title: The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Testosterone Replacement in Androgen-Deficient Men With Ejaculatory Dysfunction: A Randomized Controlled Trial. Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients. Effects of testosterone on mood, aggression, and sexual behavior in young men: a double-blind, placebo-controlled, cross-over study. The effect of testosterone on health-related quality of life in elderly males - a pilot study. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Effects of testosterone supplementation in the aging male. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Testosterone Treatment of Men With Mild Cognitive Impairment and Low Testosterone Levels Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Testosterone Administration Decreases Generosity in the Ultimatum Game Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. The effects of exogenous testosterone on sexuality and mood of normal men. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Pharmacokinetic characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: a pilot study. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Activational effects of testosterone on cognitive function in men Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease Effect of testosterone cypionate on postexercise ST segment depression. Sex Steroids Modify Working Memory Effect of testosterone treatment on bone mineral density in men over 65 years of age. Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function. Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With Chronic Stable Angina: A Randomized, Double-Blind, Placebo-Controlled Study Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. Relationship between testosterone supplementation and insulin-like growth factor-I levels and cognition in healthy older men Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. 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 and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with chronic stable angina. Adverse events associated with testosterone administration. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Therapeutic Effects of Nandrolone and Testosterone in Adult Male HIV Patients With AIDS Wasting Syndrome (AWS): A Randomized, Double-Blind, Placebo-Controlled Trial A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. Effect of testosterone supplementation on sexual functioning in aging men: a 6-month randomized controlled trial A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. Beneficial effects of testosterone undecanoate on the lipoprotein profiles in healthy elderly men. A placebo controlled study. Testosterone influences spatial cognition in older men. Effects of Androgen Administration in Men with the AIDS Wasting Syndrome Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men--a clinical research center study. Increased aggressive responding in male volunteers following the administration of gradually increasing doses of testosterone cypionate. Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting. Intramuscular Testosterone Supplementation to Selective Serotonin Reuptake Inhibitor in Treatment-Resistant Depressed Men: Randomized Placebo-Controlled Clinical Trial Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Effects of testosterone undecanoate on sexual potency and the hypothalamic-pituitary-gonadal axis of impotent males Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). Effects of muscle strength training and testosterone in frail elderly males. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Effect of oral testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Testosterone supplementation improves spatial and verbal memory in healthy older men The role of aromatization in testosterone supplementation Safety and Efficacy of Testosterone Gel 1% Augmentation in Depressed Men With Partial Response to Antidepressant Therapy A trial of testosterone therapy for HIV‐associated weight loss Effect of Testosterone Administration on Sexual Behavior and Mood in Men with Erectile Dysfunction Randomized controlled trial of testosterone in myotonic dystrophy Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency Oral testosterone supplementation and chronic low-grade inflammation in elderly men: a 26-week randomized, placebo-controlled trial. Efficacy of testosterone, trazodone and hypnotic suggestion in the treatment of non-organic male sexual dysfunction. Testosterone treatment and mortality in men with low testosterone levels. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status. Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Chronic testosterone cypionate therapy in men with secondary impotence. Effects of androgen on sexual behavior in hypogonadal men. The Sexual Effects of Testosterone Replacement in Depressed Men: Randomized, Placebo-Controlled Clinical Trial Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Acute haemodynamic effects of testosterone in men with chronic heart failure. Effects of Oral Testosterone Treatment on Myocardial Perfusion and Vascular Function in Men With Low Plasma Testosterone and Coronary Heart Disease ANDROGEN REPLACEMENT WITH ORAL TESTOSTERONE UNDECANOATE IN HYPOGONADAL MEN: A DOUBLE BLIND CONTROLLED STUDY Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. Randomized placebo‐controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. Testosterone treatment improves body composition and sexual function in men with COPD, in a 6-month randomized controlled trial. Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men. The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection. DHEA in elderly women and DHEA or testosterone in elderly men. Changes in lipoprotein-lipid levels in normal men following administration of increasing doses of testosterone cypionate. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. Testosterone improves rehabilitation outcomes in ill older men. Testosterone Gel Replacement Improves Sexual Function in Depressed Men Taking Serotonergic Antidepressants: A Randomized, Placebo-Controlled Clinical Trial Testosterone Versus Fluoxetine for Depression and Fatigue in HIV/AIDS: A Placebo-Controlled Trial Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease. Testosterone Therapy in Obliterating Arterial Lesions in the Lower Limbs 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. Effects of Testosterone Replacement in Middle-Aged Men With Dysthymia: A Randomized, Placebo-Controlled Clinical Trial Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Effect of Testosterone Replacement on Response to Sildenafil Citrate in Men With Erectile Dysfunction
abstract: Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol .  Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease CONTEXT Low T levels have been associated with  ejaculatory dysfunction ( EjD ) in cross-sectional studies ; however , the efficacy of T replacement in improving EjD has not been studied in a r and omized controlled trial . OBJECTIVE To evaluate the efficacy of T replacement in and rogen-deficient men with EjD. DESIGN A multicenter , double-blind , r and omized , placebo-controlled , 16-week trial with T solution 2 % versus placebo . SETTING Medical centers in the United States , Canada , and Mexico . PATIENTS OR OTHER PARTICIPANTS Seventy-six men with one or more EjD symptoms , including delayed ejaculation , anejaculation , reduced ejaculate volume , and /or reduced force of ejaculation , and two total T levels < 300 ng/dL ( < 10.41 nmol/L ) measured with liquid chromatography t and em mass spectrometry . INTERVENTIONS Sixty milligrams of T solution 2 % or placebo applied to the axillae for 16 weeks . MAIN OUTCOME MEASURES The primary outcome was a change in the score of the three-item Male Sexual Health Question naire-Ejaculatory Dysfunction-Short Form ( MSHQ-EjD-SF ) ; secondary outcomes included measured ejaculate volume , scores of the bother/satisfaction item of the MSHQ-EjD-SF , the orgasmic function domain of the International Index of Erectile Function Question naire , and the sexual activity log . RESULTS Seventy-six participants were r and omized ; 66 completed the study . Baseline demographic and clinical characteristics were comparable between the treatment arms . T replacement improved the MSHQ-EjD-SF score ( mean score change , + 3.1 ) ; however , this effect was not statistically different from placebo ( mean score change , + 2.5 ; P = .596 ) . No differences were seen in any of the secondary outcomes or frequency of adverse events . CONCLUSION T replacement was not associated with significant improvement in EjD in and rogen-deficient men Objective —Because male sex is an independent risk factor for the severity of atherosclerosis , it is possible that and rogens may be proatherogenic . There is evidence that sex hormones , particularly estrogens , regulate ( or modulate ) inflammation , a process integral to atherogenesis . Because levels of serum inflammatory markers predict cardiovascular outcomes , we prospect ively assessed the effects of and rogen therapy on these markers in older men . Methods and Results —Levels of high-sensitivity C-reactive protein ( CRP ) , soluble intracellular adhesion molecule-1 ( sICAM-1 ) , and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) were measured from sera collected at baseline and at the end of 2 r and omized double-blind placebo-controlled trials evaluating the effects of 3 months of and rogen treatment with either dihydrotestosterone ( DHT ) or recombinant human chorionic gonadotropin ( rhCG ) in healthy men aged > 60 years with partial and rogen deficiency ( serum testosterone levels < 15 nmol/L ) . For the DHT study ( 70 mg transdermally daily ) , 33 men completed 3 months of treatment ( 16 men were treated with DHT , and there were 17 controls ) . For the rhCG ( 250 & mgr;g twice weekly ) study , 20 men were treated with rhCG , and there were 20 controls . In both studies , groups were well matched for age and vascular risk factors . And rogen levels ( DHT and testosterone ) were consistently maintained at eugonadal levels throughout the trials , with estradiol markedly increased by rhCG but not DHT .  Baseline CRP levels were 0.74 to 1.49 mg/L , sVCAM-1 levels were 847 to 950 ng/mL , and sICAM-1 levels were 256 to 292 ng/mL in all groups . Neither DHT nor rhCG result ed in significant changes in CRP , sVCAM-1 , or sICAM-1 compared with placebo ( P > 0.3 in both studies ) . Conclusions —Exogenous and rogen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men ; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women . These data provide a measure of reassurance concerning potential adverse cardiovascular effects of and rogen therapy in older men CONTEXT Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation . Trial 's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm . The changes in muscle performance and physical function were evaluated in relation to participant 's perception of change . METHODS Men aged 65 years and older , with mobility limitation , total testosterone 100 - 350 ng/dL , or free testosterone less than 50 pg/mL , were r and omized to placebo or 10 g testosterone gel daily for 6 months . Primary outcome was leg-press strength . Secondary outcomes included chest-press strength , stair-climb , 40-m walk , muscle mass , physical activity , self-reported function , and fatigue . Proportions of participants exceeding minimally important difference in study arms were compared . RESULTS Of 209 r and omized participants , 165 had follow-up efficacy measures . Mean ( SD ) age was 74 ( 5.4 ) years and short physical performance battery score 7.7 ( 1.4 ) .  Testosterone arm exhibited greater improvements in leg-press strength , chest-press strength and power , and loaded stair-climb than placebo . Compared with placebo , significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths ( 43 % vs 18 % , p = .01 ) and stair-climbing power ( 28 % vs 10 % , p = .03 ) more than minimally important difference . Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass . Physical activity , walking speed , self-reported function , and fatigue did not change . CONCLUSIONS Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power . Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population The elevated estradiol/testosterone ( E2/T ) ratio had been proved to be a risk factor for coronary heart disease ( CHD ) in elderly men . We conducted a r and omized placebo controlled crossover study on the effects of a new and rogenic preparation " And riol " in 62 elderly men with CHD over a period of 2.5 months . The results showed significant differences between And riol- and placebo-treated groups at the end of this period : in the former , serum T level was elevated significantly ( P < 0.001 ) , E2 level was unchanged ( P > 0.05 ) , E2/T ratio was reduced ( P < 0.05 ) , angina pectoris ( AP ) was relieved ( total effective rate , 77.4 % ) , and myocardial ischemia in ECG and Holter recordings were improved ( total effective rate , respectively 68.8 % and 75 % ) . Doppler echocardiography showed that 12 parameters of cardiac function were unchanged in both groups . No obvious side effect was found in those who took And riol The prospect s of wider application of testosterone ( T ) in novel indications such as male contraception have prompted renewed interest in the investigation of nonreproductive actions and safety of and rogens . This study investigated potential changes in mood and behavior in response to elevations in circulating T concentrations produced by the new long-acting preparation , T undecanoate ( TU ) .  Twenty-eight eugonadal men were r and omized into one of two treatment groups : A1 ) active , receiving 1000 mg TU i.m . followed by A2 ) washout , followed by A3 ) placebo , receiving 4 ml castor oil i.m . ; B1 ) placebo , 4 ml castor oil i.m . ; B2 ) washout followed by B3 ) active , receiving 1000 mg TU i.m .. Mood , self- and partner-reported physical and verbal aggression , anger , hostility , irritability , assertiveness , self-esteem , and sexual function were assessed . A single injection of 1000 mg TU i.m . increased plasma T concentrations from 20.7 + /- 1.5 to 37.5 + /- 2.2 nmol/liter at wk 1 and 31.6 + /- 1.5 nmol/liter at wk 2 , and estradiol from 74.0 + /- 4.9 to 120.4 + /- 10.7 pmol/liter at wk 1 , and 100.0 + /- 6.3 pmol/liter at wk 2 . The T increment was associated with detectable but minor mood changes . Increased circulating T was associated with significant increases in anger-hostility from baseline ( mean score = 7.48 ) to wk 2 ( mean score = 10.71 ) accompanied by an overall reduction in fatigue-inertia ( treatment = 6.21 vs. placebo = 7.84 ) . TU treatment did not increase aggressive behavior or induce any changes in nonaggressive or sexual behavior . Changes in estradiol were not associated with any behavioral alterations . Our results suggest that exogenous TU-induced elevation of circulating T , to the range likely to be used in hormonal male contraception , has limited psychological effects . Future research should investigate the implication s of these minor mood changes OBJECTIVE To assess the effect of short-term testosterone supplementation on health-related quality of life in elderly males . METHOD As part of a double-blind , placebo-controlled study , healthy males > or = 65-year-old were r and omised to receive a total of four doses of 200 mg testosterone enanthanate ( n = 14 ) or placebo ( n = 8) intramuscularly every 2 weeks . Health-related quality of life ( HRQOL ) was assessed using the Short Form 36-item ( SF-36 ) and Psychological General Well-Being ( PGWB ) scales , at baseline , week 8 and during therapy withdrawal , 6 weeks after the last dose . RESULTS The baseline SF-36 scores were similar between the groups in seven domains ; only vitality was significantly lower in the placebo group ( T : 80.4 , P : 65.6 ; P = 0.007 ) . After the 8-week treatment period and withdrawal phase , SF-36 scores were not significantly different between the groups . The PGWB scores at baseline , on treatment and off treatment were not significantly different between the groups . Moreover , the SF-36 and PGWB scores within each group did not change significantly over time . CONCLUSION This pilot study suggests that intramuscular testosterone , administered at a dose of 200 mg every 2 weeks , does not affect the HRQOL of elderly males OBJECTIVE Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men . Furthermore , there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men . Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance . We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein ( CRP ) in type 2 diabetic men . DESIGN Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men . Patients were treated with testosterone ( sustanon 200 mg ) or placebo intramuscularly every 2 weeks for 3 months in r and om order followed by a washout period of 1 month before the alternate treatment phase . METHODS Leptin , adiponectin , resistin , tumour necrosis factor-alpha ( TNF-alpha ) , interleukin (IL)-6 and CRP levels were measured before and after each treatment phase . Body mass index ( BMI ) and waist circumference were also recorded . RESULTS At baseline , leptin levels significantly correlated with BMI and waist circumference . There was a significant inverse correlation between baseline IL-6 and total testosterone ( r=-0.68 ; P=0.002 ) and bioavailable testosterone levels ( r=-0.73 ; P=0.007 ) . CRP levels also correlated significantly with total testosterone levels ( r=-0.59 ; P=0.01 ) . Testosterone treatment reduced leptin ( -7141.9 + /- 1461.8 pg/ml ; P=0.0001 ) and adiponectin levels ( -2075.8 + /- 852.3 ng/ml ; P=0.02 ) . There was a significant reduction in waist circumference . No significant effects of testosterone therapy on resistin , TNF-alpha , IL-6 or CRP levels were observed . CONCLUSION Testosterone replacement treatment decreases leptin and adiponectin levels  in type 2 diabetic men . Moreover , low levels of testosterone in men are associated with pro-inflammatory profile , though testosterone treatment over 3 months had no effect on inflammatory markers 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 BACKGROUND The role of testosterone on the development of coronary artery disease in men is controversial . The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone . Conversely , recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men . Accordingly , the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men . METHODS AND RESULTS After withdrawal of antianginal therapy , 14 men ( mean age , 58+/-4 years ) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days ( baseline and either testosterone or placebo given in a r and om order ) . The exercise tests were performed 30 minutes after administration of testosterone ( 2.5 mg IV in 5 minutes ) or placebo . All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo , whereas only 10 patients had a positive exercise test after testosterone .  Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone . Compared with placebo , testosterone increased time to 1-mm ST-segment depression ( 579+/-204 versus 471+/-210 seconds ; P<0 . 01 ) and total exercise time ( 631+/-180 versus 541+/-204 seconds ; P<0 . 01 ) . Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression ( 135+/-12 versus 123+/-14 bpm ; P<0.01 ) and at peak exercise ( 140+/-12 versus 132+/-12 bpm ; P<0.01 ) and the rate-pressure product at the onset of 1-mm ST-segment depression ( 24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm ; P<0.05 ) and at peak exercise ( 26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm ; P<0.05 ) . CONCLUSIONS Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease . This effect may be related to a direct coronary-relaxing effect Introduction : This study investigated the effects of testosterone ( T ) treatment on cognition , mood , and quality of life in men with mild cognitive impairment ( MCI ) and low serum T levels . Methods : A total of 351 community-dwelling men were screened , and 37 men evidence d both MCI and low T of whom 27 agreed for further screening . Twenty-two met all the study inclusion /exclusion criteria and enrolled in a 6-month r and omized , double-blind , placebo-controlled study . Results : Total T levels significantly increased in the T treatment group . No significant changes were observed in measures of cognition , mood , or quality of life other than improvement in 1 objective measure of verbal memory ( P < .05 ) and decreased depression symptoms ( P < .02 ) in the treatment group . Conclusions : Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low Acute administration of high-dose testosterone in men with coronary artery disease improves endothelial function CONTEXT The Heart and Estrogen/progestin Replacement Study ( HERS ) found no overall reduction in risk of coronary heart disease ( CHD ) events among postmenopausal women with CHD . However , in the hormone group , findings did suggest a higher risk of CHD events during the first year , and a decreased risk during years 3 to 5 . OBJECTIVE To determine if the risk reduction observed in the later years of HERS persisted and result ed in an overall reduced risk of CHD events with additional years of follow-up . DESIGN AND SETTING R and omized , blinded , placebo-controlled trial of 4.1 years ' duration ( HERS ) and subsequent unblinded follow-up for 2.7 years ( HERS II ) conducted at outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS ; 2321 women ( 93 % of those surviving ) consented to follow-up in HERS II . INTERVENTION Participants were r and omly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate ( n = 1380 ) , or placebo ( n = 1383 ) during HERS ; open-label hormone therapy was prescribed at personal physicians ' discretion during HERS II . The proportions with at least 80 % adherence to hormones declined from 81 % ( year 1 ) to 45 % ( year 6 ) in the hormone group , and increased from 0 % ( year 1 ) to 8 % ( year 6 ) in the placebo group . MAIN OUTCOME MEASURES The primary outcome was nonfatal myocardial infa rct ion and CHD death . Secondary cardiovascular events were coronary revascularization , hospitalization for unstable angina or congestive heart failure , nonfatal ventricular arrhythmia , sudden death , stroke or transient ischemic attack , and peripheral arterial disease . RESULTS There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS , HERS II , or overall . The unadjusted relative hazard ( RH ) for CHD events in HERS was 0.99 ( 95 % confidence interval [ CI ] , 0.81 - 1.22 ) ; HERS II , 1.00 ( 95 % CI , 0.77 - 1.29 ) ; and overall , 0.99 ( 0.84 - 1.17 ) . The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups ( RH , 0.97 ; 95 % CI , 0.82 - 1.14 ) , and in analyses restricted to women who were adherent to r and omized treatment assignment ( RH , 0.96 ; 95 % CI , 0.77 - 1.19 ) . CONCLUSIONS Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up . After 6.8 years , hormone therapy did not reduce risk of cardiovascular events in women with CHD . Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD How do human beings decide when to be selfish or selfless ? In this study , we gave  testosterone to 25 men to establish its impact on prosocial behaviors  in a double-blind within-subjects design . We also confirmed participants ' testosterone levels before and after treatment through blood draws . Using the Ultimatum Game from behavioral economics , we find that men with artificially raised T , compared to themselves on placebo , were 27 % less generous towards strangers with money they controlled ( 95 % CI placebo : ( 1.70 , 2.72 ) ; 95 % CI T : ( .98 , 2.30 ) ) . This effect scales with a man 's level of total- , free- , and dihydro-testosterone ( DHT ) . Men in the lowest decile of DHT were 560 % more generous than men in the highest decile of DHT . We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them . Our results continue to hold after controlling for altruism . We conclude that elevated testosterone causes men to behave antisocially Testosterone increases fat-free mass ( FFM ) in men infected with human immunodeficiency virus ( HIV ) , but its effects on muscle performance , physical function , mood , and quality of life are poorly understood . Sixty-one HIV-infected men with weight loss were r and omized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk . The primary outcome of interest was physical function ( walking speed , stair-climbing power , and load-carrying ability ) . Secondary outcome measures included body weight and composition , muscle performance , sexual function , mood , and quality of life . Serum nadir free and total testosterone levels increased ( + 188.0 + /- 29.6 and + 720 + /- 86 ng/dl ) in the testosterone , but not placebo , group . Testosterone administration was associated with increased FFM ( 2.8 + /- 0.5 kg ) , which was significantly greater than in the placebo group ( P < 0.0001 ) . Leg press strength increased significantly in testosterone-treated ( P = 0.027 ) , but not placebo-treated , men ; the difference between groups was not significant . Other measures of muscle performance and physical function did not change significantly in either group . Men receiving testosterone demonstrated significantly greater improvements in mental health and quality -of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo .  Sexual function scores did not change in either group . In HIV-infected men with weight loss , a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function . Improvements in mood , fatigue , and quality -of-life measures in the testosterone group , although clinical ly important , need further confirmation The effects of supraphysiological levels of testosterone , used for male contraception , on sexual behavior and mood were studied in a single-blind , placebo-controlled manner in a group of 31 normal men . After 4 weeks of baseline observations , the men were r and omized into two groups : one group received 200 mg testosterone enanthate ( TE ) weekly by i m injection for 8 weeks ( Testosterone Only group ) , the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks ( Placebo/Testosterone group ) . The testosterone administration increased trough plasma testosterone levels by 80 % , compatible with peak testosterone levels 400 - 500 % above baseline . Various aspects of sexuality were assessed using sexuality experience scales ( SES ) question naires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales . In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES ( i.e. SES 2 ) following testosterone administration , but not with placebo . There were no changes in SES 3 , which measures aspects of sexual interaction with the partner . In both groups there were no changes in frequency of sexual intercourse , masturbation , or penile erection on waking nor in any of the moods reported . The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo . The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone . However , these changes are not reflected in modifications of overt sexual behavior , which in eugonadal men may be more determined by sexual relationship factors . This contrasts with hypogonadal men , in whom testosterone replacement clearly stimulates sexual behavior . There was no evidence to suggest an alteration in any of the mood states studied , in particular those associated with increased aggression . We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships . Raising testosterone does not increase self-reported ratings of aggressive feelings Hypogonadism is prevalent among human immunodeficiency virus-infected men , in whom significantly reduced quality of life and mood disturbances have been reported . Previous studies have not investigated the relationship between depression score and gonadal function among such patients . We first compared depression scores in  hypogonadal ( n = 52 ) and eugonadal ( n = 10 ) patients with acquired immunodeficiency syndrome ( AIDS ) wasting , matched for weight and disease status , and then investigated the effects of testosterone administration on depression score in a r and omized , double-blind , placebo-controlled study among the group of hypogonadal men with AIDS wasting . The primary end point in all comparisons was the Beck Depression Inventory .  Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal- , age- , weight- , and disease status-matched subjects ( 15.5+/-1.1 vs. 10.6+/-1.4 mean + /- SEM , P = 0.02 ) . Among the combined hypogonadal and eugonadal subjects , a significant inverse correlation was seen between the Beck score and both free ( r = 0.41 , P<0.01 ) and total serum testosterone levels ( r = -0.43 , P<0.001 ) . The relationship between the Beck score and testosterone levels remained highly significant , controlling for weight , viral load , CD4 count , and antidepressant use ( P<0.01 for free testosterone , P<0.001 for total testosterone ) . Furthermore , when subjects were divided into two groups , based on a Beck score greater than 18 or less than or equal to 18 , serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18 , whereas there were no differences in weight , viral load , CD4 count , or Karnofsky status . End of study data were available in 39 patients who completed the r and omized , placebo-controlled study . Beck score decreased significantly only in the subjects receiving testosterone ( -5.8+/-1.3 , P < 0.001 ) , but not in subjects r and omized to placebo ( -2.7+/-1.3 , P > 0.05 ) . In a regression analysis , the change in Beck score was related significantly to change in weight ( P<0.01 ) . These data demonstrate increased depression score in association with hypogonadism in men with AIDS wasting , independent of weight , virologic status , and other disease factors . In such patients , administration of testosterone results in a significant improvement in depression inventory score . This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and /or other anthropometric indices . Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients BACKGROUND Field studies of illicit anabolic- and rogenic steroid users suggest that some develop manic or aggressive reactions to these drugs-a potential public health problem . However , controlled laboratory evaluations of these effects remain limited . METHODS In a r and omized , placebo-controlled , crossover trial , we administered testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and placebo for 6 weeks , separated by 6 weeks of no treatment , to 56 men aged 20 to 50 years .  Psychiatric outcome measures included the Young Mania Rating Scale ( YMRS ) , the Point Subtraction Aggression Paradigm ( a computerized provocation test of aggression ) , the Aggression Question naire of Buss and Perry , the Symptom Checklist-90-R , daily diaries of manic and depressive symptoms , and similar weekly diaries completed by a " significant other " who knew the participant well . RESULTS Testosterone treatment significantly increased manic scores on the YMRS ( P = .002 ) , manic scores on daily diaries ( P = .003 ) , visual analog ratings of liking the drug effect ( P = .008 ) , and aggressive responses on the Point Subtraction Aggression Paradigm ( P = .03 ) . Drug response was highly variable : of 50 participants who received 600 mg/wk of testosterone cypionate , 42 ( 84 % ) exhibited minimal psychiatric effects ( maximum YMRS score , < 10 ) , 6 ( 12 % ) became mildly hypomanic ( YMRS score , 10 - 19 ) , and 2 ( 4 % ) became markedly hypomanic ( YMRS score , > or = 20 ) . The 8 " responders " and 42 " nonresponders " did not differ significantly on baseline demographic , psychological , laboratory , or physiological measures . CONCLUSIONS Testosterone administration , 600 mg/wk increased ratings of manic symptoms in normal men . This effect , however , was not uniform across individuals ; most showed little psychological change , whereas a few developed prominent effects . The mechanism of these variable reactions remains unclear Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer .  Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) < 70 ng/dL and fatigue score > 3/10 on the Edmonton Symptom Assessment Scale were eligible .  Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted 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 Transbuccal administration of drugs provides an easy route of administration . To test the safety and efficacy of a novel testosterone ( T ) product , we performed a r and omized , double blind , placebo-controlled study in a parallel design . Men with serum T levels below 250 ng/dL were administered either an active buccal tablet containing 10 mg T ( n = 7 ) or a buccal placebo tablet ( n = 6 ) containing 3 mg pseudoephedrine HCl for taste matching . Men were studied while taking a st and ard T enanthate dose , after 6 weeks of a wash-out period , and after 8 weeks of therapy . The men were matched for age ( mean + /- SD , 41 + /- 16 vs. 47 + /- 16 ) and type of hypogonadism ( three primary testicular failures in each group , with the remainder having a central etiology ) . Acute pharmacokinetic testing showed peak serum hormone levels at 30 min , with a mean serum T concentration of 2688 + /- 147 ng/dL ( range , 1820 - 3770 ng/dL ) . Levels returned to baseline in 4 - 6 h , result ing in a total T area under the curve level of 3865 ng/hn.dL , less than that using other available forms of T administration . Similar pharmacokinetics were observed for the hormone 's metabolites , bioavailable T , free T , and estradiol . After 8 weeks of treatment , the results of nocturnal penile tumescence studies evaluating rigidity and circumference were significantly different from those in the placebo group ( P < 0.05 ) and comparable to those during T enanthate therapy . In conclusion , transbuccal T therapy was sufficient to maintain normal sexual function while minimizing the total time of exposure to elevated circulating serum T levels 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 OBJECTIVES The effect of testosterone ( T ) on sexual function in men is well established . However , less is known about its effects on cognitive function . The aim of this study is to investigate the relationship between T levels and sex-typed cognitive abilities in both eugonadal and hypogonadal men . DESIGN A single-blind placebo-controlled design was employed in this study . METHODS Thirty healthy eugonadal men and seven hypogonadal men participated in the study . Eugonadal men were r and omised into one of two treatment regimens : ( 1 ) active group -- receiving 200 mg of T enanthate i.m . weekly for 8 weeks ( raising T levels into the supraphysiological range ) or ( 2 ) placebo group -- receiving 200 mg of sodium chloride i.m . weekly for 8 weeks . The hypogonadal group received the physiological replacement dose of 200 mg T enanthate i.m . bi-weekly for 8 weeks . All groups underwent a battery of neuropsychological tests and had circulating T measured at baseline , and at weeks 4 and 8 during treatment . RESULTS A significant time by group interaction effect was found in the measure of spatial ability ( i.e. , block design test ) indicating that the active group 's performance declined significantly at week 4 , compared to placebo group ( F(4,64)=3.78 , P<0.01 ) . Conversely , the active group performed significantly better than the placebo group in the measure of verbal fluency ( i.e. , the Controlled Oral Word Association Test ) at week 4 ( F(4,64)=2.54 , P<0.05 ) . No significant changes were found on any of the other tests . Generally , the hypogonadal group performed less well than the eugonadal groups on all tests . CONCLUSIONS These results offer support to the notion that increased T has a differential effect on cognitive function , inhibiting spatial abilities while improving verbal fluency in eugonadal men Objective : To determine the efficacy of testosterone ( T ) supplementation on cognition in a sample of men with Alzheimer disease ( AD ) or mild cognitive impairment ( MCI ) . Methods : Fifteen patients with AD and 17 patients with MCI aged 63 to 85 years completed a r and omized , double-blind , placebo-controlled study . Nineteen participants received weekly intramuscular ( IM ) injections of 100 mg T enanthate and 13 participants received weekly injections of placebo ( saline ) for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , week 3 , and week 6 of treatment and again after 6 weeks of washout . Results : Peak serum total T levels were raised from baseline an average of 295 % in the active treatment group . Improvements in spatial memory ( p < 0.05 ) and constructional abilities ( p < 0.05 ) and verbal memory were evident in the T group . No changes were noted for selective and divided attention or language . Prostate specific antigen did not significantly change during this brief treatment . Conclusion : Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment 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 The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels . Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors . Tau protein deposition is also affected by and rogen supplementation in animals . We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition , in particular the visual-spatial domain . Thirty-six male patients with a new diagnosis of Alzheimer 's disease had their total and bioavailable testosterone levels measured . None of the patients had been on acetylcholinesterase inhibitors .  Ten of the 36 patients ( 28 % ) were deemed biochemically hypogonadal ( total testosterone < 240 ng/dl or 7 nmol/l ) . Five of the hypogonadal patients were r and omized to testosterone and five to placebo . Initial Alzheimer 's Disease Assessment Scale cognitive subscale ( ADAScog ) and Mini Mental Status Examination ( MMSE ) ranged from 31 to 19 and from 17 to 22 , respectively . The  clock drawing test ( CDT ) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities . Normal prostate-specific antigen ( PSA ) levels were essential before treatment with intramuscular testosterone , 200 mg every 2 weeks . Measurement of testosterone , complete blood count , lipids , PSA and neuropsychological cognitive tests were repeated at 3 , 6 , 9 and 12 months of treatment . In the testosterone-treated group , levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l ( p = 0.11 ) . Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l ( p = 0.10 ) . PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml ( p = 0.07 ) . ADAScog improved from a mean of 25 to 16.3 ( p = 0.02 ) ; MMSE improved from a mean of 19.4 to 23.2 ( p = 0.02 ) , CDT also improved from 2.2 to 3.2 ( p = 0.07 ) . One patient stopped treatment because of hypersexual behavior . The placebo-treated group deteriorated gradually . This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition , including visual-spatial skills in mild to moderate Alzheimer 's disease A r and omised double blind study was carried out with 50 men who had ST segment depression of 0.1 mV or more after a modified two-step exercise test . Rate and duration of exercise were the same for the last of each subject 's several pretreatment tests as for his tests after 4 and 8 weeks of treatment with placebo or testosterone cypionate , 200 mg , intramuscularly weekly . The sum of ST segment depression in leads II , V4 , V5 , and V6 taken immediately , and 2 , 4 , and 6 minutes after exercise did not change significantly after 4 or 8 weeks of placebo treatment , but did decrease by 32 per cent ( P less than 0.0001 ) and 51 per cent ( P less than 0.0001 ) after 4 and 8 weeks , respectively , of testosterone cypionate treatment . The mechanism by which testosterone cypionate treatment results in lessened postexercise ST segment depression is not established In the last ten years , numerous mechanisms by which sex steroids modify cortical function have been described . For example , estrogen replacement improves verbal memory in women , and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function . Little is known about sex steroid effects on other aspects of memory , such as frontal lobe-mediated working memory . We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women . Before hormone supplementation , working memory , tested with the Subject Ordered Pointing Test ( SOP ) , was worse in older subjects than younger subjects , and there was no evidence of gender differences at either age . Testosterone supplementation  improved working memory in older men , but a similar enhancement of working memory was not found in older women supplemented with estrogen . In men , testosterone and estrogen effects were reciprocalwith better working memory related to a higher testosterone to estrogen ratio . These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life 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 CONTEXT Recent clinical trials of i m testosterone in eugonadal men suggest positive effects on verbal memory , but other studies find no effect . OBJECTIVE Our objective was to determine whether supraphysiological testosterone influences verbal memory and brain function during a verbal memory task in healthy eugonadal older men . PATIENTS , DESIGN , AND SETTING Fifteen cognitively normal men , aged 66 - 86 yr , participated in a r and omized , double-blind , placebo-controlled crossover trial involving 9 months of participation per participant at a hospital-based research facility . INTERVENTION We used testosterone enanthate ( 200 mg i m every other week for 90 d ) crossed over with placebo ( sesame oil vehicle i m ) with a 90-d washout between treatments . MAIN OUTCOME MEASURES Performance was assessed on a st and ardized verbal memory test , and brain activity ( relative glucose metabolic rates ) in medial temporal and frontal regions was measured with positron emission tomography during a verbal memory task . RESULTS Treatment increased total testosterone by 241 % . Behavioral results showed a significant decrease in short-delay verbal memory with treatment ( P < 0.05 , effect size = 0.59 sd ) and a nonsignificant decrease on a composite verbal memory measure ( P = 0.09 , effect size = 0.48 sd ) . Positron emission tomography scans revealed decreased relative activity in ventromedial temporal cortex ( i.e. right amygdala/entorhinal cortex ) and increased relative activity in bilateral prefrontal cortex with treatment . CONCLUSIONS Decreased verbal memory and altered relative activity in medial temporal and prefrontal regions suggest possible detrimental effects of supraphysiological testosterone supplementation in elderly men . The results do not rule out potential benefits with other regimens , cognitive tests , or population 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 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 BACKGROUND Our laboratory has previously reported that testosterone ( T ) administration to older men significantly improves cognitive function . This study examined potential changes in insulin-like growth factor ( IGF ) IGF-I , IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning . METHODS Twenty-five healthy community dwelling volunteers , ranging in age from 50 - 80 years were r and omized to receive weekly intra-muscular ( i.m . ) injections of either 100 mg T enanthate or placebo ( saline ) for 6 weeks . Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment . RESULTS Significant positive associations between IGF-I and IGF-II and spatial memory , spatial reasoning , and verbal fluency were observed after 6 weeks of T administration . Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance , whereas estradiol was associated with a decline in divided attention performance . Serum IGF-I , IGF-II and IGFBPs did not change in response to T treatment . CONCLUSIONS Our results suggest that T , estradiol and IGF-I may have independent and selective effects on cognitive functioning . Positive associations between T levels and cognition are consistent with an effect of and rogen treatment , whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition 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 Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease . The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown . OBJECTIVE The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity . METHODS IN this multicenter , r and omized , placebo-controlled , double-blind trial , 88 HIV-positive men with abdominal obesity ( waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm ) and total testosterone 125 - 400 ng/dl , or bioavailable testosterone less than 115 ng/dl , or free testosterone less than 50 pg/ml on stable antiretroviral regimen , and HIV RNA less than 10,000 copies per milliliter were r and omized to receive 10 g testosterone gel or placebo daily for 24 wk . Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0 , 12 , and 24 . We used an intention-to-treat approach and nonparametric statistical methods . RESULTS Baseline characteristics were balanced between groups . In 75 subjects evaluated , median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups ( testosterone 0.3 % , placebo 3.1 % , P = 0.75 ) . Total  ( testosterone -1.5 % , placebo 4.3 % , P = 0.04 ) and sc  ( testosterone-7.2 % , placebo 8.1 % , P < 0.001 ) abdominal fat mass decreased in testosterone-treated men , but increased in placebo group . Testosterone therapy was associated with significant decrease in whole body , trunk , and appendicular fat mass by dual energy x-ray absorptiometry ( all P < 0.001 ) , whereas whole body and trunk fat increased significantly in the placebo group . The percent of individuals reporting a decrease in abdomen ( P = 0.01 ) , neck ( P = 0.08 ) , and breast size ( P = 0.01 ) at wk 24 was significantly greater in testosterone-treated than placebo-treated men . Testosterone-treated men had greater increase in lean body mass than placebo ( testosterone 1.3 % , placebo -0.3 , P = 0.02 ) . Plasma insulin , fasting glucose , and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly . Testosterone therapy was well tolerated . CONCLUSIONS Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body , total , and sc abdominal fat mass and a greater increase in lean mass compared to placebo . However , changes in visceral fat mass were not significantly different between groups . Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk 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 BACKGROUND The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood . One hypothesis is that testosterone enhances spatial abilities , while it might impair verbal skills . METHODS Thirty elderly men received a single testosterone ( 250 mg testosterone enanthate ) or placebo injection .  Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests . RESULTS Five days after injection , testosterone and estradiol levels were still in the supraphysiologic range . In the verbal fluency task , the placebo group , but not the testosterone group , showed a practice effect . Therefore , the testosterone group performed significantly worse than the placebo group after treatment . No effects of testosterone were observed in the other verbal and spatial tasks . CONCLUSIONS The present finding , that testosterone blocks the practice effect in verbal fluency , partly supports the general idea that sex steroids modulate performance in tests with known gender differences . Moreover it demonstrates that these effects can occur rapidly . However , beneficial effects on spatial cognition or memory might need more time to develop and /or might only occur when a less pronounced testosterone increase is induced Testosterone ( T ) levels decline as men age , but it is unclear whether this has an effect on cognition . Some studies indicate that lower T levels are associated with memory loss ; thus , maintaining a higher T level could have positive effects on aspects of cognitive function . Concerns exist , however , about the effect of T therapy on the prostate in older men . We hypothesized that T replacement in older men with low T levels would improve aspects of cognitive function and that the addition of finasteride would not affect the T-induced cognitive improvements .  Healthy men , 65 to 83 years of age , with baseline total T below 350 ng/dL and no evidence of cognitive impairment were r and omly assigned to 1 of 3 regimens : 200 mg of T every 2 weeks by intramuscular injection with placebo pill daily ( T-only ) , 200 mg of T every 2 weeks by intramuscular injection with 5 mg of finasteride daily ( T+F ) , or placebo injections and pills ( placebo ) . Sixty-nine men completed baseline cognitive testing ; 65 completed at least 4 months , and 46 completed all 36 months of the study . Participants were given a battery of cognitive evaluations at baseline , 4 months , and 36 months , along with measurement of serum hormone levels . Serum total T , bioavailable T , and estradiol levels in the T-only and T+F groups significantly increased throughout the treatment period , whereas these hormone levels did not change in the placebo group . Only minimally significant differences were seen among the 3 groups in any evaluation of cognitive performance , either in the short-term ( 4 months ) or the long-term ( 36 months ) analysis . These results indicate that T replacement , whether given alone or in combination with finasteride , for 36 months in healthy older men without cognitive impairment at baseline has no clinical ly significant effect on tests of cognitive function . Further studies are warranted to determine whether hormone replacement in men with preexisting cognitive impairment is beneficial IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown . A recent r and omized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety . OBJECTIVES To assess the association between testosterone therapy and all-cause mortality , myocardial infa rct ion ( MI ) , or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease . DESIGN , SETTING , AND PATIENTS A retrospective national cohort study of men with low testosterone levels ( < 300 ng/dL ) who underwent coronary angiography in the Veterans Affairs ( VA ) system between 2005 and 2011 . MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality , MI , and ischemic stroke . RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL , 1223 patients started testosterone therapy after a median of 531 days following coronary angiography . Of the 1710 outcome events , 748 men died , 443 had MIs , and 519 had strokes . Of 7486 patients not receiving testosterone therapy  , 681 died , 420 had MIs , and 486 had strokes . Among 1223 patients receiving testosterone therapy , 67 died , 23 had MIs , and 33 had strokes . At 3 years after coronary angiography , the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group , with an absolute risk difference of 5.8%(95%CI , -1.4%to 13.1 % ) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1 % vs 11.3 % ; at 2 years , 15.4 % vs 18.5 % ; and at 3 years , 19.9 % vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease ( test for interaction , P = .41 ) . CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level , the use of testosterone therapy was associated with increased risk of adverse outcomes . These findings may inform the discussion about the potential risks of testosterone therapy OBJECTIVE In women , sex hormones cause increased morbidity and mortality in patients with coronary heart disease ( CHD ) and adversely affect the coagulation profile . We have studied the effect of physiological testosterone replacement therapy in men on coagulation factor expression , to determine if there is an increased risk of thrombosis . METHODS Double-blind , r and omized , placebo-controlled trial of testosterone in 46 men with chronic stable angina . Measurements of free , total and bioavailable testosterone , luteinising hormone ( LH ) and follicle-stimulating hormone ( FSH ) , estradiol , plasminogen activator inhibitor-1 ( PAI-1 ) , fibrinogen , tissue plasminogen activator ( tPA ) and full blood count were made at 0 , 6 and 14 weeks . RESULTS Bioavailable testosterone levels were : 2.58 + /- 0.58 nmol/l at baseline , compared with 3.35 + /- 0.31 nmol/l at week 14 ( P < 0.001 ) after treatment compared with 2.6 + /- 0.18 nmol/l and 2.44 + /- 0.18 nmol/l in the placebo group ( P was not significant ) . There was no change in fibrinogen ( 3.03 + /- 0.18 g/l at baseline and 3.02 + /- 0.18 g/l at week 14 , P = 0.24 ) , tPA activity ( 26.77 + /- 4.9 Iu/ml and 25.67 + /- 4.4 Iu/ml , P = 0.88 ) or PAI-1 activity ( 0.49 + /- 0.85 Iu/ml and 0.36 + /- 0.06 Iu/ml , P = 0.16 ) with active treatment and no differences between the groups ( at week 14 , P value 0.98 , 0.59 and 0.8 for fibrinogen , PAI-1 and tPA respectively ) . Haemoglobin concentration did not change over time , in the testosterone group ( 1.44 + /- 0.02 g/l and 1.45 + /- 0.02 g/l , P = 0.22 ) . CONCLUSION Physiological testosterone replacement does not adversely affect blood coagulation status 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 . 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 OBJECTIVE Low levels of testosterone in men have been shown to be associated with type 2 diabetes , visceral adiposity , dyslipidaemia and metabolic syndrome . We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes . DESIGN This was a double-blind placebo-controlled crossover study in 24 hypogonadal men ( 10 treated with insulin ) over the age of 30 years with type 2 diabetes . METHODS Patients were treated with i.m . testosterone 200 mg every 2 weeks or placebo for 3 months in r and om order , followed by a washout period of 1 month before the alternate treatment phase . The primary outcomes were changes in fasting insulin sensitivity ( as measured by homeostatic model index ( HOMA ) in those not on insulin ) , fasting blood glucose and glycated haemoglobin . The secondary outcomes were changes in body composition , fasting lipids and blood pressure . Statistical analysis was performed on the delta values , with the treatment effect of placebo compared against the treatment effect of testosterone . RESULTS Testosterone therapy reduced the HOMA index ( -1.73 + /- 0.67 , P = 0.02 , n = 14 ) , indicating an improved fasting insulin sensitivity . Glycated haemoglobin was also reduced ( -0.37 + /- 0.17 % , P = 0.03 ) , as was the fasting blood glucose ( -1.58 + /- 0.68 mmol/l , P = 0.03 ) . Testosterone treatment result ed in a reduction in visceral adiposity as assessed by waist circumference ( -1.63 + /- 0.71 cm , P = 0.03 ) and waist/hip ratio ( -0.03 + /- 0.01 , P = 0.01 ) . Total cholesterol decreased with testosterone therapy ( -0.4 + /- 0.17 mmol/l , P = 0.03 ) but no effect on blood pressure was observed . CONCLUSIONS Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes . Improvements in glycaemic control , insulin resistance , cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk Abstract Purpose : We aim ed to compare therapeutic effects of intramuscular ( IM ) n and rolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome ( AWS ) with placebo control . Methods : In this r and omized , double-blind , placebo-controlled , 12-week trial , 104 patients with AWS who satisfied our inclusion criteria were r and omly allotted in a 2:2:1 ratio to the 3 intervention groups : n and rolone , testosterone , and placebo . We administered 150 mg n and rolone and 250 mg testosterone ( both IM , biweekly ) . The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the n and rolone decanoate , testosterone , and placebo groups . Results : Intent-to-treat analysis was done . The n and rolone group recorded maximum mean increase in weight ( 3.20 kg ; post hoc P < .01 compared to placebo ) . Body mass index ( BMI ) of subjects in the n and rolone group had a significantly greater increase ( mean = 1.28 ) compared to both testosterone ( post hoc P < .05 ) and placebo ( post hoc P < .01 ) . Waist circumference and triceps skinfold thickness of patients on n and rolone showed similar results . N and rolone also ensured a better quality of life . Patients with low testosterone level ( <3 ng/mL ) benefited immensely from n and rolone therapy , which increased their weight and BMI significantly compared to placebo ( P < .05 ) . Conclusion : Our trial demonstrates the superior therapeutic effects of n and rolone in male AWS patients , including the and rogen deficient BACKGROUND The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms ( diminished libido , depressed mood , low energy , and depleted muscle mass ) in men with symptomatic human immunodeficiency virus illness . METHODS Seventy-four patients were enrolled in a double-blind , placebo-controlled 6-week trial with bi-weekly testosterone injections , followed by 12 weeks of open-label maintenance treatment . Major outcome measures were Clinical Global Impressions Scale ratings for libido , mood , energy , and erectile function ; Hamilton Depression Rating Scale scores , and Chalder Fatigue Scale scores . Body composition changes were assessed with bioelectric impedance analysis . RESULTS Seventy men completed the 6-week trial . Response rates , defined as much or very much improved libido , were 74 % ( 28/38 ) for patients r and omized to testosterone , and 19 % ( 6/32 ) for placebo-treated patients ( P<.001 ) . Of the 62 completers with fatigue at baseline , 59 % ( 20/34 ) receiving testosterone and 25 % ( 7/28 ) receiving placebo reported improved energy ( P<.01 ) . Among the 26 completers with an Axis I depressive disorder at baseline , 58 % of the testosterone-treated patients reported improved mood compared with 14 % of placebo-treated patients ( Fisher exact test = .08 ) . With testosterone treatment , average increase in muscle mass over 12 weeks was 1.6 kg for the whole group , and 2.2 kg for the 14 men with wasting at baseline . Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks . CONCLUSION Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness , restoring libido and energy , alleviating depressed mood , and increasing muscle mass CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD 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 To To compare testosterone undecanoate versus propionyl-L-carnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms . METHODS A total of 120 patients were r and omized into three groups . The mean patient age was 66 years ( range 60 to 74 ) . Group 1 was given testosterone undecanoate 160 mg/day , the second group was given propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day . The third group was given a placebo ( starch ) . Drugs and placebo were given for 6 months . The assessed variables were total prostate-specific antigen , prostate volume , peak systolic velocity , end-diastolic velocity , resistive index of cavernosal penile arteries , nocturnal penile tumescence , total and free testosterone , prolactin , luteinizing hormone , International Index of Erectile Function score , Depression Melancholia Scale score , fatigue scale score , and incidence of side effects . The assessment was performed at intervals before , during , and after therapy . RESULTS Testosterone and carnitines significantly improved the peak systolic velocity , end-diastolic velocity , resistive index , nocturnal penile tumescence , International Index of Erectile Function score , Depression Melancholia Scale score , and fatigue scale score . Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score . Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone ; carnitines did not . No drug significantly modified prostate-specific antigen or prolactin . Carnitines and testosterone proved effective for as long as they were administered , with suspension provoking a reversal to baseline values . Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension . Placebo administration proved ineffective . Negligible side effects emerged . CONCLUSIONS Testosterone and , especially , carnitines proved to be active drugs for the therapy of symptoms associated with male aging objectives We have recently shown that , in men with erectile dysfunction ( ED ) , free testosterone ( FT ) directly correlates with penile arterial inflow . This led us to further investigate the effect(s ) of and rogen administration on cavernous arteries in patients failing sildenafil treatment CONTEXT Declines in GH and testosterone ( Te ) secretion may contribute to the detrimental aging changes of elderly men . OBJECTIVE To assess the effects of near-physiological GH with/without Te administration on lean body mass , total body fat , midthigh muscle cross-section area , muscle strength , aerobic capacity , condition-specific quality of life ( Age-Related Hormone Deficiency-Dependent Quality of Life question naire ) , and generic health status ( 36-Item Short-Form Health Survey ) of older men . DESIGN , SETTING S , AND PARTICIPANTS A 6-month , r and omized , double-blind , placebo-controlled trial was performed on 80 healthy , community-dwelling , older men ( age , 65 - 80 yr ) . INTERVENTIONS Participants were r and omized to receive 1 ) placebo GH or placebo Te , 2 ) recombinant human GH ( rhGH ) and placebo Te ( GH ) , 3 ) Te and placebo rhGH ( Te ) , or 4 ) rhGH and Te ( GHTe ) . GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range . A fixed dose of Te ( 5 mg ) was given by transdermal patches . RESULTS Lean body mass increased with GHTe ( P = 0.008 ) and GH ( P = 0.004 ) , compared with placebo . Total body fat decreased with GHTe only ( P = 0.02 ) . Midthigh muscle ( P = 0.006 ) and aerobic capacity ( P < 0.001 ) increased only after GHTe . Muscle strength changes were variable ; one of six measures significantly increased with GHTe . Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life question naire score ( P = 0.007 ) in the GH and GHTe groups . Bodily pain increased with GH alone , as determined by the Short-Form Health Survey ( P = 0.003 ) . There were no major adverse effects . CONCLUSION Coadministration of low dose GH with Te result ed in beneficial changes being observed more often than with either GH or Te alone Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function . We have conducted a double-blind , r and omized , placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level < 13.7 nmol l−1 . Participants were r and omly assigned to receive oral testosterone undecanoate or a placebo for 6 months . A total of 207 men completed the study . After treatment , there were no differences in scores on sexual function between the groups . Sub analysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies , desire of sexual contact and frequency of sexual contact , supplementation of testosterone did not result in improvement on any of these items in this group . In conclusion , the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function OBJECTIVE Hypogonadism and subthreshold depression are common conditions in elderly men . The objective of this study was to examine the effect of testosterone treatment in older , hypogonadal men with subthreshold depression . METHOD A r and omized , double-blind , placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older ( N = 33 ) with screening total testosterone levels of < or= 280 ng/dL and subthreshold depression ( dysthymia or minor depression , according to DSM-IV ) . Recruitment for the study was conducted from November 2002 through May 2005 . Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks , followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel . The primary outcome measure was the change in the Hamilton Rating Scale for Depression ( HAM-D ) score from baseline to the end of the double-blind phase . Secondary outcome measures were remission of subthreshold depression ( defined a priori as a HAM-D score < or= 7 ) and changes in the Hopkins Symptom Checklist depression scale , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the short-form 16-item Quality of Life Enjoyment and Satisfaction Question naire . RESULTS At the end of the double-blind phase , testosterone-treated men had a greater reduction in HAM-D scores ( p = .024 ) and a higher remission rate of subthreshold depression ( 52.9 % vs. 18.8 % , p = .041 ) than did placebo-treated men , but there were no differences in other secondary outcome measures between groups . At the end of the open-label phase , the testosterone group had sustained improvement , the control group improved , and there were no differences between groups in any outcome measures . CONCLUSION These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism . Larger studies are needed to corroborate these findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00202462 BACKGROUND Symptoms of male hypogonadism include low libido , fatigue , and dysphoria and are alleviated with testosterone replacement . The prevalence of major depressive disorder ( MDD ) in hypogonadal men is not known , nor is the antidepressant efficacy of testosterone replacement in depressed , hypogonadal men . METHOD A 6-week double-blind , placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level , defined as total serum testosterone < or = 350 ng/dL. Patients were r and omly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate , 200 mg , or sesame seed oil ( placebo ) . The primary outcome measure was the 24-item Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Thirty patients were r and omly assigned to an intervention ; 13 received testosterone , and 17 received placebo .  Mean + /- SD age was 52+/-10 years , mean testosterone level was 266.1+/-50.6 ng/dL , and mean baseline HAM-D score was 21+/-8 . All patients who received testosterone achieved normalization of their testosterone levels . The HAM-D scores decreased in both testosterone and placebo groups , and there were no significant between-group differences : reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo .  Response rate , defined as a 50 % or greater reduction in HAM-D score , was 38.5 % ( 5/13 ) for patients who received testosterone and 41.2 % ( 7/17 ) for patients who received placebo . Patients receiving testosterone had a marginal but statistically significant improvement in sexual function ( p = .02 ) . CONCLUSION In this clinical trial with depressed , hypogonadal men , antidepressant effects of testosterone replacement could not be differentiated from those of placebo 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 Testosterone plays a role in the organization of behavior during development . The authors examined whether testosterone could play a maintenance role in behavior as well . In a double-blind manner , verbal and visual memory , spatial cognition , motor speed , cognitive flexibility , and mood in a group of healthy older men who were supplemented for 3 months with testosterone  were assessed . The increase in testosterone levels to 150 % of baseline levels result ed in a significant enhancement of spatial cognition , but no change in any other cognitive domain was found . Testosterone supplementation influenced the endogenous production of estradiol , and estradiol was found to have an inverse relationship to spatial cognitive performance . These results suggest that testosterone supplementation can modify spatial cognition in older men ; however , it is likely that this occurs through testosterone 's influence on estrogen 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 To investigate ( 1 ) the effects of exogenous testosterone ( T ) on  self- and partner-reported aggression and mood  and ( 2 ) the role of trait impulsivity in the T-aggression relationship .  Thirty eugonadal men with partners were r and omized into two treatment groups to receive : ( 1 ) 200 mg i m T enanthate weekly for 8 weeks or ( 2 ) 200 mg i m sodium chloride weekly for 8 weeks . Eight hypogonadal men received 200 mg i m T enanthate biweekly for 8 weeks . All groups completed a battery of behavior measures at baseline ( Week 0 ) and at Weeks 4 and 8 . Cognitive and motor impulsivity were the only predictors of self-reported total aggression ( over and above age and T levels ) at Weeks 0 , 4 , and 8 . No significant changes in aggression or mood levels were found in the eugonadal-treated group . Significant reductions in negative mood ( tension , anger , and fatigue ) followed by an increase in vigor were found in response to T treatment in the hypogonadal group . These results demonstrate that inability to control one 's behavior when such control is required by a particular situation ( impulsivity ) was found to significantly predict levels of aggression over and above age and T level . These data do not support the hypothesis that supraphysiological levels of T ( within this range ) lead to an increase in self- and partner-reported aggression or mood disturbances . Instead , for the first time , this study has identified the high level of negative affect experienced by hypogonadal patients . These findings have implication s for T replacement therapy and male contraception UNLABELLED Anecdotal reports of " roid rage " and violent crimes by and rogenic steroid users have brought attention to the relationship between anabolic steroid use and angry outbursts . However , testosterone effects on human aggression remain controversial . Previous studies have been criticized because of the low and rogen doses , lack of placebo control or blinding , and inclusion of competitive athletes and those with preexisting psychopathology . To overcome these pitfalls , we used a double-blind , placebo-controlled design , excluded competitive athletes and those with psychiatric disorders , and used 600 mg testosterone enanthate (TE)/week . Forty-three eugonadal men , 19 - 40 yr , were r and omized to 1 of 4 groups : Group I , placebo , no exercise ; Group II , TE , no exercise ; Group III , placebo , exercise ; Group IV , TE plus exercise . Exercise consisted of thrice weekly strength training sessions . The Multi-Dimensional Anger Inventory ( MAI ) , which includes 5 different dimensions of anger ( inward anger , outward anger , anger arousal , hostile outlook , and anger eliciting situations ) , and a Mood Inventory ( MI ) , which includes items related to mood and behavior , were administered to subjects before , during , and after the 10 week intervention . The subject 's significant other ( spouse , live-in partner , or parent ) also answered the same questions about the subject 's mood and behavior ( Observer Mood Inventory , OMI ) . No differences were observed between exercising and nonexercising and between placebo and TE treated subjects for any of the 5 subdomains of MAI . Overall there were no significant changes in MI or OMI during the treatment period in any group . CONCLUSION Supraphysiological doses of testosterone , when administered to normal men in a controlled setting , do not increase angry behavior . These data do not exclude the possibility that still higher doses of multiple steroids might provoke angry behavior in men with preexisting psychopathology The present study assessed the effects of supraphysiologic doses of testosterone on  aggressive responding  in a controlled laboratory setting . Eight male subjects received gradually increasing doses of testosterone cypionate ( 150 mg/week for two weeks , 300 mg/week for two weeks , and 600 mg/week for two weeks ) or placebo using a double-blind , r and omized , cross-over design . Subjects were tested both before and after the series of injections . During the experimental session subjects could press a button to accumulate points exchangeable for money ( non-aggressive response ) or press another button to subtract points from a fictitious opponent ( aggressive response ) . Aggressive responding was instigated by subtracting points from the subject which was attributable to the fictitious opponent . Testosterone administration result ed in a significantly higher number of aggressive responding compared to placebo INTRODUCTION In short-term studies , testosterone replacement therapy has been shown to protect male subjects from exercise-induced ischaemia and modify cardiovascular risk factors such as insulin resistance , fat mass and lipid profiles . METHODS This r and omised parallel group controlled trial was design ed to assess the treatment effect of testosterone therapy ( Nebido ) compared with placebo in terms of exercise-induced ischaemia , lipid profiles , carotid intima-media thickness ( CIMT ) and body composition during 12 months treatment in men with low testosterone levels and angina . RESULTS A total of 15 men were recruited but 13 ( n=13 ) reached adequate duration of follow-up ; seven were treated with testosterone  and six with placebo . Testosterone increased time to ischaemia ( 129+/-48 s versus 12+/-18 , P=0.02 ) and haemoglobin ( 0.4+/-0.6 g/dl versus -0.03+/-0.5 , P=0.04 ) , and reduced body mass index ( -0.3 kg/m(2 ) versus 1.3+/-1 , P=0.04 ) and triglycerides ( -0.36+/-0.4 mmol/l versus 0.3+/-1.2 , P=0.05 ) . The CIMT decreased in the testosterone group more than placebo , but full between group analyses suggested this was only a statistical trend ( -0.5+/-0.1 vs -0.09+/-0.06 , P=0.16 ) . There were no significant effects on serum prostate specific antigen , total or high-density lipoprotein cholesterol ; or on mood and symptom scores as assessed by Seattle Angina Score and EuroQol . CONCLUSION The protective effect of testosterone on myocardial ischaemia is maintained throughout treatment without decrement . Previously noted potentially beneficial effects of testosterone on body composition were confirmed and there were no adverse effects Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome ( AIDS ) wasting syndrome ( AWS ) .  Testosterone and exercise increase muscle mass in men with AWS , with unclear effects on muscle composition . We examined muscle composition in 54 eugonadal men with AWS who were r and omized to 1 ) testosterone ( 200 mg i m weekly ) or placebo and simultaneously to 2 ) resistance training or no training in a 2 x 2 factorial design . At baseline and after 12 wk , we performed assessment s of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition . Leaner muscle has greater attenuation . Baseline muscle attenuation correlated inversely with whole body fat mass ( r = -0.52 , P = 0.0001 ) . This relationship persisted in a model including age , body mass index , testosterone level , viral load , lean body mass , and thigh muscle cross-sectional area ( P = 0.02 ) . Testosterone ( P = 0.03 ) and training ( P = 0.03 ) increased muscle attenuation . These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training . Anabolic therapy in these patients increases muscle leanness Background : Treatment-resistant depression is a persistent clinical problem . Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement , although this strategy has received limited systematic study . Objective : The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression . Method : Twenty-six healthy adult men with major depressive disorder , partial or nonresponse to 2 adequate antidepressant trials during the current episode , and currently using a selective serotonin reuptake inhibitor were r and omized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo , in addition to their existing selective serotonin reuptake inhibitor regimen , for 6 weeks . The main outcome measure was the Hamilton Rating Scale for Depression score . Results : The mean age was 46.4 ± 10.8 years ; mean total testosterone level , 417.5 ± 197 ng/dL ; mean baseline Hamilton Rating Scale for Depression score , 22.2 ± 5.2 ; and median duration of the current depressive episode , 6.3 ± 10.6 years . Hamilton Rating Scale for Depression scores decreased significantly in both testosterone ( 8.4 ) and placebo ( 7.4 ) groups . Antidepressant response , defined as a 50 % decline in Hamilton Rating Scale for Depression score , was achieved by 53.8 % ( 7/13 ) in the testosterone group and 23.1 % ( 3/13 ) in the placebo group ( P = 0.226 ) . Conclusion : Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood ; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression OBJECTIVE Testosterone supplementation may produce antidepressant effects in men , but until recently it has required cumbersome parenteral administration . In an 8-week r and omized , placebo-controlled trial , the authors administered a testosterone transdermal gel to men aged 30 - 65 who had refractory depression and low or borderline testosterone levels . METHOD Of 56 men screened , 24 ( 42.9 % ) displayed morning serum total testosterone levels of 350 ng/dl or less ( normal range=270 - 1070 ) . Of these men , 23 entered the study . One responded to an initial 1-week single-blind placebo period , and 22 were subsequently r and omly assigned : 12 to 1 % testosterone gel , 10 g/day , and 10 to identical-appearing placebo . Each subject continued his existing antidepressant regimen . Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial . RESULTS The groups were closely matched on baseline demographic and psychiatric measures . Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo . These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale . A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory . One subject assigned to testosterone reported increased difficulty with urination , suggesting an exacerbation of benign prostatic hyperplasia ; no other subject reported adverse events apparently attributable to testosterone . CONCLUSIONS These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels The effect of acute testosterone administration on exercise-induced myocardial ischemia was assessed in 14 men with coronary artery disease and low plasma testosterone concentrations in a study of r and omized , double-blind , crossover design . Testosterone increased time to 1-mm ST-segment depression compared with placebo by 66 ( 15 to 117 ) seconds ( p = 0.016 ) , suggesting a beneficial effect of testosterone on myocardial ischemia in these patients A double-blind comparison was made of the effects of testosterone undecanoate ( TU ) and placebo on sexual potency  of 29 impotent men ages 45–75 . The main criteria for inclusion in the study were a reduced or nonexistent capacity to have an erection during intercourse and no clinical signs of endocrinological pathology . All patients received placebo for 2 weeks . Then TU was given at a daily dose of 120 mg to 13 patients selected at r and om while the other patients continued to receive placebo . After 8 weeks all patients received placebo again for 2 weeks . An improvement in sexual potency was reported by five patients given TU and eight patients given placebo , with no significant differences between the groups . Treatment with TU influenced neither the hypothalamic-pituitary-gonadal axis , as judged by levels of prolactin , LH , FSH , and the LHRH-induced LH/FSH response , nor depression , anxiety , and somatic scores or performance tests . The only specific effect of TU treatment was to decrease the total plasma testosterone level . The present findings show pharmacotherapy with and rogens to be no more effective than placebo in restoring sexual potency to sexually impotent men without and rogen deficiency . Further studies may be needed to eluci date fully the effects of and rogen administration on psychological and endocrinological variables in such patients PURPOSE We compare the efficacy of testosterone gel ( T-gel ) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone . MATERIAL S AND METHODS A r and omized , placebo controlled , double-blind , parallel group , multicenter study was performed . A total of 75 hypogonadal men ( 18 to 80 years old , morning serum total testosterone 400 ng/dl or less ) with confirmed lack of response to sildenafil monotherapy were r and omized ( 1:1 ) to receive a daily dose of 1 % T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period . Subjects were evaluated for sexual function , primarily based on the International Index of Erectile Function ( IIEF ) , quality of life and serum testosterone levels at baseline and weeks 4 , 8 and 12 . RESULTS Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo , reaching statistical significance at week 4 ( 4.4 vs 2.1 , p = 0.029 , 95.1 % CI 0.3 , 4.7 ) . Similar trends were observed for improvements in orgasmic function , overall satisfaction , total IIEF score and percentage of IIEF responders . T-gel significantly ( p < or = 0.004 ) increased total and free testosterone levels throughout the study , although no significant correlations were made between testosterone levels and the IIEF at end point . CONCLUSIONS T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone INTRODUCTION Addition of testosterone ( T ) may improve the action of phosphodiesterase type 5 inhibitors ( PDE5-Is ) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels . AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is  and to specify the baseline T levels at which such an effect becomes significant . METHODS A multicenter , multinational , double-blind , placebo-controlled study of 173 men , 45 - 80 years , nonresponders to treatment with different PDE5-Is , with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day ( OAD ) for 4 weeks ; if not successful , they were r and omized in a double-blind , placebo-controlled design to receive placebo or a 1 % hydroalcoholic T gel ( 50 mg/5 g gel ) , to be increased to 10 mg T if results were clinical ly unsatisfactory . Main Outcomes Measures . Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses ( Sexual Encounter Profile 3 question ) . RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups . In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL , no additional effect of T administration to men optimally treated with PDE5-Is was encountered . The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks . Furthermore , addition of T to this PDE5-I regimen is beneficial , but only in hypogonadal men with baseline T levels ≤ 3 PURPOSE Determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and testosterone on strength , muscle mass , and function in hypogonadal elderly male recuperative care patients . METHODS Between 1999 and 2004 , 71 subjects ( mean age 78.2 + /- 6.4 yr , 86 % white ) were enrolled . After baseline one-repetition maximum ( 1RM ) strength testing and then r and omization to one of four treatment groups ( low-resistance ( 20 % of the 1RM ) exercises and weekly injections of either 100 mg of testosterone enanthate or placebo or high-intensity PRMST ( > or = 80 % 1RM ) and weekly injections ) , each subject received training and injections for 12 wk . RESULTS Ten subjects withdrew from the study before its completion . Based on intent-to-treat analyses , strength improved in all groups , but was greater with high-intensity PRMST compared with low-resistance exercise ( e.g. , leg press , ( mean + /- SE ) , 28 + /- 4 vs 13 + /- 4 % , P = 0.009 ) . Although testosterone led to significantly greater increases in midthigh cross-sectional muscle area compared with placebo ( 7.9 + /- 1.3 vs 2.4 + /- 1.4 % , P = 0.005 ) , it produced only a nonsignificant trend toward greater strength gains ( e.g. , leg press 25 + /- 4 vs 16 + /- 4 % , P = 0.144 ) . Change in aggregate functional performance score ( the sum of 4 functional performance test scores ) did not differ between the four intervention groups nor with high-intensity PRMST compared with low-resistance exercise ( 7 + /- 5 vs 15 + /- 5 % , P = 0.263 ) . There was not a significant interaction between exercise and testosterone for any outcome . CONCLUSION High-intensity PRMST is as safe and well tolerated as a similarly structured low-resistance exercise regimen for very frail elderly patients , but produces greater muscle strength improvements . The addition of testosterone leads to greater muscle size and a trend toward greater strength but did not produce a synergistic interaction with exercise . Neither intervention had a significant effect on functional performance 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 BACKGROUND Anabolic and rogen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem . The biological mechanisms underlying behavioral symptom development are poorly understood . SUBJECTS AND METHODS We examined levels of monoamine metabolites , neurohormones , and neuropeptides in the cerebrospinal fluid ( CSF ) of 17 healthy men , at baseline and following 6 days of  methyltestosterone ( MT ) administration  ( 3 days of 40 mg/d , then 3 days of 240 mg/d ) . Subjects received MT or placebo in a fixed sequence , with neither subjects nor raters aware of the order . Potential relationships were examined between CSF measures , CSF MT levels , and behavioral changes measured on a visual analog scale . RESULTS Following MT administration , levels of 3-methoxy-4-hydroxyphenylglycol ( MHPG ) were significantly lower ( mean + /- SD , 103.8 + /- 47 vs 122.0 + /- 50.7 pmol/mL ; P<.01 ) , and 5-hydroxyindoleacetic acid ( 5-HIAA ) levels were significantly higher ( mean + /- SD , 104.7 + /- 31.3 vs 86.9 + /- 23.6 pmol/mL ; P<.01 ) . No significant MT-related changes were observed in CSF levels of corticotropin , norepinephrine , cortisol , arginine vasopressin , prolactin , corticotropin-releasing hormone , beta-endorphin , and somatotropin release-inhibiting factor . Changes in CSF 5-HIAA significantly correlated with increases in " activation " symptoms ( energy , sexual arousal , and diminished sleep ) ( r = 0.55 ; P = .02 ) . No significant correlation was observed between changes in CSF and plasma MT , CSF MHPG , and behavioral symptoms . CONCLUSIONS Short-term anabolic and rogenic steroid use affects brain neurochemistry , increasing CSF 5-HIAA and decreasing MHPG . Changes in 5-HIAA levels caused by anabolic and rogenic steroids are related to the behavioral changes we observed . In this small sample , we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT CONTEXT There is a compelling need for therapies that prevent , defer the onset , slow the progression , or improve the symptoms of Alzheimer disease ( AD ) . OBJECTIVE To evaluate the effects of testosterone therapy on cognition , neuropsychiatric symptoms , and quality of life in male patients with mild AD and healthy elderly men . DESIGN Twenty-four-week , r and omized , double-blind , placebo-controlled , parallel-group study . SETTING Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles , San Francisco , and Irvine . PATIENTS OR OTHER PARTICIPANTS Sixteen male patients with AD and 22 healthy male control subjects . Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics . INTERVENTION Testosterone and placebo , in the form of hydroalcoholic gel ( 75 mg ) , were applied daily to the skin of the participants . MAIN OUTCOME MEASURES Instruments assessing cognitive functioning ( Alzheimer 's Disease Assessment Scale-Cognitive Subscale , California Verbal Learning Test , Block Design Subtest , Judgment of Line Orientation , Developmental Test of Visual-Motor Integration ) , neuropsychiatric symptoms ( Neuropsychiatric Inventory ) , global functioning ( Clinician 's Interview-Based Impression of Change ) , and quality of life ( Quality of Life-Alzheimer Disease Scale ) . RESULTS For the patients with AD , the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality -of-life scale ( P = .01 ) . No significant treatment group differences were detected in the cognitive scores at end of study , although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo . In the healthy control group , a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group ( P = .09 ) compared with placebo treatment . No difference between the treatment groups was detected in the remaining outcome measures . Testosterone treatment was well tolerated with few adverse effects relative to placebo . CONCLUSIONS Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD .  Testosterone had minimal effects on cognition Abstract Symptomatic and rogen deficiency is common in patients taking opioid analgesics , as these drugs potently suppress the hypothalamic – pituitary – gonadal axis . However , the efficacy of testosterone replacement in this setting remains unclear . The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other and rogen-dependent outcomes in men with opioid-induced and rogen deficiency . We conducted a r and omized , double-blind , parallel placebo-controlled trial at an outpatient academic research center . Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain , and total testosterone levels were < 350 ng/dL. Participants were r and omly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo . Primary outcomes were changes in self-reported clinical pain and objective ly assessed pain sensitivity . Sexual function , quality of life , and body composition were also assessed . The mean age was 49 years . The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm , respectively . Of the 84 r and omized participants , 65 had follow-up data on efficacy outcomes . Compared with men assigned to the placebo arm , those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia , sexual desire , and role limitation due to emotional problems . Testosterone administration was also associated with an improvement in body composition . There were no between-group differences in changes in self-reported pain . In conclusion , in men with opioid-induced and rogen deficiency , testosterone administration improved pain sensitivity , sexual desire , body composition , and aspects of quality of life The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind , placebo-controlled study on the effect of oral testosterone treatment on liver disease . At entry , 67 % ( 95 % confidence limits , 61%-74 % ) complained of sexual dysfunction .  Sexual dysfunction was significantly ( p less than 0.05 ) associated with lower serum concentrations of testosterone , non-protein-bound testosterone , and non-sex hormone-binding globulin-bound testosterone . The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared , however , when age , ethanol consumption , and severity of liver disease were included as covariates in the analysis . During follow-up ( median 30 mo , range 1 - 48 mo ) sexual dysfunction improved significantly ( p less than 0.05 ) at 6 , 12 , and 24 mo . Furthermore , the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period ( p less than 0.01 ) . However , the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function . In conclusion , oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men . However , sexual function improved after reduction of ethanol consumption in these patients The cardiovascular effects of testosterone treatment are debated . Osteoprotegerin ( OPG ) is an independent marker of cardiovascular risk . We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels . A r and omized , double-blinded , placebo-controlled study of 6 months testosterone therapy ( gel )  in 38 men aged 60 - 78 years with bioavailable testosterone < 7.3 nmol/l and waist circumference > 94 cm was performed .  Clinical evaluation , OPG , and C-reactive protein ( CRP ) measurements were carried out . Lean body mass ( LBM ) , total fat mass , and bone mineral density ( BMD ) were established by dual X-ray absorptiometry . Visceral adipose tissue ( VAT ) and subcutaneous adipose tissue ( SAT ) were measured by magnetic resonance imaging . Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM ( Δ LBM positive ) , n=14 . Data are presented as median ( interquartile range ) . Testosterone therapy  decreased total fat mass and SAT , whereas VAT was unchanged ( n=38 ) . OPG levels decreased during testosterone therapy ( from 2.0 ( 1.9 - 2.5 ) to 1.9 ( 1.6 - 2.2 ) ng/ml , p<0.05 vs. placebo ) , whereas CRP levels were unchanged ( n=38 ) . In responders to testosterone therapy ( n=14 ) , ΔOPG levels were inversely associated with ΔSAT ( r= - 0.60 , p=0.03 ) and positively associated with ΔVAT ( r=0.56 , p=0.04 ) . OPG levels  decreased during testosterone therapy suggesting decreased cardiovascular risk . Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution OBJECTIVES Older patients undergoing knee replacement surgery can recover more slowly than younger patients and require extended rehabilitation . Because administration of supraphysiological testosterone ( T ) dramatically increases strength , we hypothesized that preoperative T therapy would improve functional recovery and reduce hospital stay in older men undergoing knee replacement surgery . DESIGN Double-blinded , placebo-controlled pilot trial . SETTING A Veterans Affairs orthopedics clinic and inpatient postoperative unit . PARTICIPANTS Twenty-five men , mean age 70 , undergoing elective knee replacement . INTERVENTION Preoperative , supraphysiological T administration ( 600 mg T enanthate intramuscularly weekly for 4 weeks ) or sesame oil placebo . MEASUREMENTS Length of hospital stay and functional ability by Functional Independence Measure ( FIM ) score . RESULTS Mean length of hospital stay + /- st and ard deviation was nonsignificantly reduced in the T group ( 5.9 + /- 2.4 days vs 6.8 + /- 2.5 days ; P = .15 ) . At postoperative Day 3 , there was a significant improvement in ability to st and ( mean FIM score 5.2 + /- 1.0 vs 4.0 + /- 1.1 ; P = .04 ) and trends towards improvements in walking and stair climbing in the T group . There were no complications attributable to T therapy . CONCLUSIONS In older men undergoing knee replacement surgery , preoperative supraphysiological T administration may confer some clinical benefit . Future studies using longer courses of preoperative T administration in larger numbers of older men undergoing knee replacement surgery are warranted BACKGROUND The role of sex hormones in the prevention of cognitive decline is uncertain . Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function . But , there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment . METHODS In this pilot study , 11 men ( mean age 80 + /- 5 years , range 73 - 87 years ) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl ( lower limit for adult normal range ) were r and omized to receive intramuscular testosterone ( 200 mg every 3 weeks ) or placebo for 12 weeks . Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex hormone binding globulin , estradiol , and estrone ) , Behave AD Question naire , Katz Activities of Daily Living , Geriatric Depression Scale , Digit Span , Clock Face Drawing , Clock Face Perception , Verbal Fluency , Trail-Making B , and International Prostate Symptom Score at baseline , 4 weeks , and 10 weeks . RESULTS All men completed the study . Total and bioavailable testosterone , estrone , and estradiol levels increased in men receiving testosterone , but no changes were detected in men receiving placebo . No significant changes were found in behavior following testosterone supplementation , nor was there evidence of change in depression or activities of daily living . No discernable changes were found in any of the cognitive tests . Symptoms of prostate hyperplasia remained unchanged in the testosterone ( 6.6 + 5.8 to 5.2 + 3.6 ; p = .39 ) and placebo ( 8.8 + 6.4 to 6.4 + 3.8 ; p = .15 ) groups , and prostate-specific antigen levels did not change significantly . CONCLUSION No significant changes in behavior , function , depression , or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment . This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors BACKGROUND It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range . The objective of this study was to compare the cognitive responses of older , eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation .  DESIGN R and omized , double-blind , placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline . SETTING Community dwelling participants . PARTICIPANTS Fifty-seven healthy , eugonadal , community dwelling male volunteers , mean age 67 years ( + /-11 years ) . INTERVENTIONS Participants were r and omized to receive weekly intramuscular ( i.m . ) injections of either 50 , 100 or 300 mg T enanthate or placebo ( saline ) injection for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , weeks 3 and 6 of treatment and after 6 weeks of wash-out . MAIN OUTCOME MEASURES Performance on cognitive tests of verbal and spatial memory . RESULTS Men with moderate increases in serum T and /or its metabolites demonstrated significant improvements in verbal and spatial memory . In contrast , men with large or low increases in circulating T levels , failed to demonstrate significant changes in memory . CONCLUSION These results suggest that in healthy older men , beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels . Large or no to low increases in T levels do not appear to appreciably effect cognition The objective of the study was to investigate the effects of dihydrotestosterone ( DHT ) gel on general well-being , sexual function , and the prostate in aging men . A total of 120 men participated in this r and omized , placebo-controlled study ( 60 DHT and 60 placebo ) . All subjects had nocturnal penile tumescence once per week or less , and ropause symptoms , and a serum T level of 15 nmol/liter or less and /or a serum SHBG level greater than 30 nmol/liter . The mean age was 58 yr ( range , 50 - 70 yr ) . Of these subjects , 114 men completed the study .  DHT was administered transdermally for 6 months , and the dose varied from 125 - 250 mg/d . General well-being symptoms and sexual function were evaluated using a question naire , and prostate symptoms were evaluated using the International Prostate Symptoms Score , transrectal ultrasonography , and assay of serum prostate-specific antigen . Early morning erections improved transiently in the DHT group at 3 months of treatment ( P < 0.003 ) , and the ability to maintain erection improved in the DHT group compared with the placebo group ( P < 0.04 ) . No significant changes were observed in general well-being between the placebo and the DHT group . Serum concentrations of LH , FSH , E2 , T , and SHBG decreased significantly during DHT treatment . Treatment with DHT did not affect liver function or the lipid profile . Hemoglobin concentrations increased from 146.0 + /- 8.2 to 154.8 + /- 11.4 g/liter , and hematocrit from 43.5 + /- 2.5 % to 45.8 + /- 3.4 % ( P < 0.001 ) . Prostate weight and prostate-specific antigen levels did not change during the treatment . No major adverse events were observed . Transdermal administration of DHT improves sexual function and may be a useful alternative for and rogen replacement . As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia , DHT may be beneficial , compared with aromatizing and rogens , in the treatment of aging men 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 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 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 OBJECTIVES The effects of supplemental testosterone on cognition , mood and wellbeing in ageing men are unclear . This study aim ed to assess the effect of 12-months of oral testosterone supplementation on cognitive function , mood and quality of life in elderly men with low-normal gonadal status , not specifically selected for cognitive or mood defects . METHODS A st and ard oral dose ( 80 mg twice daily ) of testosterone undecanoate ( TU ) or placebo was administered for one year to 76 healthy men 60 years or older . All men had a free testosterone index ( FTI ) 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 . A neuropsychological assessment including the trail making test ( part B ) , visuospatial ( VSP ) block design test , mini mental state exam ( MMSE ) , Geriatric Depression Scale ( GDS ) , a 5-point Likert and a 10-point visual analogue quality of life ( QoL ) scale , along with serum hormone measurements were obtained at baseline , 6 , and 12 months . RESULTS Although calculated bioavailable testosterone ( cBT ) and FTI were higher , and muscle mass increased after 12 months , there was no difference in scores on the trail making or VSP block tests , the MMSE , GDS or either of the QoL scales between the testosterone and placebo group . There was no relationship between baseline cBT or FTI and treatment effect for any of the outcome measures . CONCLUSIONS 12-month supplementation with oral TU does not affect scores on visuospatial tests or mood and quality of life scales in older men with low-normal gonadal status Objective : To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men . Background : Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass , osteoporosis , decreased sexual activity , and changes in cognition . Methods : Twenty-five healthy , community-dwelling volunteers , aged 50 to 80 years , completed a r and omized , double-blind , placebo-controlled study . Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo ( saline ) for 6 weeks . Cognitive evaluations were conducted at baseline , week 3 , and week 6 of treatment by use of a battery of neuropsychologic tests . Results : Circulating total testosterone was raised an average of 130 % from baseline at week 3 and 116 % at week 6 in the treatment group . Because of aromatization of testosterone , estradiol increased an average of 77 % at week 3 and 73 % at week 6 in the treatment group . Significant improvements in cognition were observed for spatial memory ( recall of a walking route ) , spatial ability ( block construction ) , and verbal memory ( recall of a short story ) in older men treated with testosterone compared with baseline and the placebo group , although improvements were not evident for all measures . Conclusions : The results suggest that short-term testosterone administration enhances cognitive function in healthy older men . However , it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels , or both . The potential role of testosterone vs its metabolites on cognition requires further research Objective : To determine the contribution of conversion of testosterone ( T ) to estradiol on cognitive processing in a population of healthy older men who received T supplementation .  Methods : Sixty healthy , community-dwelling volunteers aged 50 to 90 years completed a r and omized , double-blind , placebo-controlled study . Participants were r and omized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill ( T group , n = 20 ) , 100 mg testosterone enanthate plus 1 mg daily of anastrozole , an aromatase inhibitor ( oral pill ) , to block the conversion of T to estradiol ( AT group , n = 19 ) , or saline injection and placebo pill ( placebo group , n = 21 ) for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , week 3 and week 6 of treatment , and after 6 weeks of washout . Results : Circulating total T was increased from baseline an average of 238 % in the T and AT treatment groups . Estradiol increased an average of 81 % in the T group and decreased 50 % in the AT group during treatment . Significant improvements in spatial memory were evident in the AT and T treatment groups . However , only the group with elevated estradiol levels ( T group ) demonstrated significant verbal memory improvement . Conclusion : In healthy older men , improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol , whereas improvement in spatial memory occurs in the absence of increases in estradiol The current study evaluates the efficacy and safety of testosterone ( T ) gel 1 % augmentation on depressive symptoms and quality of life in treatment-resistant , depressed , hypogonadal men older than 50 years of age who are receiving antidepressants . The authors hypothesized that T augmentation would improve depressive symptoms and quality of life .  Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms . Participants were continued on their antidepressant and were r and omized to receive either placebo or active T gel ( 5 g ) to be applied once a day . Participants were tested on 6 occasions : screening visit , an initial session ( pretreatment ) , at 6 and 12 weeks during the first treatment condition , and at 18 and 24 weeks during the crossover condition . The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment . However , a statistical difference between placebo and testosterone treatment phases was not demonstrated . The limitations of the study , including the chronicity and severity of patients ’ depression , variability in T levels , and a small sample size , probably influenced the ability to detect a discernable difference . Nevertheless , the study shows that T gel augmentation may be helpful in hypogonadal males with depression . ( J Geriatr Psychiatry Neurol 2005 ; 18:20 - 24 Objective : Weight loss in HIV-infected patients is extremely common and is associated with increased morbidity and mortality . Decreased testosterone concentrations occur commonly in patients with HIV disease and are associated with weight loss . This study assessed the effect of testosterone therapy on HIV associated weight loss in patients with AIDS . Methods : Forty HIV-seropositive patients with CD4 + counts of < 2 × 105/l and weight loss greater than 5 % of usual body weight were r and omized in a double-blind manner to receive 200 mg of testosterone cypionate or placebo intramuscularly every 2 weeks for 3 months . Patients were then crossed to receive the alternate treatment for the next 3 months . Outcome variables included weight , skin fold measurement , a quality -of-life question naire , Karnofsky score , T-cell subset analysis , complete blood count , routine blood chemistry measurements and free testosterone concentration . Results : Thirty-nine patients entered the study . Of these , 35 completed the first 3-month period ( 18 on placebo , 17 on testosterone ) and 23 completed the whole 6 month trial . Analysis of these 23 patients did not show any significant differences between testosterone and placebo treatment . Analysis of the first 3 months only for the 35 patients who completed it did not show any significant difference between the effects of testosterone and placebo treatment on weight gain . Patients treated with testosterone reported improved overall well-being ( P = 0.03 ) and a trend towards increased muscle strength ( P = 0.08 ) . There was no difference between the two groups in terms of side-effects or other effects on hematopoetic , liver , renal or immune function . Conclusions : Treatment with testosterone cypionate compared with placebo did not result in significant weight gain .  Testosterone supplementation did appear to produce an improved overall sense of well-being and possibly some increase in muscle strength . This r and omized , double-blinded study does not confirm the results of other recent studies which show potential benefits of testosterone and its analogs when used as a treatment for weight loss in HIV-positive patients This double-blind placebo controlled , cross-over study was carried out to assess the effect of testosterone administration on sexual behavior mood , and psychological symptoms in healthy men with erectile dysfunction . Biweekly injections of 200 mg of testosterone enanthate were given over a period of 6 weeks separated by a washout period of 4 weeks . Blood sample s for hormonal assessment , behavioral and psychological ratings were obtained prior to each injection . Luteinizing hormone remained significantly depressed but circulating testosterone had returned to baseline levels by 2 weeks following each hormonal injection . The ejaculatory frequency during the testosterone phase was statistically higher than during the placebo phase . There were marked , although statistically nonsignificant , increases in median frequency of reported sexual desire , masturbation , sexual experiences with partner , and sleep erections during the testosterone period . Testosterone did not have demonstrable effects on ratings of penile rigidity and sexual satisfaction . Mood variables and psychological symptoms did not change following hormonal administration . Results suggest that and rogen administration to eugonadal men with erectile dysfunction may activate their sexual behavior without enhancing erectile capacity and without effects on mood and psychological symptoms Because testosterone has an anabolic effect in myotonic dystrophy , we conducted a 12-month , r and omized , double-blind therapeutic trial of testosterone enanthate ( 3 mg/kg/wk ) in 40 men with myotonic dystrophy . We evaluated strength by manual muscle tests , quantitative myometry , pulmonary function , and quantitative functional assessment . A sustained , significant elevation of testosterone levels was produced but there was no effect on any measurement of muscle strength . Muscle mass as estimated by creatinine excretion and lean body mass ( 40 K method ) increased significantly . We conclude that testosterone does not improve strength in myotonic dystrophy despite increasing muscle mass 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 Background : Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia , adverse clotting profiles , obesity , and insulin resistance . Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease . Objective : This r and omised single blind placebo controlled crossover study compared testosterone replacement therapy ( Sustanon 100 ) with placebo in 10 men with ischaemic heart disease and hypogonadism . Results : Baseline total testosterone and bioavailable testosterone were respectively 4.2 ( 0.5 ) nmol/l and 1.7 ( 0.4 ) nmol/l . After a month of testosterone , delta value analysis between testosterone and placebo phase showed that mean ( SD ) trough testosterone concentrations increased significantly by 4.8 ( 6.6 ) nmol/l ( total testosterone ) ( p = 0.05 ) and 3.8 ( 4.5 ) nmol/l ( bioavailable testosterone ) ( p = 0.025 ) , time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 ( 54 ) seconds ( p = 0.002 ) , and mood scores assessed with vali date d question naires all improved . Compared with placebo , testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 ( 0.54 ) mmol/l ( p = 0.04 ) and −1.8 ( 2.4 ) pg/ml ( p = 0.05 ) respectively . Conclusion : Testosterone replacement therapy  in hypogonadal men delays time to ischaemia , improves mood , and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P<.001 ) . Within the overall null effect , there was a statistically significant time trend , with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue Purpose . Supplemental administration of and rogens has been advocated for men with sexual dysfunction ( SD ) and hypo and rogenism . The preponderance of evidence indicates that most delivery forms of testosterone ( T ) are effective but the role of dehydroepi and rosterone ( DHEA ) is controversial . A placebo-controlled , r and omized trial of oral and rogen ( T versus DHEA ) supplementation was carried out to determine their efficacy . Material s and methods . Eighty-six men with SD and decreased levels of serum T and /or DHEA , participated in a study receiving oral T undecanoate ( OTU ) ( n = 29 ) 80 mg twice daily , DHEA ( n = 28 ) 50 mg twice daily , or placebo ( n = 29 ) . Outcomes included evaluation of sexual performance by the International Index of Erectile Function ( IIEF ) , the And rogen Deficiency in the Aging Male ( ADAM ) , Aging Male Symtom Scale ( AMS ) , and Global Assessment Question naire ( GAQ ) question naires . Biochemical evaluations included measurement of T and DHEA , prolactin , gonadotropins , and PSA . Results . Seventy-nine men completed the study . There were no significant differences in outcomes as assessed by four different instruments : the ADAM , IIEF , AMS , and GAQ in regard to sexual interest or erectile function . Biochemically , a significant increase in serum DHEA between baseline and final visit was documented in the group receiving DHEA . The levels of T , on the other h and , increased insignificantly between entry and final visit in the T cohort . No biochemical changes were observed in the placebo group . Levels of PSA remained stable in all three groups . Conclusions . This study did not suggest a clinical benefit of OTU or DHEA supplementation in men with hypo and rogenism and SD . The recommended dose of OTU may have been inadequate or poorly absorbed . Increased doses or an alternative T delivery form may result in a different response BACKGROUND To determine the effect of oral testosterone supplementation on systemic low- grade inflammation measured by high-sensitive C-reactive protein ( hs-CRP ) in aging men with low testosterone levels . METHODS Two hundred thirty-seven men aged 60 to 80 years with a testosterone level of < 13.7 nmol/L ( below the 50th percentile of the population distribution ) were recruited into a double-blind r and omized placebo-controlled trial . Participants were r and omized to either 4 capsules of 40 mg testosterone undecanoate ( And riol Testocaps , NV Organon , Oss , The Netherl and s ) or placebo daily for 26 weeks . Serum levels of hs-CRP were measured at baseline and at 26 weeks using a near-infrared particle immunoassay of the Synchron LX System ( Beckman Coulter , Fullteron , CA ) . RESULTS The median baseline hs-CRP level was 1.95 mg/L ( 0.30 - 6.43 ) in the testosterone group compared with 1.90 mg/L ( 0.40 - 5.91 ) in the placebo group . After 26 weeks of testosterone supplementation therapy , the 2 intervention groups were not statistically significantly different ( median hs-CRP 2.20 vs 2.00 mg/L , interquartile range 0.40 - 6.54 vs 0.50 - 5.70 , P = .36 ) . In subgroup analysis , neither baseline testosterone level , nor age , nor baseline CRP-level modified the effect of testosterone supplementation on CRP levels . CONCLUSION Oral testosterone undecanoate supplementation , in dosage of 160 mg daily for 26 weeks , does not increase hs-CRP levels in elderly men OBJECTIVE To examine the effects of hypnotic suggestions or the administration of testosterone or trazodone to impotent men with no detectable organic cause for the impotence . PATIENTS AND METHODS The study comprised 79 men in whom clinical and laboratory examinations revealed no organic cause for their impotence : 20 men ( mean age 38.7 + /- 11.47 years ) received testosterone , 21 men ( mean age 39.5 + /- 10.73 years ) received trazodone , 20 men ( mean age 34.2 + /- 11.69 years ) underwent hypnosis and 18 men ( mean age 39.1 + /- 11.46 years ) served as controls . They were assessed by interview 4 , 6 and 8 weeks after starting treatment : the patient 's reports were verified by interviewing their partners . RESULTS Men who received a placebo had a 39 % improvement in sexual function , while the rates of improvement in the treated groups were higher , but not significantly so . The success rates of testosterone and trazodone treatment and hypnotic suggestions were 60 % , 67 % and 80 % , respectively . CONCLUSION Although the improvement was not statistically significant , treatment with testosterone and trazodone could be used as an adjuvant therapy in nonorganic male sexual dysfunction . The only treatment superior to placebo seemed to be hypnosis .  A more effective treatment may be obtained by combining these therapeutic modalities , but this needs further study CONTEXT Low testosterone levels in men have been associated with increased mortality . However , the influence of testosterone treatment on mortality in men with low testosterone levels is not known . OBJECTIVE The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels . DESIGN This was an observational study of mortality in testosterone-treated compared with untreated men , assessed with time-varying , adjusted Cox proportional hazards regression models . Effect modification by age , diabetes , and coronary heart disease was tested a priori . SETTING The study was conducted with a clinical data base that included seven Northwest Veterans Affairs medical centers . PATIENTS Patients included a cohort of 1031 male veterans , aged older than 40 yr , with low total testosterone [ ≤250 ng/dl ( 8.7 nmol/liter ) ] and no history of prostate cancer , assessed between January 2001 and December 2002 and followed up through the end of 2005 . MAIN OUTCOME MEASURE Total mortality in testosterone-treated compared with untreated men was measured . RESULTS Testosterone treatment was initiated in 398 men ( 39 % ) during routine clinical care . The mortality in testosterone-treated men was 10.3 % compared with 20.7 % in untreated men ( P<0.0001 ) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone . After multivariable adjustment including age , body mass index , testosterone level , medical morbidity , diabetes , and coronary heart disease , testosterone treatment was associated with decreased risk of death ( hazard ratio 0.61 ; 95 % confidence interval 0.42 - 0.88 ; P = 0.008 ) . No significant effect modification was found by age , diabetes , or coronary heart disease . CONCLUSIONS In an observational cohort of men with low testosterone levels  , testosterone treatment was associated with decreased mortality  compared with no testosterone treatment . These results should be interpreted cautiously because residual confounding may still be a source of bias . Large , r and omized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels CONTEXT Physical frailty is associated with reduced muscle strength , impaired physical function , and quality of life .  Testosterone ( T ) increases muscle mass and strength in hypogonadal patients . It is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T. OBJECTIVE Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men , on muscle mass and strength , physical function , and quality of life . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled , parallel-group , single-center study . PARTICIPANTS PARTICIPANTS were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter . METHODS Two hundred seventy-four participants were r and omized to transdermal T ( 50 mg/d ) or placebo gel for 6 months . Outcome measures included muscle strength , lean and fat mass , physical function , and self-reported quality of life . RESULTS Isometric knee extension peak torque improved in the T group ( vs. placebo at 6 months ) , adjusted difference was 8.6 ( 95 % confidence interval , 1.3 - 16.0 ; P = 0.02 ) Newton-meters . Lean body mass increased and fat mass decreased significantly in the T group by 1.08 + /- 1.8 and 0.9 + /- 1.6 kg , respectively . Physical function improved among older and frailer men . Somatic and sexual symptom scores decreased with T treatment ; adjusted difference was -1.2 ( -2.4 to -0.04 ) and -1.3 ( -2.5 to -0.2 ) , respectively . CONCLUSIONS T treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition , quality of life , and physical function . Further investigations are warranted to extend these results BACKGROUND Substantial loss of muscle mass occurs among men with AIDS wasting . OBJECTIVE To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting . DESIGN R and omized , controlled trial . SETTING University hospital . PATIENTS 54 eugonadal men with AIDS wasting ( weight < 90 % ideal body weight or weight loss > 10 % ) . INTERVENTION In a 2 x 2 factorial design , patients were assigned to receive testosterone enanthate ( 200 mg/wk ) or placebo injections and progressive resistance training ( three times weekly ) or no training for 12 weeks . MEASUREMENTS Cross-sectional muscle area and other indices of muscle mass . RESULTS Cross-sectional muscle area increased in response to training compared with nontraining ( change in arm muscle mass , 499 + /- 349 mm2 vs. 206 + /- 264 mm2 [ P = 0.004 ] ; change in leg muscle mass , 1106 + /- 854 mm2 vs. 523 + /- 872 mm2 [ P = 0.045 ] ) and in response to testosterone therapy compared with placebo ( change in arm muscle mass , 512 + /- 371 mm2 vs. 194 + /- 215 mm2 [ P < 0.001 ] ; change in leg muscle mass , 1,236 + /- 881 mm2 vs. 399 + /- 729 mm2 [ P = 0.002 ] ) . Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo ( -0.03 + /- 0.13 mmol/L vs. 0.05 + /- 0.13 mmol/L [ -1 + /- 5 mg/dL vs. 2 + /- 5 mg/dL ] ; P= 0.011 ) and increased in response to training compared with nontraining ( 0.05 + /- 0.13 mmol/L vs. 0.00 + /- 0.16 mmol/L [ 2 + /- 5 mg/dL vs. 0 + /- 6 mg/dL ] ; P = 0.052 ) . CONCLUSIONS In contrast to anabolic therapies that may have adverse effects on metabolic variables , supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting 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 BACKGROUND Relative and rogen deficiency in ageing males is assumed to have adverse health effects . This study assessed the effect of 12 months ' st and ard dose , oral testosterone , on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men . METHODS Testosterone undecanoate ( TU , 80 mg bid ) or placebo was administered for one year to 76 healthy men , 60 years or older , with a free testosterone index ( FTI ) of 0.3 - 0.5 and significant symptoms on a question naire design ed to evaluate and rogen deficiency ( ADAM ) . The ADAM was completed at baseline , 6 and 12 months . Hormone and safety data were collected at baseline , 1 , 3 , 6 and 12 months . RESULTS After 12 months , plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group ( P = 0.01 ) . FTI and calculated bioavailable testosterone ( cBT ) were greater in the testosterone group as compared with the placebo group ( P = 0.021 and 0.025 , respectively ) . There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU . However , there were trends toward improvements in sadness/grumpiness ( P = 0.063 ) , reduced erection strength ( P = 0.059 ) and decreased work performance symptoms ( P = 0.077 ) , particularly in men with baseline cBT levels below 3.1 nmol/l . CONCLUSIONS This study concludes that 80 mg bid oral TU does not improve overall ADAM question naire scores  in older men with low-normal gonadal status . Oral TU may preserve mood and erectile function , as assessed by this question naire , particularly in men with the lowest testosterone levels A r and omized , double-blind , placebo-controlled trial was conducted to ( 1 ) evaluate efficacy and safety of transdermal testosterone gel ( And roGel )  for hypogonadal men in Taiwan , and ( 2 ) observe improvements in sexual function through international index of erectile function ( IIEF ) scores . Eligible hypogonadal men were r and omized to receive 50 mg/day transdermal testosterone gel ( TTG ) or placebo for 3 months . Primary end point was change from baseline in total testosterone ( TT ) and free testosterone ( FT ) . Secondary end points were change from baseline in serum hormone levels ( such as dihydrotestosterone ( DHT ) , estradiol ( E2 ) , luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) and sex-hormone-binding globulin ( SHBG ) ) and changes in IIEF scores . Safety evaluations included adverse events ( AEs ) and skin irritation assessment . Compared with baseline , the  TTG  group ( n=20 ) had statistically significant increases in mean TT levels at month 1 ( P=0.024 ) and month 2 ( P=0.025 ) , but no significant changes at month 3 . TT levels in the placebo group ( n=18 ) showed no statistically significant change at any visit . Changes in FT levels paralleled changes in TT levels in both groups . TTG group IIEF scores were significantly increased at month 3 ( P=0.01 ) , compared with a decline in placebo scores . No drug-related AEs occurred in the TTG group ; the placebo group had 2 AEs ( mild skin rash ) . In conclusion , TTG effectively restores serum TT and FT levels to a normal physiological range for hypogonadal men in Taiwan and improves sexual function 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 There have not been studies assessing the effects of chronic testosterone cypionate ( TC ) therapy on circulating levels of testosterone ( T ) , estradiol ( E2 ) , free T , bioavailable T ( BAT ) , luteinizing hormone ( LH ) , and sexual function in impotent men with low T levels . This study was a double-blind crossover using 200 mg of TC or placebo given intramuscularly every 14 days for six injections and the other medication given for six doses . Blood was drawn before each injection . Mean concentrations of T , E2 , free T , and BAT were the same on TC or on placebo , but serum LH was significantly suppressed during intramuscular TC . With TC statistically significant improvements in libido and in potency were noted . Five of the men were able to have vaginal sex while taking TC . TC injections every 14 days do not appear to maintain increased T concentrations for 2 full weeks , and other dosage/injection schedules are being evaluated , but there were improvements in libido and potency Despite the widespread use of and rogen in the treatment of hypogonadal men , its efficacy in restoring sexual behavior to hypogonadal patients has not been established in appropriately controlled behavioral studies . Accordingly , testosterone enanthate or vehicle was injected once every 4 weeks i m in a double blind experiment . The subjects were six adult males , aged 32 - 65 yr , two with gonadal failure and four with secondary hypogonadism . Two doses of testosterone ( 100 and 400 mg ) were administered for approximately 5 months , with the treatments varied at r and om within and among subjects . Details of sexual activity and experience were followed by the use of daily logs . Frequencies of erections , including nocturnal erections and coitus , showed significant dose-related responses to and rogen treatment which closely followed the fluctuations in the circulating testosterone level . As indicated by the Profile of Mood States test , behavioral responses did not appear to be mediated by changes in mood . We concluded that the stimulatory effects of testosterone on sexual activity are rapid , reliable , and not due to a placebo effect . To maintain plasma testosterone and adequate sexual function within normal levels , even high doses of testosterone enanthate should be given no less frequency than once every 3 weeks Symptoms of male hypogonadism such as low libido and erectile dysfunction ( ED ) respond to testosterone ( T ) replacement . In hypogonadal men with major depressive disorder ( MDD ) , the extent to which T replacement alleviates sexual symptoms of hypogonadism is not known . We conducted 6 week double-blind placebo-controlled clinical trial in men with low and low-normal T levels ( i.e. , total T ≤ 350 ng/dl ) and MDD . Men were r and omized to receive weekly intramuscular injections of either T enanthate 200 mg or sesame-seed oil ( placebo ) . The primary outcome measure was self-reported sexual functioning . We r and omized 30 patients . The mean age was 52(SD ± 8) years , mean T level 262.5(SD ± 8) ng/dl , and mean baseline Hamilton Rating Scale for Depression ( HAM-D ) score 21(SD ± 8) . At baseline , sexual function was low , with the majority reporting having had normal erectile and orgasmic functioning 0–1 time in the preceding month . All patients who received T achieved normalization of their T levels . The HAM-D scores decreased significantly in both T and placebo groups , and there were no significant between-group differences : reduction in mean HAM-D score from baseline to endpoint was 10.1 in patients who received T and 10.5 in those who received  placebo . Self-reported sexual functioning improved slightly in both groups ; a between-group difference was not detected . Both T replacement and placebo were associated with improvement in sexual function and mood , but differences between T and placebo were not distinguishable IMPORTANCE Testosterone use in older men is increasing , but its long-term effects on progression of atherosclerosis are unknown . OBJECTIVE To determine the effect of testosterone administration on sub clinical atherosclerosis progression in older men with low or low-normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Testosterone 's Effects on Atherosclerosis Progression in Aging Men ( TEAAM ) was a placebo-controlled , double-blind , parallel-group r and omized trial involving 308 men 60 years or older with low or low-normal testosterone levels ( 100 - 400 ng/dL ; free testosterone < 50 pg/mL ) , recruited at 3 US centers . Recruitment took place between September 2004 and February 2009 ; the last participant completed the study in May 2012 . INTERVENTIONS One hundred fifty-six participants were r and omized to receive 7.5 g of 1 % testosterone and 152 were r and omized  to receive placebo gel packets daily for 3 years . The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES Co primary outcomes included common carotid artery intima-media thickness and coronary artery calcium ; secondary outcomes included sexual function and health-related quality of life . RESULTS Baseline characteristics were similar between groups : patients were a mean age of 67.6 years ; 42 % had hypertension ; 15 % , diabetes ; 15 % , cardiovascular disease ; and 27 % , obesity . The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group ( mean difference adjusted for age and trial site , 0.0002 mm/year ; 95 % CI , -0.003 to 0.003 , P = .89 ) . The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group ( adjusted mean difference , -10.8 Agatston units/year ; 95 % CI , -45.7 to 24.2 ; P = .54 ) . Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone . Sexual desire , erectile function , overall sexual function scores , partner intimacy , and health-related quality of life did not differ significantly between groups . Hematocrit and prostate-specific antigen levels increased more in testosterone group . CONCLUSIONS AND RELEVANCE Among older men with low or low-normal testosterone levels , testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life . Because this trial was only powered to evaluate atherosclerosis progression , these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00287586 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 CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p<0.001 ) following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels  following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men  on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT  reduces dementia risk OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes AIMS Anabolic therapy with testosterone may be useful in the treatment of wasting associated with chronic heart failure but little is known about its cardiovascular actions . The aim of this study was to determine the acute haemodynamic effects of testosterone administration in men with heart failure . METHODS AND RESULTS Twelve men with stable chronic heart failure were enrolled in a double-blind , r and omised , placebo-controlled , cross-over trial . Subjects were given testosterone 60 mg or placebo via the buccal route and central haemodynamics were monitored over 6h , using a pulmonary flotation catheter . Subjects received the second treatment on day 2 and haemodynamic monitoring was repeated . Treatment was well tolerated . Compared with placebo , testosterone treatment result ed in a relative increase in cardiac output ( p<0.0001 , ANCOVA ) , with maximum treatment effect after 180 min ( 10.3+/-4.6 % increase from baseline , p=0.035 ; 95 % CI 0.8 - 19.8 ) . This was accompanied by reduction in systemic vascular resistance compared with baseline ( p<0.0001 , ANCOVA ) , with maximum treatment effect also at 180 min ( -17.4+/-9.6 % from baseline , p=0.085 ; 95 % CI -37.3 to + 2.6 ) . These maximal changes coincided with the peak elevation in serum bio-available testosterone . There was no significant change in any other haemodynamic parameter measured . CONCLUSIONS Administration of testosterone increases cardiac output acutely , apparently via reduction of left ventricular afterload Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow . Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease . However , the effects on myocardial perfusion are unknown . Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone . Twenty-two men ( mean age 57 ± 9 [ SD ] years ) were r and omly assigned to oral testosterone undecanoate ( TU ; 80 mg twice daily ) or placebo in a crossover study design . After each 8-week period , subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance , pulse-wave analysis , and endothelial function measurements using radial artery tonometry , blood sampling , anthropomorphic measurements , and quality -of-life assessment . Although no difference was found in global myocardial perfusion after TU compared with placebo , myocardium supplied by unobstructed coronary arteries showed increased perfusion ( 1.83 ± 0.9 vs 1.52 ± 0.65 ; p = 0.037 ) . TU decreased basal radial and aortic augmentation indexes ( p = 0.03 and p = 0.02 , respectively ) , indicating decreased arterial stiffness , but there was no effect on endothelial function . TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference , but had no effect on hemostatic factors , quality of life , and angina symptoms . In conclusion , oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries , in line with previous intracoronary findings . The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia The effects of and rogen withdrawal and replacement were investigated in six hypergonadotrophic and six hypogonadotrophic men with hypogonadism . A double blind cross‐over design was used comparing testosterone undecanoate ( T.U. , Organon International ) , 160 mg daily by mouth , with placebo . There was a significant effect of T.U. on all measures of sexual interest and behaviour . Sexual interest increased within the first week of T.U. administration , ejaculation usually returning within the second week . Behavioural responses were similar in the hyper‐ and hypogonadotrophic groups H igh and rogen levels in men have been regarded as a risk factor for coronary artery disease ( CAD ) . However , it has recently been demonstrated that supplements of and rogens inhibit atheroma formation in castrated male animals , suggesting that testosterone may be antiatherosclerotic . In men with angina pectoris , a significant inverse correlation was found between plasma testosterone levels and the extent of CAD , demonstrating that low testosterone levels could be a risk factor for CAD . Other reports suggest that testosterone replacement therapy in men with CAD has a beneficial effect on angina pectoris and exercise-induced ST-segment depression . Another study showed that testosterone enhanced endotheliumindependent coronary artery dilation and flow-mediated brachial arterial vasoreactivity in men with CAD . In this study , we assessed the effects of oral testosterone administration on brachial arterial vasoreactivity in men with CAD . • • • Thirty-five men ( aged 58 8 years ) with CAD were r and omized to placebo ( n 17 ) or treatment group ( n 18 ) . Demographics of the study group are summarized in Table 1 . Diagnostic criteria of CAD are a history of unstable and stable angina pectoris with angiographic evidence ( 50 % stenosis of lumen diameter ) . Exclusion criteria were inflammatory disease or malignancy , ejection fraction 45 % , clinical evidence of heart failure , and Q-wave myocardial infa rct ion within 3 months before the study . The treatment group completed oral administration of 160 mg of testosterone undecanoate ( And riol , N.V. Organon , Oss , The Netherl and s ) daily for 4 weeks followed by 80 mg testosterone undecanoate for 8 weeks , in addition to their current medication . Using high-resolution ultrasound , we assessed brachial arterial vasoreactivity to reactive hyperemia ( flow-mediated dilation ) and sublingual nitroglycerin ( nitroglycerin-mediated dilation ) at baseline and after 12 weeks of treatment . Patients taking nitrates discontinued therapy 24 hours before the study to avoid nitrate tolerance . A 10-MHz linear phased-array ultrasound transducer ( GE Vigmed Ultrasound , Horten , Norway ) was used to image the dominant arm brachial artery longitudinally 3 to 5 cm just above the antecubital fossa . All patients rested in the supine position for 10 minutes in a quiet room . After the depth and gain setting were optimized to identify the vessel wall , the brachial artery diameter was measured from the anterior to the posterior interface between the media and the adventitia and determined at end-diastole on B mode . Reactive hyperemia was induced by inflation and then deflation of a pneumatic cuff placed around the upper arm . The blood pressure cuff was inflated to 250 mm Hg for 5 minutes . After release of the cuff , brachial artery diameter was measured within the first 15 seconds of reactive hyperemia . The brachial artery was allowed to return to the baseline level until 10 minutes after cuff release . Then , a further baseline brachial artery diameter was obtained . Nitroglycerin , 0.6 mg , was then given sublingually , and the brachial artery diameter was measured for the ensuing 3 minutes . The percent change in diameter caused by reactive hyperemia was calculated by dividing the difference from baseline end-diastolic diameter by the baseline value . The percent change in diameter caused by nitroglycerin administration was also calculated in the same way . Blood pressure and heart rate were measured before the examination . All data were calculated as an average of 4 consecutive cardiac cycles . Early morning blood sampling for fasting lipid profiles was performed and plasma-free testosterone levels were obtained immediately before ultrasound imaging and 12 weeks later . A st and ard radioimmunoassay method was used for analysis ( DSL-4900 kit , Diagnostic System Laboratory Inc. , Houston , Texas ) . All descriptive data are presented as mean SD and analyzed using SPSS for Windows 9.0 ( SPSS Inc. , Chicago , Illinois ) From the Cardiology Division , Yonsei Cardiovascular Center and Cardiovascular Research Institute , College of Medicine , Seoul ; and Department of Food and Nutrition , College of Ecology , Yonsei University , Seoul , South Korea . Dr. Jang ’s address is : Cardiology Division , Yonsei Cardiovascular Center , Yonsei University College of Medicine , 134 , Shinchon-Dong , Seodaemun-Gu , Seoul 120 - 752 , South Korea . E-mail : jangys1212@yumc.yonsei.ac.kr . Manuscript received August 10 , 2001 ; revised manuscript received and accepted December 10 , 2001 . TABLE 1 Clinical Characteristics of Study OBJECTIVE The objective of the study was to assess the effect of T treatment on constitutional and sexual symptoms in men with type 2 diabetes ( T2D ) . DESIGN This was a r and omized double-blind , parallel , placebo-controlled trial . SETTING The study was conducted at a tertiary referral center . PATIENTS Men aged 35 - 70 years with T2D , a hemoglobin A1c less than 8.5 % , and a total T level less than 12.0 nmol/L ( 346 ng/dL ) with mild to moderate aging male symptoms and erectile dysfunction . INTERVENTION Eighty-eight participants were r and omly assigned to 40 weeks of i m T undecanoate ( n = 45 ) or matching placebo ( n = 43 ) . MAIN OUTCOME MEASURES Constitutional symptoms using the aging male symptoms ( AMS ) score , sexual desire ( question 17 AMS score ) , and erectile function ( International Index of Erectile Function-5 ) . RESULTS T treatment did not substantially improve aging male symptoms [ mean adjusted difference ( MAD ) in change over 40 weeks across the T and placebo groups in AMS total score , -0.9 ( 95 % confidence interval [ CI ] -4.1 , 2.2 ) , P = .67 ] or sexual desire [ MAD in question 17 AMS , -0.3 ( 95 % CI -0.8 , 0.2 ) , P = .17 ] . Although compared with placebo , erectile function in men assigned to T was reduced [ MAD in International Index of Erectile Function abridged version 5 , -2.0 ( 95 % CI -3.4 , -0.6 ) , P < .02 ] , there was no significant difference between baseline and 40-week International Index of Erectile Function abridged version 5 scores if both groups were analyzed separately . At baseline , symptoms were worse in men with depression and microvascular complications but did not correlate with T levels . CONCLUSIONS In this trial , T treatment did not substantially improve constitutional or sexual symptoms in obese , aging men with T2D with mild to moderate symptoms and modest reduction in T levels typical for the vast majority of such men OBJECTIVE Testosterone deficiency is associated with significant morbidity , and and rogen replacement in overt hypogonadism is clearly beneficial . However , there are few data concerning the response to therapy in young men with mild testosterone deficiency We examined the effects of GH and /or testosterone ( T ) administration on body composition , performance , mood , sexual function , bone turnover , and muscle-gene expression in healthy older men . Ten men [ mean ( SEM ) age , 68 ( 2.5 ) yr ; height , 171.5 ( 2.4 ) cm ; and weight , 80 ( 3.0 ) kg ] completed each of the following 1-month , double-blind interventions after a baseline ( B ) study in r and omized order with an intervening 3-month washout : transdermal T patch ( 5.0 mg/daily ) ; recombinant human GH ( 6.25 micro g/kg sc daily ) ; and combined hormones ( GHT ) . ANOVA with repeated measures was used to evaluate interventional effects . Integrated serum GH concentrations [ mean ( SEM ) ] were elevated comparably by GH and GHT : [ B = 363 ( 55 ) , GH = 1107 ( 120 ) , T = 459 ( 131 ) , and GHT = 1189 ( 46 ) micro g/liter.min ; P < 0.0001 ] . Serum IGF-I concentrations also increased commensurately after GH and GHT : [ B = 168 ( 14 ) , GH = 285 ( 16 ) , T = 192 ( 25 ) , and GHT = 294 ( 25 ) micro g/liter ; P < 0.0001 ] . GHT administration increased total estradiol : [ B = 110 ( 20 ) , GH = 106 ( 13 ) , T = 129 ( 13 ) , and GHT = 153 ( 17 ) pmol/liter ; P < 0.02 ] , and both T and GHT elevated free T : [ B = 12 ( 2.1 ) , GH = 11 ( 1.5 ) , T = 22 ( 2.8 ) , and GHT = 24 ( 2.5 ) pg/ml ; P < 0.0001 ] . No significant changes occurred in strength , flexibility , percentage body fat , or sexual function and mood . However , fat-free mass increased under combined GHT exposure : [ B = 55 ( 1.3 ) , GH = 56 ( 1.1 ) , T = 55 ( 1.5 ) , GHT = 57 ( 1.7 ) kg ; P < 0.03 ] . Balance improved in response to GH intervention ( P < 0.05 ) , as did 30-m walk time during T and GHT interventions [ B = 6.6 ( 0.3 ) , GH = 6.2 ( 0.7 ) , T = 5.9 ( 0.3 ) , GHT = 5.5 ( 0.3 ) sec ; P = 0.04 ] and stair climb time for all three interventions [ B = 32.2 ( 1.4 ) , GH = 29.8 ( 1.2 ) , T = 30.5 ( 1.4 ) , and GHT = 29.9 ( 1.2 ) sec ( P = 0.0034 ) , wherein the effects of GH , T , and GHT were different from that of B ] . Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration ( P < 0.05 , compared with B ) . Myostatin and and rogen receptor gene expression were not affected . Serum osteocalcin increased in response to the GH and GHT interventions : [ B = 4.8 ( 0.52 ) , GH = 5.7 ( 0.54 ) , T = 4.7 ( 0.33 ) , and GHT = 5.5 ( 0.39 ) ; P < 0.009 ] . There were no significant adverse events during 30 patient-months of intervention . We conclude that 1 month of GH and /or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression The aim of this study was to assess the effect of a low-dose testosterone on body composition and pulmonary function , as well as on quality of life , sexuality , and psychological symptoms in patients with chronic obstructive pulmonary disease ( COPD ) . Twenty-nine men with moderate to severe COPD were allocated to receive either 250 mg of testosterone or placebo intra-muscularly , every fourth week , during the 26 weeks study period . Fat-free mass increased in the treatment group ( P<0.05 ) , and a significant difference between the treatment and the control group was seen after 26 weeks ( P<0.05 ) . Fat mass decreased in the treatment group ( P<0.05 ) , and there was a significant difference between the treatment and the control group after 12 weeks ( P<0.01 ) . A significantly better erectile function was reported in the treatment group at the final visit ( P<0.05 ) , and the overall sexual quality of life was significantly better in the treatment group after 12 weeks ( P<0.05 ) . No improvement in pulmonary function was found . In conclusion , administration of a low-dose testosterone  to men with COPD for 26 weeks was associated with improvement of body composition , better erectile function and sexual quality of life . Furthermore , there were no clinical or biochemical side effects We investigated whether the and rogen type or application mode or testosterone ( T ) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men r and omly assigned to the following treatment groups : mesterolone 100 mg orally daily ( [ MES ] n = 12 ) , testosterone undecanoate 160 mg orally daily ( [ TU ] n = 13 ) , testosterone enanthate 250 mg intramuscularly every 21 days ( [ TE ] n = 15 ) , or a single subcutaneous implantation of crystalline T 1,200 mg ( [ TPEL ] n = 15 ) . The dosages were based on st and ard treatment regimens . Previous and rogen substitution was suspended for at least 3 months . Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol ( TC ) and triglyceride ( TG ) less than 200 mg/dL were included . After a screening period of 2 weeks , the study medication was taken from days 0 to 189 , with follow-up visits on days 246 and 300 . Before substitution , all men were clearly hypogonadal , with mean serum T less than 3 nmol/L in all groups . And rogen substitution led to no significant increase of serum T in the MES group , subnormal T in the TU group ( 5.7 + /- 0.3 nmol/L ) , normal T in the TE group ( 13.5 + /- 0.7 nmol/L ) , and high-normal T in the TPEL group ( 23.2 + /- 1.1 nmol/L ) . 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline . Compared with presubstitution levels , a significant increase of TC was observed in all treatment groups ( TU , 14.4 % + /- 3.0 % ; MES , 18.8 % + /- 2.5 % ; TE , 20.4 % + /- 3.0 % ; TPEL , 20.2 % + /- 2.6 % ) . Low-density lipoprotein cholesterol ( LDL-C ) also increased significantly by 34.3 % + /- 5.5 % ( TU ) , 46.4 % + /- 4.1 % ( MES ) , 65.2 % + /- 5.7 % ( TE ) , and 47.5 % + /- 4.3 % ( TPEL ) . High-density lipoprotein cholesterol ( HDL-C ) showed a significant decrease by -30.9 % + /- 2.8 % ( TU ) , -34.9 % + /- 2.5 % ( MES ) , -35.7 % + /- 2.6 % ( TE ) , and -32.5 % + /- 3.5 % ( TPEL ) . Serum TG significantly increased by 37.3 % + /- 11.3 % ( TU ) , 46.4 % + /- 10.3 % ( MES ) , 29.4 % + /- 6.5 % ( TE ) , and 22.9 % + /- 6.7 % ( TPEL ) . TU caused a smaller increase of TC than TE and TPEL , whereas the parenteral treatment modes showed a lower increase of TG . There was no correlation between serum T and lipid concentrations . Despite the return of serum T to pretreatment levels , serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation . In summary , and rogen substitution  in hypogonadal men increases TC , LDL-C , and TG and decreases HDL-C independently of the and rogen type and application made and the serum and rogen levels achieved . Due to the extended washout period for previous and rogen medication and the exclusion of men with preexisting hyperlipidemia , this investigation demonstrates more clearly than previous studies the impact of and rogen effects on serum lipids and lipoproteins . It is concluded that preexisting low serum and rogens induce a " male-type " serum lipid profile , and increasing serum and rogens further within the male normal range does not exert any additional effects . The threshold appears to be above the normal female and rogen serum levels and far below the lower limit of normal serum T levels in adult men . These findings may have considerable implication s for the use of and rogens as a male contraceptive and for and rogen therapy in elderly men PURPOSE Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients . Men with acquired immunodeficiency syndrome ( AIDS ) lose body cell mass . Hypogonadism is also common . This study tested the efficacy of a testosterone transscrotal patch ( 6 mg/day ) in improving body cell mass and treating hypogonadism in these patients . SUBJECTS AND METHODS This multicenter , r and omized , double-blinded , placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men , 18 years of age and older , who had AIDS , 5 % to 20 % weight loss , and either a low morning serum total testosterone level ( < 400 ng/dL ) or a low free testosterone level ( < 16 pg/mL ) . Outcomes included weight , body cell mass as measured using bioelectrical impedance analysis , quality of life , and morning measurements of serum testosterone and dihydrotestosterone levels , lymphocyte subsets , and HIV quantification . RESULTS There were no significant differences in baseline weight , CD4 cell counts , or HIV serum viral quantification between treatment arms . Morning total and free testosterone levels increased in those treated with testosterone , but not with placebo . Following 12 weeks of treatment there were no differences ( testosterone-placebo ) in mean weight change ( -0.3 kg [ 95 % confidence interval ( CI ) : -1.4 to 0.8 ] ) or body cell mass ( -0.2 kg [ 95 % CI : -1.0 to 0.6 ] ) in the two groups . There were also no changes in quality of life in either group . CONCLUSION Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch . However , this system of replacement does not improve weight , body cell mass , or quality of life BACKGROUND Dehydroepi and rosterone ( DHEA ) and testosterone are widely promoted as antiaging supplements , but the long-term benefits , as compared with potential harm , are unknown . METHODS We performed a 2-year , placebo-controlled , r and omized , double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA . Among the men , 29 received DHEA , 27 received testosterone , and 31 received placebo . Among the women , 27 received DHEA and 30 received placebo . Outcome measures included physical performance , body composition , bone mineral density ( BMD ) , glucose tolerance , and quality of life . RESULTS As compared with the change from baseline to 24 months in the placebo group , subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter ( 9.2 micromol per liter ) in men and by 3.8 microg per milliliter ( 10.3 micromol per liter ) in women . Among men who received testosterone , the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter ( 1.1 nmol per liter ) , as compared with the change in the placebo group . A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements . Neither hormone altered the peak volume of oxygen consumed per minute , muscle strength , or insulin sensitivity . Men who received testosterone had a slight increase in fat-free mass , and men in both treatment groups had an increase in BMD at the femoral neck . Women who received DHEA had an increase in BMD at the ultradistal radius . Neither treatment improved the quality of life or had major adverse effects . CONCLUSIONS Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition , physical performance , insulin sensitivity , or quality of life . ( Clinical Trials.gov number , NCT00254371 [ Clinical Trials.gov ] . ) OBJECTIVE The objective of this study was to examine the relationship between anabolic-- and rogenic steroids and lipoprotein levels in men receiving weekly injections of gradually escalating doses of up to 600 mg/week of testosterone cypionate .  DESIGN The design was a placebo-controlled , double-blind , 24-week cross-over design in which subjects were r and omized to one of two treatment sequences : ( a ) weekly testosterone cypionate injections for 6 weeks , no treatment for 6 weeks , weekly placebo injections for 6 weeks , and then again no treatment for 6 weeks ; or ( b ) placebo , no treatment , testosterone , and then no treatment , with each interval also lasting 6 weeks as in the first sequence . SETTING The setting was a private hospital . PARTICIPANTS Participants were normal male volunteers . INTERVENTIONS Testosterone cypionate injections were given in gradually increasing doses of 150 mg/week for 2 weeks , 300 mg/week for 2 weeks , and 600 mg/week for 2 weeks . Eight subjects received testosterone injections during the first injection phase and placebo during the second injection phase , and the remaining eight subjects received placebo first and testosterone second . RESULTS We found a 21 % depression of high-density lipoprotein cholesterol ( HDL-C ) levels following the first 300-mg testosterone dose . This depression remained unchanged after the two 600-mg doses . In contrast , we did not find any changes in low-density lipoprotein or total cholesterol levels at any of the time points studied . Subjects ' total cholesterol/HDL-C ratios were significantly elevated during testosterone administration and even 4 weeks following the last injection . CONCLUSION Our findings suggest that testosterone cypionate adversely affects cholesterol fractions , that this effect reaches its full magnitude even at very modestly supraphysiologic doses , and that this effect persists for several weeks after discontinuation of the drug 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 OBJECTIVES To determine whether testosterone supplementation improves rehabilitation outcomes in ill older men . DESIGN A r and omized , placebo-controlled , double-blind study . SETTING A Geriatric Evaluation and Management ( GEM ) unit based at a university- affiliated Veterans Affairs Medical Center . PARTICIPANTS Fifteen men aged 65 to 90 years admitted to the GEM for rehabilitation . INTERVENTION Subjects were r and omized to receive weekly intramuscular injections with testosterone enanthate 100 mg or placebo . MEASUREMENTS Task-specific performance using the Functional Independence Measure ( FIM ) and grip strength was measured at the onset of the study and at the time of discharge from the GEM . RESULTS At baseline , FIM scores were similar between the placebo and the testosterone group ( 73.7 vs 70.7 , P = .637 ) , as was grip strength ( 49.7 vs 55.3 pounds , P = .555 ) . At discharge from the GEM , testosterone-treated patients had improved FIM scores compared with baseline ( 93.6 vs 70.7 ; P = .012 ) and grip strength ( 68.7 vs 55.3 pounds ; P = .033 ) . In the placebo group there was no significant improvement of FIM scores compared with baseline ( 78.0 versus 73.7 ; P = .686 ) or of grip strength ( 48.9 vs 49.7 pounds ; P = .686 ) . CONCLUSIONS Testosterone supplementation may improve rehabilitation outcomes in ill older men Testosterone replacement is the most effective treatment for  sexual dysfunction in hypogonadal men . Comorbid depression and antidepressant side effects may reduce its influence . The authors conducted a 6-week , double-blind , placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level . A total of 100 men were enrolled at 2 study sites ( Boston , Massachusetts , USA , and Tel Aviv , Israel ) . The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function ( IIEF ) . Complete pre- and posttrial IIEF data were available for 63 subjects . Men r and omized to testosterone ( n = 31 ) and placebo ( n = 32 ) were similar in age , baseline testosterone levels , and baseline IIEF scores . At study termination , men r and omized to placebo showed virtually no change from baseline in mean ( 95 % CI ) IIEF score ( −0.7 [ −6.5 , 5.2 ] ) , whereas those receiving testosterone exhibited a substantial increase ( 15.8 [ 8.5 , 23.1 ] ) . The estimated mean difference between groups was 16.8 [ 7.5 , 26.1 ] ; p = .001 by linear regression with adjustment for age and study site . There were also significant between-group differences in each of the 5 IIEF subscales , as well as on the single question involving ejaculatory ability ( p ≤ .03 in all cases ) . Effect sizes in these comparisons remained little changed , and generally remained statistically significant , when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale . It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels , suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone . In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants , treatment with exogenous testosterone was associated with a significant improvement in sexual function , particularly including ejaculatory ability Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders  in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression BACKGROUND Studies on the effect of estrogen on atherosclerotic coronary artery disease ( CAD ) risk in women have produced conflicting results . Similar confusion , but fewer data , exists on the effect of testosterone on CAD risk in men . METHODS We used 99mTc sestamibi single-photon emission computed tomography ( SPECT ) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men ( mean age , 69.1 + /- 6.4 years ) with provocable myocardial ischemia on st and ard medical therapy . Patients performed 3 exercise ( n = 18 ) or adenosine ( n = 16 ) stress tests during the infusion of placebo or 2 doses of testosterone design ed to increase testosterone 2 or 6 times baseline . RESULTS Serum testosterone increased 137 + /- 58 % and 488 + /- 113 % , and estradiol levels increased 27 + /- 46 % and 76 + /- 57 % , ( P < .001 for all ) during the 2 testosterone infusions . There were no differences among the placebo or testosterone groups in peak heart rate , systolic blood pressure , maximal rate pressure product , perfusion imaging scores , or the onset of ST-segment depression . CONCLUSIONS Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD The basis was established for a rational sex hormone therapy with the isolation of the estrogenicl 2 s and and rogenic hormones.3 It has been demonstrated by animal experiments that a basic effect of the sex hormones is hyperemization of the whole organism.4 4 When this observation was confirmed with regards to the skin in the 1930 ’s in patients treated for well defined gonad insufficiency , the possibility then existed of treating patients with diseases of the circulatory system with sex hormones 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 Mid-life onset male dysthymic disorder ( DD ) seems to be a distinct clinical condition with limited therapeutic options . Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy , though this strategy has received limited systematic study . We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone ( T ) level ( i.e , screening total serum testosterone < 350 ng/dL ) . Enrolled men were r and omized to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days . The primary outcome measures were the Clinical Global Impression ( CGI ) improvement score and the 21-item Hamilton Depression Rating Scale ( HDRS ) score . Twenty-three patients were r and omized . The mean ( SD ) age of the enrolled patients was 50.6 ( 7.0 ) years and that of total testosterone level was 339 ( 93 ) ng/dL. The median duration of the current dysthymic episode was 3.6 ( 2.3 ) years , and the mean ( SD ) HDRS was 14.0 ( 2.9 ) . After the intervention , the mean HDRS score decreased significantly more in the testosterone group ( 7.46 [ 4.56 ] ) than in the placebo group ( 1.8 [ 4.13 ] , t21 = −3.07 , P = 0.006 ) . Remission , defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8 , was achieved by 7 ( 53.8 % ) of 13 in the testosterone group and 1 ( 10 % ) of 10 in the placebo group ( P = 0.03 ) . Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia 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 OBJECTIVES This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity , ventilatory efficiency , muscle strength , insulin resistance , and baroreflex sensitivity ( BRS ) in elderly patients with chronic heart failure ( CHF ) . BACKGROUND CHF is characterized by a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function that could be involved in the pathophysiology of heart failure . METHODS Seventy elderly patients with stable CHF-median age 70 years , ejection fraction 31.8 + /- 7%-were r and omly assigned to receive testosterone ( n = 35 , intramuscular injection every 6 weeks ) or placebo ( n = 35 ) , both on top of optimal medical therapy . At baseline and at the end of the study , all patients underwent echocardiogram , cardiopulmonary exercise test , 6-min walk test ( 6MWT ) , quadriceps maximal voluntary contraction ( MVC ) , and isokinetic strength ( peak torque ) and BRS assessment ( sequences technique ) . RESULTS Baseline peak oxygen consumption ( VO(2 ) ) and quadriceps isometric strength showed a direct relation with serum testosterone concentration . Peak VO(2 ) significantly improved in testosterone but was unchanged in placebo .  Insulin sensitivity was significantly improved in testosterone . The MVC and peak torque significantly increased in testosterone but not in placebo . The BRS significantly improved in testosterone but not in placebo . Increase in testosterone levels was significantly related to improvement in peak VO(2 ) and MVC . There were no significant changes in left ventricular function either in testosterone or placebo . CONCLUSIONS These results suggest that long-acting testosterone therapy improves exercise capacity , muscle strength , glucose metabolism , and BRS in men with moderately severe CHF .  Testosterone benefits seem to be mediated by metabolic and peripheral effects OBJECTIVES To investigate the effects of testosterone supplementation on bone , body composition , muscle , physical function , and safety in older men . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING A major medical institution . PARTICIPANTS One hundred thirty-one men ( mean age 77.1 + /- 7.6 ) with low testosterone , history of fracture , or bone mineral density ( BMD ) T-score less than -2.0 and frailty . INTERVENTION Participants received 5 mg/d of testosterone or placebo for 12 to 24 months ; all received calcium ( 1500 mg/d diet and supplement ) and cholecalciferol ( 1,000 IU/d ) . MEASUREMENTS BMD of hip , lumbar spine , and mid-radius ; body composition ; sex hormones , calcium-regulating hormones ; bone turnover markers ; strength ; physical performance ; and safety parameters . RESULTS Ninety-nine men ( 75.6 % ) completed 12 months , and 62 ( 47.3 % ) completed end therapy ( mean 23 months ; range 16 - 24 months for 62 who completed therapy ) . Study adherence was 54 % , with 40 % of subjects maintaining 70 % or greater adherence . Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL , respectively , in the treatment group . BMD on testosterone  increased 1.4 % at the femoral neck and 3.2 % at the lumbar spine ( P=.005 ) and decreased 1.3 % at the mid-radius ( P<.001 ) . There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance . There were no differences in safety parameters . CONCLUSION Older , frail men receiving  testosterone replacement increased testosterone levels and had favorable changes in body composition , modest changes in axial BMD , and no substantial changes in physical function OBJECTIVE To investigate the effects of oral testosterone undecanoate ( TU ) on symptoms associated with late-onset hypogonadism ( LOH ) . Design Multicenter , r and omized , double-blind , placebo-controlled . METHODS The study was performed in 14 study centers in seven European countries . Men > or = 50 years ( n=322 ) with symptoms of hypogonadism and testosterone deficiency ( calculated free testosterone < 0.26 nmol/l ) were r and omized and treated for 12 months with placebo or oral TU 80 , 160 or 240 mg/day . Primary outcome was the total score on the Aging Males ' Symptoms ( AMS ) rating scale after six months of treatment . RESULTS Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU result ed in an improved total AMS score at month 6 , but differences between groups were not statistically significant . There was greater improvement in subjects < 60 years when compared with subjects > or = 60 years ( P=0.001 ) , but baseline testosterone level had no influence on treatment response . The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 ( P=0.008 ) and 12 ( P=0.012 ) compared with placebo , but not with 80 and 240 mg/day . Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates . CONCLUSIONS In one of the largest placebo-controlled studies of testosterone therapy in LOH , oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo , except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day BACKGROUND Erectile dysfunction and low testosterone levels frequently occur together . OBJECTIVE To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels . DESIGN R and omized , double-blind , parallel , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00512707 ) SETTING Outpatient academic research center . PARTICIPANTS Men aged 40 to 70 years with scores of 25 or less for the erectile function domain ( EFD ) of the International Index of Erectile Function , total testosterone levels less than 11.45 nmol/L ( < 330 ng/dL ) , or free testosterone levels less than 173.35 pmol/L ( < 50 pg/mL ) . INTERVENTION Sildenafil dose was optimized , and 140 participants were then r and omly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants . All participants were included in the primary analysis , although 10 in the testosterone group and 12 in the placebo group did not complete the study . RESULTS At baseline , the 2 groups had similar EFD scores . Administration of sildenafil alone was associated with a substantial increase in EFD score ( mean , 7.7 [ 95 % CI , 6.5 to 8.8 ] ) , but change in EFD score after r and omization did not differ between the groups ( difference , 2.2 [ CI , -0.8 to 5.1 ] ; P = 0.150 ) . The findings were similar for other domains of sexual function in younger men , more obese men , and men with lower baseline testosterone levels or an inadequate response to sildenafil alone . Frequency of adverse events was similar for testosterone and placebo groups . LIMITATION Whether testosterone could improve erectile function without sildenafil was not studied . CONCLUSION Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving  erectile function in men with erectile dysfunction and low testosterone levels . PRIMARY FUNDING SOURCE National Institute of Child Health and Human Development
target: Testosterone supplementation did not show consistent benefit for cardiovascular risk , sexual function , mood and behavior , or cognition .
  Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo .
  Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido .
  Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function .
  Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality , psychological well-being , or mood .
background: Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of " low testosterone " ( low-T ) for cardiovascular health , sexual function , muscle weakness or wasting , mood and behavior , and cognition .