range ) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group . Skin irritation was reported in 5.5 % of subjects treated with T gel and in 66 % of subjects in the permeation-enhanced T patch group . We conclude that T gel replacement improved sexual function and mood , increased lean mass and muscle strength ( principally in the legs ) , and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch BACKGROUND AND METHODS In order to assess the effects of testosterone undecanoate ( TU ; 120 mg/d orally for 2 months ) on serum lipid , lipoprotein , and apolipoprotein levels in healthy elderly men , the  placebo ( PL ) controlled study was performed on 37 elderly men , aged between 53 and 89 years . In all subjects venous blood sample s were taken after an overnight ( 10 hours ) fast and sera were stored -70 degrees C until analysis . RESULTS In PL group , neither hormonal data nor lipid , lipoprotein , and apolipoprotein levels showed significant changes . After TU supplementation , serum total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , and estradiol ( E2 ) levels decreased from 198 + /- 30.7 mg/dl to 174 + /- 41.9 mg/dl ( p < 0.05 ) , from 111 + /- 18.14 mg/dl to 87.9 + /- 29.4 mg/dl ( p < 0.01 ) , and from 86.2 + /- 16.9 pmol/l to 70.5 + /- 18 pmol/l ( p < 0.01 ) , respectively . Statistically significant differences were not observed in the serum triglyceride ( TG ) , high-density lipoprotein cholesterol ( HDL-C ) , and apolipoprotein ( apo ) A-1 and apo B levels after TU treatment . The mean ratios TC/HDL-C and LDL-C/HDL-C as coronary risk factor criteria decreased significantly in the TU but not in the PL group . No obvious side effect was observed in those who took TU except for reported pyrosis in 2 of 17 elderly men . CONCLUSIONS These data indicate that the increased serum levels of total testosterone ( TT ) produced by administration of TU , 120 mg/d orally for 2 months lead to suppressed levels of TC and LDL-C and E2 but not significantly changed levels of TC , HDL-C , apo A-1 and apo B. Thus , we conclude that TU may be an effective drug for protecting coronary heart disease in healthy elderly men with lowered TT and FT levels . It may also have beneficial effects for sexual function and behavior The AIDS wasting syndrome is characterized by loss of lean body mass out of proportion to weight [ 1 , 2 ] . The few effective treatments that have been identified are short-term pharmacologic agonists . Because loss of lean body mass is associated with decreased survival in men with the AIDS wasting syndrome [ 3 ] , development of therapeutic strategies to increase lean body mass is of critical importance . Half of all men with AIDS are hypogonadal [ 4 ] , and serum and rogen levels correlate with lean body mass among hypogonadal men with the AIDS wasting syndrome [ 5 ] . Previous studies in non-HIV-infected hypogonadal men show that and rogen administration has a significant anabolic effect on body composition [ 6 - 10 ] . We hypothesized that loss of the potent anabolic hormone testosterone in men with the AIDS wasting syndrome may contribute to the critical loss of lean body mass . Therefore , we investigated the effects of physiologic testosterone administration in men with the AIDS wasting syndrome . Methods Patients In 1995 and 1996 , 51 HIV-positive men ( 42 8 years of age ) were recruited from the multidisciplinary HIV practice at the Massachusetts General Hospital and from newspaper , television , and radio advertisements .  Weight , testosterone levels , and medication history were determined at a screening assessment . To be included in the study , patients had to have decreased free testosterone levels  , defined as less than 42 pmol/L at screening ( normal range for men 18 to 49 years of age , 42 to 121 pmol/L [ 12.0 to 35.0 pg/mL ] ) , and wasting , defined as weight less than 90 % of ideal body weight or involuntary weight loss greater than 10 % of baseline weight [ 11 ] . The CD4 count was not an inclusion criterion . We excluded patients with severe diarrhea ( > 6 stools/d ) ; hemoglobin value less than 5.0 mmol/L ( < 8 g/dL ) ; platelet count less than 50 000 cells/mm3 ; creatinine concentration greater than 177 mol/L ( > 2 mg/dL ) ; new opportunistic infection within 6 weeks of screening ; use of testosterone  , anabolic steroids , growth hormone , ketoconazole  , or  systemic steroid therapy within 3 months before screening ; or history of prostate cancer . In addition , patients receiving antiretroviral agents , including protease inhibitors , were required to be receiving a stable regimen for at least 6 weeks before study entry . Ten patients were receiving long-term , stable therapy with megestrol acetate for at least 8 weeks before study entry and were equally distributed between the two treatment groups ( 5 in the testosterone group and 5 in the placebo group ) . All patients gave written consent , and the study was approved by the Human Studies Committee of the Massachusetts General Hospital . Protocol Patients were r and omly assigned to receive testosterone enanthate , 300 mg ( Bio-Technology General Corp. , Iselin , New Jersey ) , or placebo intramuscularly every 3 weeks by self-injection . Participants were stratified for weight less than or greater than 90 % of ideal body weight and megestrol acetate use before r and omization . R and omization was performed by the Massachusetts General Hospital Pharmacy by using a permuted block algorithm . The correspondence between patient code number and drug was generated by the study statistician ; this list was available to the hospital pharmacist but not to the investigators or patients . The placebo contained sesame oil with chlorobutanol as a preservative and matched testosterone enanthate in color and consistency . The study drug was bottled by the Massachusetts General Hospital Pharmacy in containers labeled with the study name , expiration date , and patient code . Before the first injection , participants returned within approximately 2 weeks of the screening visit for a 3-day baseline inpatient visit to the General Clinical Research Center at the Massachusetts General Hospital for hormonal , nutritional , immune function , and body composition analysis , which included assessment by dual-energy x-ray absorptiometry , bioimpedance analysis , potassium-4040 K ) isotope analysis , and measurement of urinary creatinine excretion . No patient experienced the onset of a new opportunistic infection , other complication , or substantial weight change between the screening and baseline visits . Patients were instructed on the proper technique for intramuscular injection ; those who were unable to self-administer the study drug received injections every 3 weeks from the nursing staff of the General Clinical Research Center . Patients returned for an outpatient visit at 3 months for assessment of weight and determination of total-body potassium content and for a 3-day inpatient visit at 6 months ; this visit was identical to the baseline evaluation . Patients also reported on response to therapy at the 6-month visit . Baseline data from 26 patients have been reported elsewhere [ 5 ] . Subsequent study visits were timed to correspond to the midpoint between study drug injections . Study drug compliance was confirmed by history , medication diaries , outpatient injection records , empty vial counts , and serum testosterone levels . History of medication use was assessed at each visit . The change in fat-free mass assessed by dual-energy x-ray absorptiometry was the primary clinical end point ; changes in weight , muscle mass , total body potassium content , and quality of life were secondary end points . Body Composition Analysis Body composition was determined by four methods : 1 ) dual-energy x-ray absorptiometry to assess fat and fat-free mass ( Hologic-2000 densitometer , Hologic , Inc. , Waltham , Massachusetts ; precision error , 3 % for fat and 1.5 % for fat-free mass [ 12 ] , 2 ) 40 K isotope analysis to assess  total-body potassium content in a whole-body counter with sodium iodide detectors fixed above and below the patient at the xiphoid level ( Canberra Nuclear , Meriden , Connecticut ; precision error < 2.5 % on the basis of repeated calibration with a known potassium chloride source [ Appendix ] ) , 3 ) urinary creatinine excretion averaged over 3 days ( during which the patient received a meat-free diet ) multiplied by a constant of 18 kg of muscle per gram of urinary creatinine and indexed for height to determine the percentage of predicted muscle mass [ 13 , 14 ] , and 4 ) bioimpedance analysis to determine total-body water content ( Bioelectrical Impedance Analyzer Model BIA-101 , RJL Systems , Clinton Turnpike , Michigan ; correlation with deuterium oxide equivalent to R = 0.99 [ 15 ] ) . Lean body mass was derived from total-body potassium content by using the Equation of Forbes and Lewis of 68.1 mEq of potassium per kg of lean body mass [ 16 ] . Nutritional Assessment Weight was measured on the first day of each visit after an overnight fast . The percentage of ideal body weight was calculated on the basis of st and ard height and weight tables [ 17 ] . Patients were instructed on completion of a 4-day food record , which was analyzed for total calorie , fat , protein , and carbohydrate content ( Minnesota Nutrition Data Systems , version 8A/2.6 , Minneapolis , Minnesota ) by the Clinical Research Center dietitian . Patients received an isocaloric , meat-free , protein-substituted diet 3 days before and during the inpatient assessment s at baseline and at 6 months , during which creatinine excretion and nitrogen balance were measured . Total urinary nitrogen excretion was measured by the Kjeldal technique from consecutive 24-hour collection s averaged over 3 days . Nonurinary nitrogen losses were assumed to be constant at 4 g/d [ 13 , 18 , 19 ] . Nitrogen intake was derived from total protein intake divided by a constant of 6.25 g of protein per g of nitrogen [ 19 ] . Calorie and  protein  intake were monitored on a daily basis and were modified to match the reports in the outpatient food records immediately before these visits . Resting energy expenditure was measured by indirect calorimetry with a metabolic cart . Energy requirements were calculated by using the Harris-Benedict equation [ 20 ] . Patient Reports of Response to Therapy Each patient 's perceived well-being was assessed at the end of the study by using nine linear analogue-scale questions on the overall treatment effect , change in quality of life , personal appearance , weight , and appetite ( Table 1 ) [ 21 ] . A Karnofsky score was also determined at each visit . Table 1 . Assessment of Patient Response to Therapy * Exercise Functional Testing Exercise history was assessed by a st and ardized question naire adapted from the study by Kohl and coworkers [ 22 ] . Exercise functional status was determined at the baseline and final visits by the physical therapy department of the Massachusetts General Hospital by using the 6-minute walk test , the timed sit-to-st and test , and the timed get-up- and -go test [ 23 - 25 ] . The distance covered in 6 minutes , the number of times the patient was able to move from a sitting to st and ing position in 10 seconds , and the time to cover a distance of 3 meters after st and ing from a seated position was recorded for each patient . Biochemical and Immunologic Assays Hematocrit and serum levels of follicle-stimulating hormone , luteinizing hormone , sex hormone-binding globulin , and prolactin were measured at the baseline and final visits by using published methods [ 26 ] . Serum levels of total and free testosterone were measured by radioimmunoassay kit ( Diagnostics Products Corp. , Los Angeles , California ) with intra-assay coefficients of variation of 5 % to 12 % for total testosterone and 3.2 % to 4.3 % for free testosterone . CD4 cell counts were measured by flow cytometry ( Becton Dickinson Immunocytochemistry Systems , San Jose , California ) . Viral burden was determined by using the Amplicor HIV-1 monitor test ( Roche Molecular Systems , Branchburg , New Jersey ) . Statistical Analysis Sample size was based on the change in lean body mass in response to testosterone administration among adult men with acquired hypogonadism [ 8 ] . A change of 3.2 % 4.0 % was expected over 6 months . With 20 patients in each group , the study had an 80 % chance of seeing an effect of testosterone at a The present study examined lifestyle and behavioral correlates of the change in total testosterone over 13 years in 66 men aged 41 - 61 years who were former participants of the Multiple Risk Factor Intervention Trial ( MRFIT ) at the Pittsburgh , Pennsylvania , center . The authors also determined in these men if changes in total testosterone are related to changes in cardiovascular disease risk factors . The mean total testosterone level was 751 ( st and ard deviation , 248 ) ng/dl at baseline and decreased by 41 ( st and ard deviation , 314 ) ng/dl during follow-up . The correlation between measures was r = 0.44 ( p < 0.001 ) . In multivariate analysis , higher type A coronary-prone behavior score , greater pack-years of cigarette smoking , and the MRFIT special intervention group were associated with larger decreases in total testosterone . Age , body weight , weight change , leisure time activity level , and alcohol intake were not related to the change in total testosterone . The decrease in endogenous testosterone was associated with an increase in triglycerides and a decrease in high density lipoprotein cholesterol in multivariate analysis controlling for obesity and other lifestyle covariates . There was little relation between change in testosterone and change in total and low density lipoprotein cholesterol or blood pressure . This longitudinal study confirms a gradual decline in total testosterone levels with advancing age in older men and provides evidence that lifestyle and psychosocial factors are related to this decline . Decreases in endogenous testosterone levels with age in men are associated with potentially unfavorable changes in triglycerides and high density lipoprotein cholesterol Stanozolol , an oral 17 alpha-alkylated and rogen , increases hepatic triglyceride lipase activity ( HTGLA ) and decreases high-density lipoprotein cholesterol ( HDL-C ) levels , whereas intramuscular testosterone has comparatively little effect . In the present study , we tested the hypothesis that aromatization of and rogen to estrogen blunts the lipid and lipase effects of exogenous testosterone . Fourteen male weightlifters received testosterone enanthate ( 200 mg/wk intramuscularly ) , the aromatase inhibitor testolactone ( 250 mg four times per day ) , or both drugs together in a r and omized cross-over design . Serum testosterone level increased during all three drug treatments , whereas estradiol level increased only with testosterone alone ( + 47 % , P < .05 ) , demonstrating that testolactone effectively inhibited testosterone aromatization . Testosterone decreased HDL-C(-16 % , P < .05 ) , HDL2-C(-23 % , NS ) , and apoprotein ( apo ) A-I ( -12 % , P < .05 ) levels , effects that were consistently but not significantly greater with simultaneous testosterone and testolactone administration ( HDL-C , -20 % ; HDL2-C , -30 % ; apo A-I , -15 % ; P < .05 for all ) . In contrast , both testosterone regimens decreased HDL3-C levels by 13 % ( P < .05 for both ) . HTGLA increased 21 % during testosterone treatment and 38 % during combined testosterone and testolactone treatment ( P < .01 for both ) . Lipoprotein lipase activity ( LPLA ) increased only during combined testosterone and testolactone treatment ( + 31 % , P < .01 ) , suggesting that estrogen production may counteract the effects of testosterone on LPLA . Testolactone alone had little effect on any lipid , lipoprotein , apoprotein , or lipase concentration . ( ABSTRACT TRUNCATED AT 250 WORDS In a single-blind , placebo-controlled study , the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate ( And riol ® ) on the quality of life of men with testosterone deficiency were evaluated . The subjects included ten men with primary hypogonadism and 29 with and ropause with sexual dysfunction as the most common problem . The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Question naire for and rogen deficiency in aging males ( ADAM ) . Digital rectal examination ( DRE ) was performed and serum testosterone , prostate-specific antigen ( PSA ) and liver profile were monitored . Testosterone undecanoate treatment ( n = 33 ) significantly improved sexual dysfunction and symptom scores of metabolic , cardiopulmonary , musculo-skeletal and gastrointestinal functions compared to baseline and to placebo ( n = 6 ) . ADAM score also significantly improved after 3 months of treatment . Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group . In the placebo group , no significant changes compared to baseline were found for testosterone levels and QoL question naires . No abnormal findings were detected on DRE or laboratory findings in either group . Adverse events , such as gastrointestinal problems and fatigue , were mild and self-limiting . It is concluded that and rogen supplement therapy with oral testosterone undecanoate ( And riol ) restores the quality of life through improvement of general body functions in men with testosterone deficiency As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol .  Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer 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 Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months .  Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men PURPOSE Because the effects of and rogen replacement on lipoprotein levels are uncertain , we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men . SUBJECTS AND METHODS One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations > 1 SD below the mean for young men were r and omly assigned to receive either testosterone ( 54 men ; 6 mg/day ) or placebo ( 54 men ) transdermally in a double-blind fashion for 36 months . Serum concentrations of lipids and apolipoproteins were measured , and cardiovascular events recorded . RESULTS Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men , but the 3-year mean ( + /- SD ) decreases in the two groups ( testosterone treated , -17 + /- 29 mg/dL ; placebo treated , -12 + /- 38 mg/dL ) were not significantly different from each other ( P = 0.4 ) . Similarly , serum low-density lipoprotein ( LDL ) cholesterol levels decreased in both treatment groups , but the decreases in the two groups ( testosterone treated , -16 + /- 24 mg/dL ; placebo treated , -16 + /- 33 mg/dL ) were similar ( P = 1.0 ) . Levels of high-density lipoprotein ( HDL ) cholesterol , triglycerides , and apolipoproteins A-I and B did not change . Lipoprotein(a ) levels increased in both groups by similar amounts ( testosterone treated , 3 + /- 9 mg/dL ; placebo treated , 4 + /- 6 mg/dL ; P = 1.0 ) . The number of cardiovascular events was small and did not differ significantly between the  testosterone-treated  men ( 9 events ) and the placebo-treated men ( 5 events ) during the 3-year study ( relative risk = 1.8 ; 95 % confidence interval : 0.7 to 5.0 ) . CONCLUSIONS As compared with placebo , transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured . The effect of testosterone treatment on cardiovascular events was unclear , because the number of events was small Treatment of hypogonadal men with testosterone  has been shown to ameliorate the effects of testosterone deficiency on bone , muscle , erythropoiesis , and the prostate . Most previous studies , however , have employed somewhat pharmacological doses of testosterone esters , which could result in exaggerated effects , and /or have been of relatively short duration or employed previously treated men , which could result in dampened effects . The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density , muscle mass and strength , erythropoiesis , prostate volume , energy , sexual function , and lipids in previously untreated hypogonadal men . We selected 18 men who were hypogonadal ( mean serum testosterone + /- SD , 78 + /- 77 ng/dL ; 2.7 + /- 2.7 nmol/L ) due to organic disease and had never previously been treated for hypogonadism . We treated them with testosterone transdermally for 3 yr . Sixteen men completed 12 months of the protocol , and 14 men completed 36 months . The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment . Bone mineral density of the lumbar spine ( L2-L4 ) increased by 7.7 + /- 7.6 % ( P < 0.001 ) , and that of the femoral trochanter increased by 4.0 + /- 5.4 % ( P = 0.02 ) ; both reached maximum values by 24 months . Fat-free mass increased 3.1 kg ( P = 0.004 ) , and fat-free mass of the arms and legs individually increased , principally within the first 6 months . The decrease in fat mass was not statistically significant . Strength of knee flexion and extension did not change . Hematocrit increased dramatically , from mildly anemic ( 38.0 + /- 3.0 % ) to midnormal ( 43.1 + /- 4.0 % ; P = 0.002 ) within 3 months , and remained at that level for the duration of treatment . Prostate volume also increased dramatically , from subnormal ( 12.0 + /- 6.0 mL ) before treatment to normal ( 22.4 + /- 8.4 mL ; P = 0.004 ) , principally during the first 6 months . Self-reported sense of energy ( 49 + /- 19 % to 66 + /- 24 % ; P = 0.01 ) and sexual function ( 24 + /- 20 % to 66 + /- 24 % ; P < 0.001 ) also increased , principally within the first 3 months . Lipids did not change . We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip , fat-free mass , prostate volume , erythropoiesis , energy , and sexual function . The full effect of testosterone on bone mineral density took 24 months , but the full effects on the other tissues took only 3 - 6 months . These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men 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 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 CONTEXT Hormone administration to elderly individuals can increase lean body mass ( LBM ) and decrease fat , but interactive effects of growth hormone ( GH ) and sex steroids and their influence on strength and endurance are unknown . OBJECTIVE To evaluate the effects of recombinant human GH and /or sex steroids on body composition , strength , endurance , and adverse outcomes in aged persons . DESIGN , SETTING , AND PARTICIPANTS A 26-week r and omized , double-blind , placebo-controlled parallel-group trial in healthy , ambulatory , community-dwelling US women ( n = 57 ) and men ( n = 74 ) aged 65 to 88 years recruited between June 1992 and July 1998 . INTERVENTIONS Participants were r and omized to receive GH ( starting dose , 30 micro g/kg , reduced to 20 micro g/kg , subcutaneously 3 times/wk ) + sex steroids ( women : transdermal estradiol , 100 micro g/d , plus oral medroxyprogesterone acetate , 10 mg/d , during the last 10 days of each 28-day cycle [ HRT ] ; men : testosterone enanthate , biweekly intramuscular injections of 100 mg ) ( n = 35 ) ; GH + placebo sex steroid ( n = 30 ) ; sex steroid + placebo GH ( n = 35 ) ; or placebo GH + placebo sex steroid ( n = 31 ) in a 2 x 2 factorial design . MAIN OUTCOME MEASURES Lean body mass , fat mass , muscle strength , maximum oxygen uptake ( VO(2)max ) during treadmill test , and adverse effects . RESULTS In women , LBM increased by 0.4 kg with placebo , 1.2 kg with HRT ( P = .09 ) , 1.0 kg with GH ( P = .001 ) , and 2.1 kg with GH + HRT ( P<.001 ) . Fat mass decreased significantly in the GH and GH + HRT groups . In men , LBM increased by 0.1 kg with placebo , 1.4 kg with testosterone ( P = .06 ) , 3.1 kg with GH ( P<.001 ) , and 4.3 kg with GH + testosterone ( P<.001 ) . Fat mass decreased significantly with GH and GH + testosterone . Women 's strength decreased in the placebo group and increased nonsignificantly with HRT ( P = .09 ) , GH ( P = .29 ) , and GH + HRT ( P = .14 ) . Men 's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone ( P = .05 ) . Women 's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH ( P = .07 ) and GH + HRT ( P = .06 ) . Men 's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone ( P = .49 ) but increased with GH ( P = .11 ) and with GH + testosterone ( P<.001 ) . Changes in strength ( r = 0.355 ; P<.001 ) and in VO(2)max ( r = 0.320 ; P = .002 ) were directly related to changes in LBM . Edema was significantly more common in women taking GH ( 39 % vs 0 % ) and GH + HRT ( 38 % vs 0 % ) . Carpal tunnel symptoms were more common in men taking GH + testosterone ( 32 % vs 0 % ) and arthralgias were more common in men taking GH ( 41 % vs 0 % ) . Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH ( P = .006 ) . CONCLUSIONS In this study , GH with or without sex steroids in healthy , aged women and men increased LBM and decreased fat mass .  Sex steroid + GH increased muscle strength marginally and VO ( 2)max in men , but women had no significant change in strength or cardiovascular endurance . Because adverse effects were frequent ( importantly , diabetes and glucose intolerance ) , GH interventions in the elderly should be confined to controlled studies CONTEXT Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength . The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown . OBJECTIVE To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss . DESIGN AND SETTING Placebo-controlled , double-blind , r and omized clinical trial conducted from September 1995 to July 1998 at a general clinical research center . PARTICIPANTS Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L ( 349 ng/dL ) and weight loss of 5 % or more in the previous 6 months , 49 of whom completed the study . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : placebo , no exercise ( n = 14 ) ; testosterone enanthate ( 100 mg/wk intramuscularly ) , no exercise ( n = 17 ) ; placebo and exercise ( n = 15 ) ; or testosterone and exercise ( n = 15 ) . Treatment duration was 16 weeks . MAIN OUTCOME MEASURES Changes in muscle strength , body weight , thigh muscle volume , and lean body mass compared among the 4 treatment groups . RESULTS Body weight increased significantly by 2.6 kg ( P<.001 ) in men receiving testosterone alone and by 2.2 kg ( P = .02 ) in men who exercised alone but did not change in men receiving placebo alone ( -0.5 kg ; P = .55 ) or testosterone and exercise ( 0.7 kg ; P = .08 ) . Men treated with testosterone alone , exercise alone , or both experienced significant increases in maximum voluntary muscle strength in leg press ( range , 22%-30 % ) , leg curls ( range , 18%-36 % ) , bench press ( range , 19%-33 % ) , and latissimus pulls ( range , 17%-33 % ) . Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group . There was a greater increase in thigh muscle volume in men receiving testosterone alone ( mean change , 40 cm3 ; P<.001 vs zero change ) or exercise alone ( 62 cm3 ; P = .003 ) than in men receiving placebo alone ( 5 cm3 ; P = .70 ) . Average lean body mass increased by 2.3 kg ( P = .004 ) and 2.6 kg ( P<.001 ) , respectively , in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone ( 0.9 kg ; P = .21 ) . Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo . CONCLUSION Our data suggest that testosterone and resistance exercise promote gains in body weight , muscle mass , muscle strength , and lean body mass in HIV-infected men with weight loss and low testosterone levels . Testosterone and exercise together did not produce greater gains than either intervention alone The efficacy and safety of and rogen supplementation in older men remains controversial . Despite biochemical evidence of partial and rogen deficiency in older men , controlled studies using T demonstrate equivocal benefits . Furthermore , the importance of aromatization and 5alpha reduction in and rogen actions among older men remains unclear . Dihydrotestosterone is the highest potency natural and rogen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction . Therefore , the effects of dihydrotestosterone may differ from those of T in older men . This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength , mobility , and quality of life in ambulant , community-dwelling men aged 60 yr or older . Eligible men ( plasma T < or = 15 nmol/liter ) were r and omized to undergo daily dermal application of 70 mg dihydrotestosterone gel ( n = 18 ) or vehicle ( n = 19 ) and were studied before , monthly during , and 1 month after treatment . Among 33 ( 17 dihydrotestosterone , 16 placebo ) men completing the study with a high degree of compliance , dihydrotestosterone had significant effects on circulating hormones ( increased dihydrotestosterone ; decreased total and free testosterone , LH , and FSH ; unchanged SHBG and estradiol ) , lipid profiles ( decreased total and low-density lipoprotein cholesterols ; unchanged high-density lipoprotein cholesterol and triglycerides ) , hematopoiesis ( increased hemoglobin , hematocrit , and red cell counts ) , and body composition ( decreased skinfold thickness and fat mass ; unchanged lean mass and waist to hip ratio ) . Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction , nor was there any significant change in gait , balance , or mobility tests , in cognitive function , or in quality of life scales .  Dihydrotestosterone treatment had no adverse effects on prostate ( unchanged prostate volumes and prostate-specific antigen ) and cardiovascular ( no adverse change in vascular reactivity or lipids ) safety markers . We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected and rogenic effects , short-term safety , and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function CONTEXT Patients receiving dialysis commonly experience malnutrition , reduced muscle mass ( sarcopenia ) , and fatigue for which no effective treatment has been identified . Anabolic steroids are known to increase muscle mass and strength in healthy individuals , but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated . OBJECTIVE To assess the effects of an anabolic steroid , n and rolone decanoate , on lean body mass ( LBM ) , functional status , and quality of life in dialysis patients . DESIGN R and omized , double-blind , placebo-controlled trial conducted between April 1996 and July 1997 . SETTING Hospital-based outpatient dialysis unit . PATIENTS Twenty-nine patients undergoing dialysis for at least 3 months . INTERVENTION N and rolone decanoate , 100 mg ( n = 14 ) , or placebo ( n = 15 ) by intramuscular injection once a week for 6 months . MAIN OUTCOME MEASURES Weight , LBM , fatigue , grip strength , walking and stair-climbing times , and treadmill performance after 3 and 6 months of treatment . RESULTS Lean body mass increased significantly in patients given n and rolone compared with patients given placebo ( mean change [ SD ] , + 4.5 [ 2.3 ] kg ; P<.001 compared with baseline ) . This effect was significantly greater than the change in LBM in the placebo group ( mean change [ SD ] , + 1.9 [ 1.6 ] kg ; P = .003 compared with baseline ; P = .005 compared with n and rolone group ) . Serum creatinine levels increased in the n and rolone group ( + 168 [ 203 ] mmol/L [ 1.9 [ 2.3 ] mg/dL ] ; P = .02 ) but not in the placebo group ( -4.0 [ 177 ] mmol/L [ 0.04 [ 2.0 ] mg/dL ] ; P = .95 ) , suggesting an increase in muscle mass . Time to complete the walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the n and rolone group , while those in the placebo group increased from 38.7 to 42.1 seconds ( P = .05 ) . Peak oxygen consumption increased in the individuals in the n and rolone group who performed treadmill tests , but not to a statistically significant degree . Grip strength did not change in either group . CONCLUSIONS Treatment with n and rolone for 6 months result ed in a significant increase in LBM associated with functional improvement in patients undergoing dialysis
target: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men .
background: OBJECTIVES Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass , accumulation of central adiposity , impaired mobility and increased risk of bone fractures .
  Whether and rogen treatment might be beneficial in these subjects is still under debate .
  We have carried out a systematic review of r and omized controlled trials ( RCTs ) evaluating the effects of testosterone ( T ) administration  to middle-aged and ageing men on body composition , muscle strength , bone density , markers of bone metabolism and serum lipid profile .