Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus. Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With Chronic Stable Angina: A Randomized, Double-Blind, Placebo-Controlled Study Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Adverse events associated with testosterone administration. Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Testosterone therapy increased muscle mass and lipid oxidation in aging men Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. 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. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. A double-blind, placebo-controlled, randomized clinical trial of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment
AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels .  Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure CONTEXT Cycling and rogens has been reported by athletes to improve physical performance by enhancing muscle mass and strength , a paradigm that has not been studied , and may have clinical value in older men being treated with testosterone .  OBJECTIVE We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current st and ard of care continuous therapy on body composition and muscle strength in older men . DESIGN , SETTING , AND PATIENTS Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were r and omized at the Institute for Translational Sciences- Clinical Research Center into a 5-month double-blind placebo-controlled trial . INTERVENTION Subjects were dosed weekly for 5 months , receiving continuous testosterone ( TE , n = 8 ; 100 mg testosterone enanthate , i m injection ) , monthly cycled testosterone ( MO , n = 8 ; alternating months of testosterone and placebo ) , or placebo ( PL , n = 8) . MAIN OUTCOME MEASURES Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength . Secondary outcomes included body weight , serum hormones , and mixed-muscle protein fractional synthesis rate ( FSR ) . RESULTS Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO ( P < 0.05 ) . Upper body muscle strength increased in TE , and lower body muscle strength increased in TE and MO ( P < 0.05 ) . FSR increased in TE and MO ( P < 0.05 ) but not in PL . CONCLUSIONS Cycled testosterone  improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone OBJECTIVES And rogen deficiency has been associated with the development of systemic lupus erythematosus ( SLE ) . The aim of this study was to test the efficacy of testosterone patches vs placebo in female SLE patients with baseline mild-to-moderate disease activity in a r and omized , double-blind , single-centre placebo-controlled trial . METHODS Patients received testosterone ( 150 microg ) or placebo transdermal patches for 12 weeks . Patients were assessed at 4-weekly intervals for disease activity using the Safety of Oestrogens in Lupus Erythematosus National Assessment -SLE Disease Activity Index ( SELENA-SLEDAI ) , Systemic Lupus Activity Measure-Revised ( SLAM-R ) and The British Isles Lupus Assessment Group ( BILAG ) indices , physician global assessment ( PGA ) , quality of life using the SF-36 survey and sexual functioning using the Derogatis score . Data were analysed using two sample t-tests to compare the mean difference from baseline to week 12 in the testosterone patch and placebo groups . RESULTS Thirty-four patients were recruited in to each group . There was no significant baseline difference between the groups in age , race or marital status . There was no significant difference between treatment groups in the mean change in SELENA-SLEDAI ( 0.547 + /- 3.72 , P > 0.60 ) , nor in PGA or BILAG system scores . The mean change in SLAM-R score was statistically different ( 2.06 , S.D. 3.3 , P = 0.01 ) but was not considered clinical ly meaningful . Health transition also showed a small change ( P < 0.03 ) . There was no significant difference in the Derogatis scores or toxicity . CONCLUSIONS Testosterone patches were safe but did not significantly affect disease activity , quality of life or sexual functioning . Increased use of steroids in the placebo group may have confounded the study results Background Experimental studies suggest that and rogens induce coronary vasodilatation . We performed this pilot project to examine the clinical effects of long-term low-dose and rogens in men with angina . Methods and Results Forty-six men with stable angina completed a 2-week , single-blind placebo run-in , followed by double-blind r and omization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks , in addition to their current medication . Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment . Active treatment result ed in a 2-fold increase in and rogen levels and an increase in time to 1-mm ST-segment depression from ( mean±SEM ) 309±27 seconds at baseline to 343±26 seconds after 4 weeks and to 361±22 seconds after 12 weeks . This change was statistically significant compared with that seen in the placebo group ( from 266±25 seconds at baseline to 284±23 seconds after 4 weeks and to 292±24 seconds after 12 weeks;P = 0.02 between the 2 groups by ANCOVA ) . The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone ( r = −0.455 , P < 0.05 ) . There were no significant changes in prostate specific antigen , hemoglobin , lipids , or coagulation profiles during the study . There were significant improvements in pain perception ( P = 0.026 ) and role limitation result ing from physical problems ( P = 0.024 ) in the testosterone-treated group . Conclusions Low-dose supplemental testosterone treatment in men with chronic stable angina  reduces exercise-induced myocardial ischemia BACKGROUND Hypogonadism and anemia are common comorbid conditions in dialysis patients .  Testosterone replacement may improve such clinical parameters as anemia , sarcopenia , and low libido . Additionally , by increasing hemoglobin levels , testosterone replacement may allow for a dose reduction in recombinant human erythropoietin ( rHuEPO ) , thereby reducing cost . METHODS This phase IV , single-center , placebo-controlled , double-blind study assessed the effect of transdermal testosterone on serum testosterone levels , rHuEPO dose required to maintain hemoglobin level , bone mineral content , lean body mass and fat content , cholesterol level , sexual function , and mood . Forty hypogonadal male hemodialysis patients who were administered rHuEPO were r and omly assigned to 100 mg of topical 1 % testosterone gel ( Testim ; Auxilium Pharmaceuticals , Norristown , PA ) or placebo , applied daily for 6 months . RESULTS Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL ( < 10.4 nmol/L ) participated in this trial . In men assigned to administration of transdermal testosterone , there was an increase beyond that in the placebo group in mean serum testosterone ( 77.1 ng/dL [ 2.7 nmol/L ] ) , dihydrotestosterone ( DHT ; 0.8 nmol/L ) , and estradiol levels ( 6.3 pg/mL [ 23.0 pmol/L ] ) and a decrease in mean serum luteinizing hormone levels ( -3.1 IU/L ) . Compared with subjects administered placebo , participants on testosterone replacement therapy did not show an appreciable change in  rHuEPO dose ( mean difference adjusted for baseline values , 12.6 U/kg/wk ; P = 0.73 ) , bone mineral density , lean body mass or fat content , cholesterol level , sexual function , or mood . CONCLUSION Daily administration of 100 mg of topical 1 % testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease . Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study . Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease 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 . Although decline in sexual function is a common reason for ageing men to seek advice regarding testosterone therapy , placebo-controlled trial data have been unable to show a consistent , beneficial role for testosterone . The objective of this study was to determine the effect of testosterone therapy on sexual function in non-obese ageing men with symptoms of and rogen deficiency and low – normal serum testosterone levels . A total of 60 men aged 55 years or older in good general health with total testosterone ( TT ) levels < 15 nM , and with symptoms suggestive of and rogen deficiency , were r and omized in a double-blinded protocol to transdermal testosterone patches or placebo for 12 months  . Sexual function was assessed using the International Index of Erectile Function at weeks 0 , 26 and 52 . In men receiving testosterone TT levels increased by 30 % ( P=0.01 ) and luteinizing hormone decreased by 50 % ( P<0.001 ) . Relative to placebo , testosterone therapy improved sexual desire ( P=0.04 ) ; however other parameters of sexual function including erectile function were unaffected by the treatment . Ageing men in good general health and with symptoms of and rogen deficiency and low – normal serum testosterone levels receiving 12 months of transdermal testosterone therapy experienced , relative to placebo , improved sexual desire but no effect on other parameters of sexual function 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 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 Testosterone ( T ) therapy in older men with low serum T levels increases lean body mass and decreases fat mass . These changes might improve physical performance and strength ; however , it has not been established whether T therapy improves functional outcome in older men . Moreover , concerns exist about the impact of T therapy on the prostate in older men . The administration of finasteride ( F ) , which partially blocks the conversion of T to the more potent and rogen , dihydrotestosterone , attenuates the impact of T replacement on prostate size and prostate-specific antigen . We hypothesized that T replacement in older , hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance , strength , and body composition . Seventy men with low serum T ( < 350 ng/dl ) , age 65 yr and older , were r and omly assigned to receive one of three regimens for 36 months : 1 ) T enanthate , 200 mg i m every 2 wk , with placebo pills daily ( T-only ) ; 2 ) T enanthate , 200 mg every 2 wk , with 5 mg F daily ( T + F ) ; or 3 ) placebo injections and pills ( placebo ) . We obtained serial measurements of timed physical performance , grip strength , lower extremity strength , body composition ( by dual-energy x-ray absorptiometry ) , fasting cholesterol profiles , and hormones .  Fifty men completed the 36-month protocol . After 36 months , T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 + /- 1.6 % ( mean + /- sem , T-only ) and 3.8 + /- 1.0 % ( T + F ) vs. -5.6 + /- 1.9 % for placebo ( P < 0.002 for both T and T + F vs. placebo ) ] and increased h and grip strength compared with baseline and placebo ( P < 0.05 ) . T therapy increased lean body mass [ 3.77 + /- 0.55 kg ( T-only ) and 3.64 + /- 0.56 kg ( T + F ) vs. -0.21 + /- 0.55 kg for placebo ( P < 0.0001 ) ] , decreased fat mass , and significantly decreased total cholesterol , low-density lipoprotein , and leptin , without affecting high-density lipoprotein , adiponectin , or fasting insulin levels . These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months , when administered alone or when combined with F , and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men CONTEXT Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and and rogenic alopecia , but the role of 5α-dihydrotestosterone ( DHT ) in mediating testosterone 's effects on muscle , sexual function , erythropoiesis , and other and rogen-dependent processes remains poorly understood . OBJECTIVE To determine whether testosterone 's effects on muscle mass , strength , sexual function , hematocrit level , prostate volume , sebum production , and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride ( an inhibitor of 5α-reductase type 1 and 2 ) . DESIGN , SETTING , AND PATIENTS The 5α-Reductase Trial was a r and omized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010 . INTERVENTIONS Eight treatment groups received 50 , 125 , 300 , or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo ( 4 groups ) or 2.5 mg/d of dutasteride ( 4 groups ) . MAIN OUTCOME MEASURES The primary outcome was change in fat-free mass ; secondary outcomes : changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels . RESULTS A total of 139 men were r and omized ; 102 completed the 20-week intervention . Men assigned to dutasteride were similar at baseline to those assigned to placebo . The mean fat-free mass gained by the dutasteride groups was 0.6 kg ( 95 % CI , -0.1 to 1.2 kg ) when receiving 50 mg/wk of testosterone enanthate , 2.6 kg ( 95 % CI , 0.9 to 4.3 kg ) for 125 mg/wk , 5.8 kg ( 95 % CI , 4.8 to 6.9 kg ) for 300 mg/wk , and 7.1 kg ( 95 % CI , 6.0 to 8.2 kg ) for 600 mg/wk . The mean fat-free mass gained by the placebo groups was 0.8 kg ( 95 % CI , -0.1 to 1.7 kg ) when receiving 50 mg/wk of testosterone enanthate , 3.5 kg ( 95 % CI , 2.1 to 4.8 kg ) for 125 mg/wk , 5.7 kg ( 95 % CI , 4.8 to 6.5 kg ) for 300 mg/wk , and 8.1 kg ( 95 % CI , 6.7 to 9.5 kg ) for 600 mg/wk . The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant ( P = .18 ) . Changes in fat mass , muscle strength , sexual function , prostate volume , sebum production , and hematocrit and lipid levels did not differ between groups . CONCLUSION Changes in fat-free mass in response to grade d testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo , indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00493987 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 BACKGROUND Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass ( FFM ) and skeletal muscle and decreases in fat mass ( FM ) but have not reported the impact of baseline body composition . OBJECTIVE The objective of the study was to determine the effect , in nonobese aging men with symptoms of and rogen deficiency and low-normal serum testosterone levels , of testosterone therapy on total and regional body composition and hormonal and metabolic indices . METHODS Sixty healthy but symptomatic , nonobese men aged 55 yr or older with total testosterone ( TT ) levels less than 15 nm were r and omized to transdermal testosterone patches or placebo for 52 wk . Body composition , by dual-energy x-ray absorptiometry ( FM , FFM , skeletal muscle ) and magnetic resonance imaging ( abdominal sc and visceral adipose tissue , thigh skeletal muscle , and intermuscular fat ) and hormonal and metabolic parameters were measured at wk 0 and 52 . RESULTS Serum TT increased by 30 % ( P = 0.01 ) , and LH decreased by 50 % ( P < 0.001 ) . Relative to placebo , total body FFM ( P = 0.03 ) and skeletal muscle ( P = 0.008 ) were increased and thigh skeletal muscle loss was prevented ( P = 0.045 ) with testosterone therapy and visceral fat accumulation decreased ( P = 0.001 ) without change in total body or abdominal sc FM ; change in visceral fat was correlated with change in TT levels ( r2 = 0.36 ; P = 0.014 ) . There was a trend to increasing total and low-density lipoprotein cholesterol with placebo . CONCLUSION Testosterone therapy , relative to placebo , selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass . Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk 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 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 Despite partial and rogen deficiency , the safety and efficacy of  and rogen therapy in older men remains controversial because controlled studies of testosterone have given equivocal results . Human chorionic gonadotropin ( hCG ) can be conveniently and infrequently self-administered , and it increases not only circulating testosterone but also estradiol and other testicular steroids . We evaluated the efficacy and safety of 3 months of treatment with sc recombinant hCG ( r-hCG , Ovidrel ) on muscle mass , strength , mobility , and physical activity in ambulant , community-dwelling men more than 60 yr old having partial and rogen deficiency ( testosterone < or = 15 nmol/liter , twice ) . Forty eligible men ( mean age , 67 yr ; range , 60 - 85 yr ) were r and omized to receive r-hCG ( 5000 IU , 250 microg ) or placebo by twice weekly sc self-injection and were studied before treatment , monthly during treatment , and 1 month after treatment . All completed the study , and treatment groups were well matched . r-hCG significantly increased body weight ( approximately 1 kg ; P < 0.05 ) and lean body mass ( approximately 2 kg ; P < 0.001 ) and reduced fat mass ( approximately 1 kg , P < 0.05 ) . However , anthropometric measures of skinfold thickness ( biceps , triceps , subscapular , suprailiac ) and circumferences ( midarm , waist , hip , and midthigh ) , including the waist-hip ratio , did not change significantly . Shoulder and knee strength ( peak torque ) , as measured by isokinetic and isometric dynamometry , was not significantly increased , nor was physical activity ( accelerometry and Physical Activity Scale for Elderly self-report ) or gait and balance ( modified Guralnik and Frailty and Injuries : Cooperative Studies of Intervention Techniques performance batteries ) altered . Total and free testosterone and estradiol were markedly ( 150 % ; P < 0.001 ) and stably increased , whereas LH , FSH , and urea were significantly decreased . Testis volume was significantly decreased ( approximately 5 ml ; P < 0.05 ) . There were no significant changes in hemoglobin , osteocalcin , or prostate-specific antigen , and the International Prostate Symptom Score did not change . Three men developed nipple tenderness that did not progress to gynecomastia . We conclude that 3 months of treatment with twice weekly r-hCG demonstrates sustained and rogenic effects on hormones and muscle mass but has no effect on muscle strength or physical functioning Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men . We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed , hypogonadal men . For this study , we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower . We r and omized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen . The primary outcome measure was the Hamilton Depression Rating Scale ( HDRS ) score . Secondary measures included the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impression Scale , and the Quality of Life Scale . Our primary analysis , using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures , failed to show a significant difference between groups ( mean [ 95 % confidence interval ] 6-week change in HDRS for testosterone vs placebo , −0.4 [ −2.6 to 1.8 ] ) . However , in one exploratory analysis of treatment responders , we found a possible trend in favor of testosterone on the HDRS . Our findings , combined with the conflicting data from earlier smaller studies , suggest that testosterone is not generally effective for depressed men . The possibility remains that testosterone might benefit a particular subgroup of depressed men , but if so , the characteristics of this subgroup would still need to be established
Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding .
Nevertheless , overall and particularly in trials not funded by the pharmaceutical industry , exogenous testosterone increased the risk of cardiovascular-related events , with corresponding implication s for the use of testosterone therapy
Background Testosterone therapy is increasingly promoted .
No r and omized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events , although very high levels of and rogens are thought to promote cardiovascular disease .