title: The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Effects of testosterone supplementation in the aging male. 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 Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. 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. 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. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Therapeutic effect of andriol on serum lipids and apolipoproteins in elderly male coronary heart disease patients. The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. Randomized placebo‐controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy 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.
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 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 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 Older men , particularly those with low serum testosterone ( T ) levels , might benefit from T therapy to improve bone mineral density ( BMD ) and reduce fracture risk . Concerns exist , however , about the impact of T therapy on the prostate in older men . We hypothesized that the combination of T and finasteride ( F ) , a 5 alpha-reductase inhibitor , might increase BMD in older men without adverse effects on the prostate . Seventy men aged 65 yr or older , with a serum T less than 12.1 nmol/liter on two occasions , were r and omly assigned to receive one of three regimens for 36 months : T enanthate , 200 mg i m every 2 wk with placebo pills daily ( T-only ) ; T enanthate , 200 mg every 2 wk with 5 mg F daily ( T+F ) ; or placebo injections and pills ( placebo ) . Low BMD was not an inclusion criterion . We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry . Prostate-specific antigen ( PSA ) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate . Fifty men completed the 36-month protocol . By an intent-to-treat analysis including all men for as long as they contributed data , T therapy for 36 months increased BMD in these men at the lumbar spine [ 10.2 + /- 1.4 % ( mean percentage increase from baseline + /- SEM ; T-only ) and 9.3 + /- 1.4 % ( T+F ) vs. 1.3 + /- 1.4 % for placebo ( P < 0.001 ) ] and in the hip [ 2.7 + /- 0.7 % ( T-only ) and 2.2 + /- 0.7 % ( T+F ) vs. -0.2 + /- 0.7 % for placebo , ( P < or = 0.02 ) ] . Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip . After 6 months of therapy , urinary deoxypyridinoline ( a bone-resorption marker ) decreased significantly compared with baseline in both the T-only and T+F groups ( P < 0.001 ) but was not significantly reduced compared with the placebo group . Over 36 months , PSA increased significantly from baseline in the T-only group ( P < 0.001 ) . Prostate volume increased in all groups during the 36-month treatment period , but this increase was significantly less in the T+F group compared with both the T-only and placebo groups ( P = 0.02 ) . These results demonstrate that T therapy in older men with low serum T  increases vertebral and hip BMD over 36 months , both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men . In addition , the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy . These findings have important implication s for the prevention and treatment of osteoporosis in older men with low T levels 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 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 Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels BACKGROUND Sex hormones are known to affect cholesterol levels and vascular tone in women . The effects of testosterone on cholesterol and vascular tone in men are less well understood . Low testosterone levels have been associated with higher cholesterol levels in epidemiologic studies , but testosterone replacement has result ed in variable changes in cholesterol levels . Similarly , clinical studies suggest that testosterone may be vasodilatory , but few studies have directly evaluated the effects of testosterone on vascular tone . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - 87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone  ( 2 - 2.5 mg patches/d ) or placebo patches for 1 year . Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . RESULTS While total cholesterol , triglyceride , and low-density lipoprotein cholesterol levels did not significantly change during the year of therapy , high-density lipoprotein ( HDL ) levels ( p = .004 ) and , specifically , HDL(2 ) subfraction ( p = .02 ) decreased in men receiving testosterone supplementation . Vascular tone was measured by brachial artery reactivity in 36 men . Endothelium-dependent brachial artery reactivity did not change from baseline measurements in men receiving transdermal testosterone  ( 0.3 + /- 6.7 % to 1.6 + /- 4.6 % ; p = .58 ) or in the placebo group ( 3.2 + /- 5.5 % to 0.7 + /- 5.5 % ; p = .23 ) . CONCLUSIONS Transdermal testosterone decreased HDL(2 ) cholesterol but did not affect vascular reactivity in men older than 65 years selected for low testosterone levels . No study to date has addressed the direct relationship between testosterone replacement and cardiovascular events Testosterone ( T ) therapy in older men with low serum T levels increases lean body mass and decreases fat mass . These changes might improve physical performance and strength ; however , it has not been established whether T therapy improves functional outcome in older men . Moreover , concerns exist about the impact of T therapy on the prostate in older men . The administration of finasteride ( F ) , which partially blocks the conversion of T to the more potent and rogen , dihydrotestosterone , attenuates the impact of T replacement on prostate size and prostate-specific antigen . We hypothesized that T replacement in older , hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance , strength , and body composition . Seventy men with low serum T ( < 350 ng/dl ) , age 65 yr and older , were r and omly assigned to receive one of three regimens for 36 months : 1 ) T enanthate , 200 mg i m every 2 wk , with placebo pills daily ( T-only ) ; 2 ) T enanthate , 200 mg every 2 wk , with 5 mg F daily ( T + F ) ; or 3 ) placebo injections and pills ( placebo ) . We obtained serial measurements of timed physical performance , grip strength , lower extremity strength , body composition ( by dual-energy x-ray absorptiometry ) , fasting cholesterol profiles , and hormones .  Fifty men completed the 36-month protocol . After 36 months , T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 + /- 1.6 % ( mean + /- sem , T-only ) and 3.8 + /- 1.0 % ( T + F ) vs. -5.6 + /- 1.9 % for placebo ( P < 0.002 for both T and T + F vs. placebo ) ] and increased h and grip strength compared with baseline and placebo ( P < 0.05 ) . T therapy increased lean body mass [ 3.77 + /- 0.55 kg ( T-only ) and 3.64 + /- 0.56 kg ( T + F ) vs. -0.21 + /- 0.55 kg for placebo ( P < 0.0001 ) ] , decreased fat mass , and significantly decreased total cholesterol , low-density lipoprotein , and leptin , without affecting high-density lipoprotein , adiponectin , or fasting insulin levels . These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months , when administered alone or when combined with F , and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men We investigated the effects of 6 mo of near-physiological testosterone administration  to older men on skeletal muscle function and muscle protein metabolism .  Twelve older men ( > or = 60 yr ) with serum total testosterone concentrations < 17 nmol/l ( 480 ng/dl ) were r and omly assigned in double-blind manner to receive either placebo ( n = 5 ) or testosterone enanthate ( TE ; n = 7 ) injections . Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point . TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l . Lean body mass ( LBM ) , muscle volume , prostate size , and urinary flow were measured at baseline and at 6 mo . Protein expression of and rogen receptor ( AR ) and insulin-like growth factor I , along with muscle strength and muscle protein metabolism , were measured at baseline and at 1 and 6 mo of treatment . Hematological parameters were followed monthly throughout the study . Older men receiving  testosterone increased total and leg LBM , muscle volume , and leg and arm muscle strength after 6 mo . LBM accretion result ed from an increase in muscle protein net balance , due to a decrease in muscle protein breakdown . TE treatment increased expression of AR protein at 1 mo , but expression returned to pre-TE treatment levels by 6 mo . IGF-I protein expression increased at 1 mo and remained increased throughout TE administration . We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength 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 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 A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo  , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone .  Hypogonadism was defined as a bioavailable testosterone < 60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory .  Testosterone improved bilateral grip strength ( P < 0.05 by ANOVA ) and increased hemoglobin ( P < 0.001 by ANOVA ) . The men assigned to testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P < 0.02 ) . There were no significant changes in prostate-specific antigen or memory .  Three subjects receiving placebo and seven subjects receiving  testosterone  withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit .  Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men .  Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks Muscle wasting in older men may be related to and rogen deficiency . We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older ( age > 60 years ) men with blood testosterone levels < 14 nmol/L. Subjects ( n = 7 per group ) received testosterone enanthate 200 mg i.m . or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks . A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group . Total body mass , haemoglobin and packed cell volume also increased significantly ( p < 0.05 ) . No improvements in h and grip strength , isometric strength of knee flexors and extensors or leg extensor power were seen in either group . Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function 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 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 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 The elevated estradiol/testosterone ( E2/T ) ratio had been proved to be a risk factor for coronary heart disease ( CHD ) in elderly males and to exert an adverse effect on lipid metabolism . We conducted a r and omized cross-over study to determine the effect of And riol , a new and rogenic preparation , on plasma lipids and apolipoproteins . The results showed a significant difference in most parameters between patients receiving And riol and the control group : in the former , serum T level was elevated significantly ( P < 0.001 ) , E2 level was unchanged ( P > 0.05 ) and the E2/T ratio was reduced ( P > 0.05 ) . Blood levels of total cholesterol ( TC ) and triglyceride ( TG ) were lowered dramatically ( P < 0.001 ) and high density lipoprotein cholesterol ( HDL-ch ) was raised ( P < 0.05 ) , but apolipoprotein-AI ( APO-AI ) and B ( APO-B ) levels remained unchanged . No obvious side effect was observed in those who took And riol And rogen therapy may precipitate  obstructive sleep apnea in men . Despite increasing and rogen use in older men , few studies have examined sleep and breathing . R and omized , double-blind , placebo-controlled studies examining effects of testosterone simultaneously on sleep , breathing , and function in older men are not available . Seventeen community-dwelling healthy men over the age of 60 yr were r and omized to receive three injections of i m testosterone esters at weekly intervals ( 500 mg , 250 mg , and 250 mg ) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout .  Polysomnography , anthropometry , and physical , mental , and metabolic function were assessed at baseline and after each treatment period . Testosterone treatment reduced total time slept ( approximately 1 h ) , increased the duration of hypoxemia ( approximately 5 min/night ) , and disrupted breathing during sleep ( total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour ) ( all P < 0.05 ) . Despite expected effects on body composition ( increase in total and lean mass , reduction in fat mass , P < 0.05 , bioimpedance method ) , upper airway dimensions did not change ( acoustic reflectometry ) . Driving ability ( computer simulation ) , physical activity ( accelerometry , Physical Activity Scale in the Elderly ) , quality of life ( SF36 , Functional Outcomes of Sleep Question naire ) , mood ( Profile of Mood States Question naire ) , sleepiness ( Epworth , Stanford scales ) , and insulin resistance ( homeostasis model ) also were not changed by treatment . Short-term administration of high-dose testosterone  shortens sleep and worsens sleep apnea in older men but did not alter physical , mental , or metabolic function . These changes did not appear to be due to upper airway narrowing . Further study of longer-term lower-dose and rogen therapy on sleep and breathing is needed to evaluate its safety in older men OBJECTIVE 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 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
target: Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects .
background: OBJECTIVE To conduct a systematic review and meta- analysis of r and omized trials that assessed the effect of testosterone use on  cardiovascular events and risk factors in men with different degrees of and rogen deficiency .