Adverse events associated with testosterone administration. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study. Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses. Effect of androgen suppression compared with androgen receptor blockade on arterial stiffness in men with prostate cancer. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Relationship between serum levels of sex hormones and progression of subclinical atherosclerosis in postmenopausal women. Testosterone suppression in men with prostate cancer is associated with increased arterial stiffness Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Interrelation between plasma testosterone and plasma insulin in healthy adult men: the Telecom Study Low serum testosterone and mortality in older men. The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. ACE inhibitors for sarcopenia--as good as exercise training? Testosterone recovery in the off-treatment time in prostate cancer patients undergoing intermittent androgen deprivation therapy Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Which androgen replacement therapy for women? Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial
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 . 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 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 Objective . To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women . Methods . Fifty surgically postmenopausal women were included in this double-blind , placebo-controlled and r and omized study to receive daily oral treatment with estradiol valerate 2 mg + placebo ( E/P ) or estradiol valerate 2 mg + testosterone undecanoate 40 mg ( E/T ) for 24 weeks and then switched to the other regimen for another 24 weeks . Sex hormones , High sensitivity CRP ( hsCRP ) , Interleukin-6 ( IL-6 ) , Tissue necrosis factor (TNF)-α , Insulin-like growth factor binding globulin ( IGFBP-1 ) , vascular cell adhesion molecule (VCAM)- 1 , and homocysteine were analyzed at baseline and after 6 and 12 months . Results . Estradiol and and rogens increased as expected during the treatments . After 6 months of E/P , increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded , whereas IL-6 , TNF-α , and homocysteine were unchanged . When testosterone was added to estrogen , the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone . However , testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6 , TNF-α , and homocysteine . Conclusion . Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects . On the contrary , the estrogen-induced increase in hsCRP was suppressed BACKGROUND In primates , and rogens can play a synergistic role with FSH in promoting the early follicular recruitment , which is critical in assisted reproduction technique programmes . OBJECTIVE To assess whether poor responders can benefit from and rogen application . METHODS Inclusion criteria were a previous poor ovarian response to controlled ovarian stimulation and a decreased hormonal ovarian reserve . Selected women were r and omized to receive either transdermal application of testosterone ( n = 24 ) or placebo ( n = 25 ) gel for 15 days before FSH treatment for a second IVF cycle . Similar GnRH analogue and equivalent FSH daily doses were used in both cycles . The primary outcome was the total number of oocytes retrieved . RESULTS Testosterone gel application result ed in a significant increase in plasma testosterone levels but did not significantly improve the antral follicle count . Furthermore , after gel application , the main parameters of the ovarian response ( numbers of pre-ovulatory follicles , total and mature oocytes and embryos ) did not significantly differ between testosterone and placebo-treated patients . CONCLUSION No significant beneficial effects of and rogen administration on the ovarian response to FSH could be demonstrated . However , subsequent clinical trials are needed to determine whether an optimal dose and /or a longer duration of testosterone administration may be helpful 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 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 BACKGROUND Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of  cardiovascular events in men r and omized to testosterone  , result ing in enrollment cessation by trial 's Data and Safety Monitoring Board . We evaluated changes in gonadal hormones and markers of inflammation and coagulation to eluci date risk factors associated with cardiovascular events . METHODS Men aged 65 years or more , 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 . Changes in total and free testosterone , estradiol and estrone , C-reactive protein , interleukin 6 , fibrinogen , plasminogen activator inhibitor-1 , and pro-brain naturetic peptide were compared between groups and within the testosterone group between subjects who experienced cardiovascular events and those who did not . RESULTS Of 209 men r and omized ( mean age 74 years ) , gonadal hormones and biomarkers were available in 179 men . Baseline body mass index , gonadal hormones , lipids , Framingham risk scores , and other biomarkers were similar in the two treatment groups . Within the testosterone group , the 6-month increase in free testosterone was significantly greater in men who experienced cardiovascular events than in those who did not [ mean ( 95 % confidence interval ) , 10.6 ( 4.6 - 16.7 ) vs 5.2 ( 3.0 - 7.5 ) ng/dL , p = .05 ] . In multivariable logistic regression analysis , the change in the serum levels of free testosterone was associated with cardiovascular events . CONCLUSION Mobility-limited older men who experienced cardiovascular events had greater increases in serum free testosterone levels than those who did not BACKGROUND Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass ( FFM ) and skeletal muscle and decreases in fat mass ( FM ) but have not reported the impact of baseline body composition . OBJECTIVE The objective of the study was to determine the effect , in nonobese aging men with symptoms of and rogen deficiency and low-normal serum testosterone levels , of testosterone therapy on total and regional body composition and hormonal and metabolic indices . METHODS Sixty healthy but symptomatic , nonobese men aged 55 yr or older with total testosterone ( TT ) levels less than 15 nm were r and omized to transdermal testosterone patches or placebo for 52 wk . Body composition , by dual-energy x-ray absorptiometry ( FM , FFM , skeletal muscle ) and magnetic resonance imaging ( abdominal sc and visceral adipose tissue , thigh skeletal muscle , and intermuscular fat ) and hormonal and metabolic parameters were measured at wk 0 and 52 . RESULTS Serum TT increased by 30 % ( P = 0.01 ) , and LH decreased by 50 % ( P < 0.001 ) . Relative to placebo , total body FFM ( P = 0.03 ) and skeletal muscle ( P = 0.008 ) were increased and thigh skeletal muscle loss was prevented ( P = 0.045 ) with testosterone therapy and visceral fat accumulation decreased ( P = 0.001 ) without change in total body or abdominal sc FM ; change in visceral fat was correlated with change in TT levels ( r2 = 0.36 ; P = 0.014 ) . There was a trend to increasing total and low-density lipoprotein cholesterol with placebo . CONCLUSION Testosterone therapy , relative to placebo , selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass . Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk BACKGROUND The incidence of thrombotic cardiovascular disease is greater in men than in premenopausal women .  Testosterone has been implicated as a significant risk factor for cardiovascular disease and for acute myocardial infa rct ions and strokes in young male athletes who abuse anabolic steroids . Thromboxane A2 ( TXA2 ) is a vasoconstrictor and platelet proaggregatory agent that has been implicated in the pathogenesis of cardiovascular disease . We therefore tested the hypothesis that testosterone regulates the expression of human platelet TXA2 receptors . METHODS AND RESULTS In a double-blind , placebo-controlled , r and omized , parallel-group study , we determined the effects of testosterone cypionate 200 mg IM given twice , 2 weeks apart , or saline placebo in 16 healthy men .  Platelet TXA2 receptor density ( Bmax ) and dissociation constant ( Kd ) were measured by use of the TXA2 mimetic 125I-BOP . Platelet aggregation responses to I-BOP and to thrombin and plasma testosterone concentrations were measured before treatment ( pretreatment phase ) , at 2 and 4 weeks ( active phase ) , and again at 8 weeks ( recovery phase ) . Treatment with testosterone was associated with an increase in the Bmax value from 0.95 + /- 0.13 to 2.10 + /- 0.4 pmol/mg protein ( n = 9 ) , with a peak effect at 4 weeks ( P = .001 ) , returning to baseline by 8 weeks . There was no significant change in Bmax values in the saline-treated group . The Kd values were unchanged . Testosterone treatment was associated with a significant increase in the maximum platelet aggregation response to I-BOP ( P < .001 ) at 4 weeks and returned to baseline at 8 weeks . The EC50 values were not significantly changed . Platelet TXA2 receptor density was positively correlated ( r = .56 , P < .001 , n = 32 measurements ) with pretreatment ( endogenous ) plasma testosterone levels ( range , 215 to 883 ng/dL ) but not Kd . CONCLUSIONS Testosterone regulates the expression of platelet TXA2 receptors in humans . This may contribute to the thrombogenicity of and rogenic steroids Endogenous testosterone and estradiol are thought to be cardio-protective in men . We wanted to determine the effects of 2 different anti- and rogen therapies on arterial stiffness as one suppresses ( goserelin -- a gonadotrophin-releasing hormone analog ) while the other increases ( bicalutamide -- an and rogen receptor blocker ) both testosterone and estradiol . We conducted a r and omized trial on 43 men ( mean age , 71.2 + /- 6.2 years ) with localized prostate cancer . They received either goserelin or bicalutamide for 24 weeks . Carotid-femoral ( C-F ) and carotid-radial ( C-R ) pulse wave velocities ( PWVs ) were measured . Twenty age- and disease-matched men with prostate cancer on no active treatment were studied in a similar manner . After 12 weeks of goserelin , radial artery PWV increased significantly from baseline and a nonsignificant increase was observed in femoral PWV ( change from baseline radial : + 1.4 m/s , P = .002 , femoral : + 0.9 m/s , P = .127 ) Both PWV measures increased significantly with bicalutamide ( change from baseline radial : + 0.8 , femoral : + 0.9 m/s , P < or= .049 ) . PWV increased further after 24 weeks with goserelin ( change from baseline radial : + 1.7 , femoral : + 1.3 m/s , P < or= .049 for both ) but not bicalutamide ( change from baseline radial : + 0.4 , femoral : + 0.4 m/s , P not significant [ NS ] ) ; however , comparison of changes between the 2 drugs were not significantly different at either 12 or 24 weeks ( P > or= .967 at 12 weeks and P > or= .07 at 24 weeks ) . The untreated men studied in parallel showed no changes at 12 or 24 weeks in either PWV measure .  Anti- and rogen treatment in men might increase large artery stiffness , an adverse cardiovascular risk factor ; however , the effect was not maintained with testosterone receptor blockade , in the longer term , but tended to be sustained with suppression therapy . This could relate to the different sex hormone effects of the 2 therapies 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 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 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 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 Background —Despite diffuse effects of sex hormones on the cardiovascular system , few prospect i ve studies have examined the relationship of plasma and rogens and estrogens with risk of cardiovascular disease ( CVD ) in postmenopausal women . Methods and Results —A nested case-control study was performed among women in the Women ’s Health Study . Two hundred women who developed CVD were matched 1:1 by age , smoking , and postmenopausal hormone therapy ( HT ) to controls who remained free of CVD . We measured testosterone , estradiol , and sex hormone binding globulin ( SHBG ) levels and calculated free and rogen index ( FAI ) , free estradiol index , and the FAI/free estradiol index ratio .  Results were stratified by HT use . Among HT nonusers , cases had significantly higher and rogen profiles ( higher median FAI and lower SHBG levels ) than controls . After adjustment for age , smoking , use of aspirin , vitamin E , and alcohol , family history of myocardial infa rct ion , and physical activity , nonusers in the lowest SHBG quartile had an OR of 2.25 ( 95 % CI , 1.03 to 4.91 ) for CVD , and there were significant trends across FAI quartiles ( P for trend=0.03 ) . Additional adjustment for body mass index , hypertension , diabetes , and elevated cholesterol eliminated associations with SHBG and FAI . Among women using HT , no significant differences in hormones or SHBG were observed among women who developed CVD and controls . Conclusions —Among HT nonusers , lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events , but this was not independent of body mass index and other cardiovascular risk factors . Estradiol levels were not associated with risk of CVD in  HT  users or nonusers 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 Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population OBJECTIVE To assess the efficacy and safety of a 300 mug/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy . METHODS Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week , multicenter , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive placebo or the testosterone patch twice weekly . The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity , measured by the Sexual Activity Log . Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale . Hormone levels , adverse events , and clinical laboratory measures were review ed . RESULTS Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks ( mean change from baseline , 1.56 compared with 0.73 episodes per 4 weeks , P = .001 ) . Treatment with the testosterone patch also significantly improved sexual desire ( mean change , 10.57 compared with 4.29 , P < .001 ) and decreased personal distress ( P = .009 ) . Serum free , total , and bioavailable testosterone concentrations increased from baseline . Overall , adverse events were similar in both groups ( P > .05 ) . The incidence of and rogenic adverse events was higher in the testosterone group ; most and rogenic adverse events were mild . CONCLUSION In surgically menopausal women with hypoactive sexual desire disorder , a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire , while decreasing personal distress , and was well tolerated through up to 24 weeks of use In the study reported here , we investigated the effect of and rogens on recruitment of resting , primordial follicles into the actively growing pool . Healthy , r and om-cycling female rhesus monkeys were treated with testosterone , dihydrotestosterone ( DHT ) , or vehicle for 3 - 10 days , after which ovaries were collected for histological analysis . The first stage of follicle growth is the formation of the primary follicle , consisting of an oocyte surrounded by a single layer of cuboidal granulosa cells . The number of primary follicles was significantly increased over time in testosterone-treated animals . In situ hybridization showed that and rogen treatment result ed in an increase to 3-fold in insulin-like growth factor I ( IGF-I ) and to 5-fold in IGF-I receptor mRNA in primordial follicle oocytes . DHT effects were comparable to those of testosterone , showing that these are and rogen receptor-mediated phenomena . These data show that and rogens promote initiation of primordial follicle growth and implicate oocyte-derived IGF-I in this activation process BACKGROUND Postmenopausal hormone therapy has been examined extensively in relation to cardiovascular disease . However , research relating serum levels of sex hormones to cardiovascular disease is sparse , and the results are inconclusive . METHODS We measured sex hormones in longitudinally collected sample s of 180 postmenopausal women , 91 r and omized to 17beta-estradiol and 89 to placebo , in the Estrogen in the Prevention of Atherosclerosis Trial . Repeated measures of sex hormone levels were tested for an association with carotid artery intima-media thickness ( CIMT ) , which was also assessed longitudinally over 2 yr . RESULTS In all women , changes in serum estrone ( P = 0.02 ) , total estradiol ( P = 0.01 ) , free estradiol ( P = 0.02 ) , and SHBG ( P = 0.005 ) were significantly inversely associated with CIMT progression , controlling for age and body mass index . All the estrogen compounds and SHBG were significantly inversely related with low-density lipoprotein cholesterol and positively associated with high-density lipoprotein cholesterol ( all P < 0.0001 ) , whereas free testosterone was positively related with low-density lipoprotein cholesterol and inversely associated with high-density lipoprotein cholesterol ( P < 0.003 ) . Despite an increase in serum-free estradiol with estradiol therapy , women with unchanged SHBG and free testosterone levels had an average ( se ) progression in CIMT of 8.53 ( 4.72 ) microm/yr , whereas women with increased free estradiol and SHBG and decreased free testosterone had the largest reduction in CIMT progression [ -5.45 ( 2.77 ) microm/yr ; trend P = 0.03 ] . CONCLUSION Estrogen and SHBG are associated with reduced sub clinical atherosclerosis progression in healthy postmenopausal women . These associations are partially mediated by their beneficial effects on lipids . Among women taking estradiol , the most beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free testosterone Low and rogen levels in men are associated with increased cardiovascular risk , through unclear mechanisms . We measured arterial stiffness ( ' compliance ' ) in 21 men receiving complete testosterone suppression therapy for prostate cancer , and in 25 controls .  Systemic arterial compliance ( SAC ) , which assesses proximal aortic stiffness , was calculated by simultaneous recording of aortic flow and carotid artery pressure ( the ' area method ' ) . Aorto – femoral ( A – F ) , aorto – radial ( A – R ) and femoral – dorsalis pedis ( F – DP ) pulse-wave velocities ( PWVs ) were recorded using the ' Complior ' system . SAC was significantly lower in the and rogen-depleted men compared to controls ( 0.81 ± 0.53 vs. 1.18 ± 0.43 arbitrary compliance units , p = 0.01 , mean ± SD ) . Correspondingly , their A – F PWV was higher ( 14.1 ( 10.1–21.8 ) vs. 12.4 ( 9.6–17.4 ) m/s , p = 0.03 , median ( range ) ) . Cases tended to be older ( 75 ± 7 vs. 71 ± 6 years , p = 0.07 ) , and to have higher systolic blood pressure ( 148 ± 22 vs. 143 ± 17 mmHg , p = 0.40 ) ; however , SAC was still significantly lower ( p = 0.03 ) after adjustment for age and stratification for central systolic pressure ( ≤ or > the median ) . Adjustment of A – F PWV for age and central systolic pressure reduced significance to p = 0.07 . There was no significant difference in peripheral PWVs between groups . In conclusion , testosterone suppression is associated with increased aortic stiffness , only partly explained by age and blood pressure . Loss of and rogens in men might therefore adversely affect cardiovascular risk OBJECTIVE To determine whether testosterone levels change as women with the polycystic ovary syndrome ( PCOS ) grow older . DESIGN A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20 - 25 years ago . SETTING Women with PCOS were recruited primarily from practice records between 1970 and 1990 .  Voter registration tapes and household directories were used to identify age- , race- , and neighborhood-matched controls . PARTICIPANT(S ) Eighty-four women with PCOS , 20 - 57 years of age , and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS . INTERVENTION(S ) Clinical data were collected by question naire and fasting blood sample s were obtained r and omly throughout the menstrual cycle . MAIN OUTCOME MEASURE(S ) Total and non-SHBG-bound testosterone levels . RESULT ( S ) Total and non-SHBG-bound testosterone levels were similar in women with PCOS who were 20 - 42 years of age but were reduced by approximately 50 % among women 42 - 47 years of age and remained stable in women older than 47 years of age . Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42 - 47 years of age . CONCLUSION ( S ) Hyper and rogenism partly resolves before menopause in women with PCOS . This change may explain the tendency of women with PCOS to cycle regularly as they grow older . Testosterone levels remain elevated in older women with PCOS , however , and may contribute to their increased risk for cardiovascular disease , endometrial cancer , and other diseases 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 AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels .  Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 Summary Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men . We investigated the association between  plasma testosterone and plasma insulin  in an occupational sample of 1292 healthy adult men .  Total plasma testosterone  decreased with each decade of age and insulin increased with each decade of age . In these cross-sectional data , this significant grade d inverse association between testosterone and insulin was independent of age . The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model . Adjustment for alcohol consumption , cigarette smoking and plasma glucose did not material ly alter the association . These results are the reverse of the positive association of and rogens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk . Prospect i ve studies will be necessary to determine the direction and causal nature of this association CONTEXT Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging ; however , studies demonstrating associations of low testosterone with clinical outcomes are few . OBJECTIVE The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 794 men , aged 50 - 91 ( median 73.6 ) yr who had serum testosterone measurements at baseline ( 1984 - 1987 ) and were followed for mortality through July 2004 . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone level  was measured . RESULTS During an average 11.8-yr follow-up , 538 deaths occurred . Men whose total testosterone levels were in the lowest quartile ( < 241 ng/dl ) were 40 % [ hazards ratio ( HR ) 1.40 ; 95 % confidence interval ( CI ) 1.14 - 1.71 ] more likely to die than those with higher levels , independent of age , adiposity , and lifestyle . Additional adjustment for health status markers , lipids , lipoproteins , blood pressure , glycemia , adipocytokines , and estradiol levels had minimal effect on results . The low testosterone-mortality association was also independent of the metabolic syndrome , diabetes , and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein . In cause-specific analyses , low testosterone predicted increased risk of cardiovascular ( HR 1.38 ; 95 % CI 1.02 - 1.85 ) and respiratory disease ( HR 2.29 ; 95 % CI 1.25 - 4.20 ) mortality but was not significantly related to cancer death ( HR 1.34 ; 95 % CI 0.89 - 2.00 ) . Results were similar for bioavailable testosterone . CONCLUSIONS Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr , independent of multiple risk factors and several preexisting health conditions And rogen therapy may precipitate  obstructive sleep apnea in men . Despite increasing and rogen use in older men , few studies have examined sleep and breathing . R and omized , double-blind , placebo-controlled studies examining effects of testosterone simultaneously on sleep , breathing , and function in older men are not available . Seventeen community-dwelling healthy men over the age of 60 yr were r and omized to receive three injections of i m testosterone esters at weekly intervals ( 500 mg , 250 mg , and 250 mg ) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout .  Polysomnography , anthropometry , and physical , mental , and metabolic function were assessed at baseline and after each treatment period . Testosterone treatment reduced total time slept ( approximately 1 h ) , increased the duration of hypoxemia ( approximately 5 min/night ) , and disrupted breathing during sleep ( total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour ) ( all P < 0.05 ) . Despite expected effects on body composition ( increase in total and lean mass , reduction in fat mass , P < 0.05 , bioimpedance method ) , upper airway dimensions did not change ( acoustic reflectometry ) . Driving ability ( computer simulation ) , physical activity ( accelerometry , Physical Activity Scale in the Elderly ) , quality of life ( SF36 , Functional Outcomes of Sleep Question naire ) , mood ( Profile of Mood States Question naire ) , sleepiness ( Epworth , Stanford scales ) , and insulin resistance ( homeostasis model ) also were not changed by treatment . Short-term administration of high-dose testosterone  shortens sleep and worsens sleep apnea in older men but did not alter physical , mental , or metabolic function . These changes did not appear to be due to upper airway narrowing . Further study of longer-term lower-dose and rogen therapy on sleep and breathing is needed to evaluate its safety in older men 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 PURPOSE Cure rates for localized high-risk prostate cancers ( PCa ) and some intermediate-risk PCa are frequently suboptimal with local therapy . Outcomes are improved by concomitant and rogen-deprivation therapy ( ADT ) with radiation therapy , but not by concomitant ADT with surgery . Luteinizing hormone-releasing hormone agonist ( LHRHa ; leuprolide acetate ) does not reduce serum and rogens as effectively as abiraterone acetate ( AA ) , a prodrug of abiraterone , a CYP17 inhibitor that lowers serum testosterone ( < 1 ng/dL ) and improves survival in metastatic PCa . The possibility that greater and rogen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the re assessment of neoadjuvant ADT with more robust and rogen suppression . PATIENTS AND METHODS A neoadjuvant r and omized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa ( N = 58 ) . For the first 12 weeks , patients were r and omly assigned to LHRHa versus LHRHa plus AA . After a research prostate biopsy , all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy .  RESULTS The levels of intraprostatic and rogens from 12-week prostate biopsies , including the primary end point ( dihydrotestosterone/testosterone ) , were significantly lower ( dehydroepi and rosterone , Δ(4)- and rostene-3,17-dione , dihydrotestosterone , all P < .001 ; testosterone , P < .05 ) with LHRHa plus AA compared with LHRHa alone . Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease , with residual T3- or lymph node-positive disease in the majority . CONCLUSION LHRHa plus AA treatment suppresses tissue and rogens more effectively than LHRHa alone . Intensive intratumoral and rogen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden 10 . Nair N , Oka RK , Waring LD et al. Vascular compliance versus flow-mediated dilatation : correlation with cardiovascular risk factors . Vasc Med 2005 ; 10 : 275–83 . 11 . Wilkinson IB , MacCallum H , Cockcroft JR et al. Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo . Br J Clin Pharmacol 2002 ; 53 : 189–92 . 12 . Stewart AD , Millasseau SC , Kearney MT et al. Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans . Hypertension 2003 ; 42 : 915–8 . 13 . Bulpitt CJ , Rajkumar C , Cameron JD . Vascular compliance as a measure of biological age . J Am Geriatr Soc 1999 ; 47 : 657–63 . 14 . Rossouw JE . Risks and benefits of estrogen plus progestin in healthy postmenopausal women : principal results From the Women ’s Health Initiative r and omized controlled trial . JAMA 2002 ; 288 : 321–33 . 15 . Haddad RM , Kennedy CC , Caples SM et al.  Testosterone and cardiovascular risk in men : a systematic review and meta analysis of r and omized placebo-controlled trials . Mayo Clin Proc 2007 ; 82 : 29–39 . 16 . Lane HA , Grace F , Smith JC et al. Impaired vasoreactivity in bodybuilders using and rogenic anabolic steroids . Eur J Clin Invest 2006 ; 36 : 483–8 . 17 . McCredie RJ , McCrohon JA , Turner L et al. Vascular reactivity is impaired in genetic females taking high-dose and rogens . J Am Coll Cardiol 1998 ; 32 : 1331–5 . 18 . Ong PJL , Patrizi G , Chong WCF et al. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease . Am J Cardiol 2000 ; 85 : 269–72 . 19 . Dockery F , Bulpitt CJ , Agarwal S et al. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia . Clin Sci 2003 ; 104 : 195–201 . 20 . Swartz CM , Young MA . Low serum testosterone and myocardial infa rct ion in geriatric male in patients . J Am Geriatr Soc 1987 ; 35 : 39–44 . 21 . Phillips GB , Pinkernell BH , Jing TY . The association of hypotestosteronaemia with coronary artery disease in men . Arterioscler Thromb 1994 ; 14 : 701–6 . 22 . Webb CM , Elkington AG , Kraidly MM et al. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease . Am J Cardiol 2008 ; 101 : 618–24 , Epub 2007 Dec 21 . 23 . English KM , Steeds RP , Jones TH et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina : a r and omized , double-blind , placebocontrolled study . Circulation 2000 ; 102 : 1906–11 . 24 . Ishihara F , Hiramatsu K , Shigematsu S et al. Role of adrenal and rogens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta . Cardiology 1992 ; 80 : 332–8 . 25 . Hougaku H , Fleg JL , Najjar SS et al. Relationship between and rogenic hormones and arterial stiffness , based on longitudinal hormone measurements . Am J Physiol Endocrinol Metab 2006 ; 290 : E234–42 . 26 . Perheentupa A , Huhtaniemi I. Does the and ropause exist ? Nat Clin Pract Endocrinol Metab 2007 ; 3 : 670–1 . 27 . Emmelot-Vonk MH , Verhaar HJ , Nakhai Pour HR et al. Effect of testosterone supplementation on functional mobility , cognition , and other parameters in older men : a r and omized controlled trial . JAMA 2008 ; 299 : 39–52 . 28 . Isidori AM , Giannetta E , Greco EA et al. Effects of testosterone on body composition , bone metabolism and serum lipid profile in middle-aged men : a meta- analysis . Clin Endocrinol 2005 ; 63 : 280–93 Background : Intermittent and rogen deprivation ( IAD ) for prostate cancer was studied with the objective of reducing the side effects of treatment and potentially delaying the development of hormone resistance . There also appears to be a quality of life benefit during off-treatment intervals owing to the recovery of serum testosterone levels . Methods : In this multicentre European prospect i ve r and omised phase III trial EC507 , testosterone serum concentrations were analysed in prostate cancer patients with PSA progression after radical prostatectomy . Patients were r and omised to a continuous and rogen deprivation ( CAD ) and IAD therapy using a 3-month depot with 11.25 mg leuprorelin acetate as microcapsule formulation . A complete IAD cycle comprises both a 6-month and rogen deprivation therapy plus the off-treatment time ( OTT ) . Results : Serum testosterone recovery was recorded in 109 patients during OTT in the IAD group . Testosterone recovery to baseline values was achieved in 79.3 % during the first and in 64.9 % during the second IAD cycle , respectively . Median time to testosterone normalisation was 100 days in the first and 115 days in the second cycle , respectively . No significant difference was observed up to 1000 days between IAD and CAD with regard to time to and rogen-independent progression . This is the first prospect i ve study of leuprorelin acetate 11.25 mg demonstrating normalisation of testosterone levels in the off-treatment period in patients undergoing IAD . Conclusions : The prerequisite of an IAD treatment is the testosterone recovery during off-treatment periods . In this study , in patients with PSA relapse after radical prostatectomy , a real achievement of intermittent castration with normalisation of testosterone levels during off-treatment periods could be confirmed The role of and rogens in cardiovascular disease is uncertain . We aim ed to determine the vascular effects of and rogen suppression in men with prostate cancer .  Arterial stiffness ( or ' compliance ' ) was measured in 16 men ( 71+/-9 years , mean+/-S.D. ) prior to , and 3 months after , complete and rogen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer . Fifteen control men ( 70+/-7 years ) also had arterial stiffness studies at baseline and 3 months later . Two measures of arterial stiffness were employed : systemic arterial compliance ( SAC ) was measured by simultaneous recording of aortic flow and carotid artery pressure ( ' area method ' ) , and pulse wave velocities ( PWVs ) were recorded with the ' Complior ' system . The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits . After 3 months of testosterone suppression , there was a significant fall in SAC , which was not seen in the controls [ mean change+/-S.E.M. , -0.26+/-0.09 a.c.u . ( arbitrary compliance unit ) in the cases versus + 0.06+/-0.11 in the controls ; P = 0.03 ) . Central , but not peripheral , PWVs tended to increase in the cases ( mean change+/-S.E.M. for aorto-femoral PWV , + 0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls ; P = 0.08 ) . After testosterone suppression , fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l ( mean+/-S.D. ) , total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l ; P < 0.005 for all . No significant change occurred in body-mass index , serum glucose , low-density lipoprotein cholesterol or triacylglycerol ( triglyceride ) levels . Our results indicate that loss of and rogens in men leads to an increase in aortic stiffness and serum insulin levels , and may therefore adversely affect cardiovascular risk Although the postmenopausal ovary remains an important source of testosterone ( T ) production , there is nevertheless a decline in total circulating and rogen levels with age . A role for and rogen replacement in addition to estrogens in some postmenopausal , particularly ovariectomized , women is increasingly gaining acceptance . We have compared the pharmacokinetics of two existing testosterone preparations , oral testosterone undecanoate ( TU ) and sc testosterone implants , with a new matrix transdermal delivery system for T. In study 1 , three different doses of TU ( 40 mg , two 20-mg doses 6 h apart and two 10-mg doses 6 h apart , orally ) were investigated in 10 postmenopausal women .  Median peak levels of 18 nmol/L ( range , 5.8 - 64.0 nmol/L ; 40 mg ) , 12.3 nmol/L ( range , 5.7 - 29.2 nmol/L ; 20 mg ) , and 9.7 nmol/L ( range , 7.8 - 28.7 nmol/L ; 10 mg ) were observed , but T levels varied considerably within and between subjects regardless of the dose used . In study 2 , 30 women receiving s.c . estradiol therapy were r and omized to receive either a 100-mg T implant or placebo . In the T-treated group , levels peaked at 8.9 + /- 1.7 nmol/L 1 month after insertion and then declined gradually to 2.9 + /- 0.4 nmol/L at 6 months . In study 3 , a novel matrix transdermal delivery system for T was investigated in 6 females . Estimated daily delivery rates of 840 ( TD 1 ) , 1100 ( TD2 ) , and 3000 microg ( TD3 ) T/24 h were investigated . T rose rapidly after a single application of TD 1 and TD2 and were relatively constant for the next 18 h , at which time peaks of 2.3 + /- 1.0 and 4.1 + /- 1.6 nmol/L , respectively , at 24 h were seen . T concentrations fell to baseline levels within 6 h after patch removal . When TD2 was applied for 7 days , a T level of 4.3 + /- 0.7 nmol was seen 24 h after application , falling gradually to 2.8 + /- 0.7 nmol/L by day 7 . During twice weekly application of TD2 , stable T concentrations were maintained , and all peak levels were similar ( peak level , 4.2 + /- 0.3 nmol/L 24 h post-TD application ) as were predose troughs ( 3.2 + /- 0.3 nmol ) . Twice weekly application of TD3 produced a similar pattern of T , and the mean peak and trough levels were 7.5 + /- 0.9 and 4.0 + /- 0.4 nmol/L , respectively . In conclusion , TU produced inappropriate high T levels at all doses , with wide variations between subjects , confirming that TU is unpredictably absorbed and unlikely to be satisfactory for use in women . Subcutaneous testosterone implants produce unphysiological T levels for at least 1 - 2 months . The transdermal matrix delivery system maintained relatively stable T levels within narrow ranges with little within- and between-subject variation . We conclude that such transdermal systems may be of value for and rogen therapy in postmenopausal women because they provide a highly controllable way of delivering T noninvasively and reliably , and achieve mean physiological levels not possible with existing methods 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 PURPOSE Benign prostatic hyperplasia and hypogonadism are common disorders in aging men . There is concern that and rogen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia . We examined whether combining dutasteride , which inhibits testosterone to dihydrotestosterone conversion , with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces and rogenic stimulation of the prostate compared to testosterone alone . MATERIAL S AND METHODS We conducted a double-blind , placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia , prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl ( less than 9.7 nmol/l ) . Subjects were r and omized to daily transdermal 1 % T gel plus oral placebo or dutasteride for 6 months . Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl . The primary outcomes were prostate volume measured by magnetic resonance imaging , serum prostate specific antigen and and rogen levels . RESULTS A total of 46 subjects completed all procedures . Serum testosterone increased similarly into the mid-normal range in both groups . Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group . In the testosterone plus dutasteride  group prostate volume and prostate specific antigen ( mean ± SEM ) decreased 12 % ± 2.5 % and 35 % ± 5 % , respectively , compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5 % ± 3.3 % and 19 % ± 7 % ( p = 0.03 and p = 0.008 ) , respectively , after 6 months of treatment . Prostate symptom scores improved in both groups . CONCLUSIONS Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only . Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from and rogenic stimulation during testosterone replacement in older , hypogonadal men with symptomatic benign prostatic hyperplasia Context : Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer .  Isoflavones , a class of plant estrogens , have structural similarities to estradiol . Hence , isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects . Objective : To evaluate the effect of high-dose isoflavones on self-reported quality of life ( QOL ) , cognition , lipoproteins and and rogen status in post-menopausal women . Design and subjects : Double-blind , r and omized , placebo-controlled , 12-week trial of 93 healthy , ambulatory , post-menopausal women ( mean age 56 yr ) . The study was conducted at a tertiary care center in the United States . Intervention : Participants were r and omly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo ( 20 g whole milk protein ) . Both soy and the placebo were provided in the form of a powder to be mixed with beverages . Main outcome measures : QOL was judged by the Menopause-specific Quality of Life ( MENQOL ) question naire while cognitive function was assessed with st and ard instruments . Total , free , and bioavailable testosterone , gonadotropins , SHBG , and fasting lipids were measured . Results : Eighty-four women ( 90 % ) completed the study ( active=38 , placebo=46 ) . There was a significant improvement in all 4 QOL subscales ( vasomotor , psychosexual , physical , and sexual ) among the women taking isoflavones , while no changes were seen in the placebo group . No significant changes in cognition , serum and rogens or plasma lipids were seen within any of the groups . However , at the end of the study , a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups . Conclusion : High-dose isoflavones is associated with improved QOL among women who have become menopausal recently . Hence , the timing of isoflavone supplementation with regards to the onset of menopause appears to be important . The use of isoflavones , as an alternative to estrogen therapy , may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms Polycystic ovarian syndrome ( PCOS ) is one of the most common endocrine diseases in women . This syndrome is characterized by hyper and rogenism , chronic anovulation , infertility and obesity . The association between PCOS-related hyper and rogenemia and insulin resistance is well documented in the literature . Insulin resistance and the result ing raised plasma levels of insulin are reported to be responsible for the high and rogen concentration observed in patients with PCOS . In this prospect i ve study , blood sample s for levels of testosterone ( T ) , dehydroepi and rosterone sulfate ( DHEAS ) , luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) , LH/FSH , prolactin and fasting blood sugar ( FBS ) before starting metformin administration were obtained r and omly from 40 women who were apparently obese , had PCOS and had been referred to a university hospital .  Metformin was then given at a dose of 500 mg three times a day for 8 weeks , after which time the pretreatment study was repeated . Clinical symptoms of PCOS , including acne and hirsutism score and body mass index ( BMI ) , were assessed before and after the treatment cycle . Metformin therapy result ed in a significant decrease in total testosterone levels and FBS . There was also a significant decline in BMI , length of the menstrual cycle , acne and hirsutism score . There were no significant changes in the levels of DHEAS , prolactin , FSH or LH , or in LH/FSH . The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels . In the latter group there were only significant improvements in the length of the menstrual cycle , BMI and testosterone and DHEAS levels . It is concluded that metformin therapy in subjects with PCOS results in a decrease in fasting blood sugar and testosterone levels , and leads to a significant improvement in the clinical manifestation of hyper and rogenism . These responses also related to the level of adrenal function 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 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
Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding .
Nevertheless , overall and particularly in trials not funded by the pharmaceutical industry , exogenous testosterone increased the risk of cardiovascular-related events , with corresponding implication s for the use of testosterone therapy
Background Testosterone therapy is increasingly promoted .
No r and omized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events , although very high levels of and rogens are thought to promote cardiovascular disease .