Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Treatment of hypogonadism with testosterone in patients with type 2 diabetes mellitus. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men Testosterone therapy increased muscle mass and lipid oxidation in aging men A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. The Effect of Testosterone Supplement on Insulin Sensitivity, Glucose Effectiveness, and Acute Insulin Response After Glucose Load in Male Type 2 Diabetics Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. The Sexual Effects of Testosterone Replacement in Depressed Men: Randomized, Placebo-Controlled Clinical Trial Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men.
OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes OBJECTIVE To investigate the effect of testosterone treatment on insulin resistance , glycemic control , and dyslipidemia in Asian Indian men with type 2 diabetes mellitus ( T2DM ) and hypogonadism . METHODS We conducted a double-blind , placebo-controlled , crossover study in 22 men , 25 to 50 years old , with T2DM and hypogonadism . Patients were treated with intramuscularly administered testosterone ( 200 mg every 15 days ) or placebo for 3 months in r and om order , followed by a washout period of 1 month before the alternative treatment phase . The primary outcomes were changes in fasting insulin sensitivity ( as measured by homeostasis model assessment [ HOMA ] in those patients not receiving insulin ) , fasting blood glucose , and hemoglobin A1c . The secondary outcomes were changes in fasting lipids , blood pressure , body mass index , waist circumference , waist-to-hip ratio , and and rogen deficiency symptoms . Statistical analysis was performed on the delta values , with the treatment effect of placebo compared with the effect of testosterone . RESULTS Treatment with testosterone did not significantly influence insulin resistance measured by the HOMA index ( mean treatment effect , 1.67 + /- 4.29 ; confidence interval , -6.91 to 10.25 ; P>.05 ) . Mean change in hemoglobin A1c ( % ) ( -1.75 + /- 5.35 ; -12.46 to 8.95 ) and fasting blood glucose ( mg/dL ) ( 20.20 + /- 67.87 ; -115.54 to 155.94 ) also did not reach statistical significance . Testosterone treatment did not affect fasting lipids , blood pressure , and anthropometric determinations significantly . CONCLUSION In this study , testosterone treatment showed a neutral effect on insulin resistance and glycemic control and failed to improve dyslipidemia , control blood pressure , or reduce visceral fat significantly in Asian Indian men with T2DM and hypogonadism OBJECTIVE Low levels of testosterone in men have been shown to be associated with type 2 diabetes , visceral adiposity , dyslipidaemia and metabolic syndrome . We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes . DESIGN This was a double-blind placebo-controlled crossover study in 24 hypogonadal men ( 10 treated with insulin ) over the age of 30 years with type 2 diabetes . METHODS Patients were treated with i.m . testosterone 200 mg every 2 weeks or placebo for 3 months in r and om order , followed by a washout period of 1 month before the alternate treatment phase . The primary outcomes were changes in fasting insulin sensitivity ( as measured by homeostatic model index ( HOMA ) in those not on insulin ) , fasting blood glucose and glycated haemoglobin . The secondary outcomes were changes in body composition , fasting lipids and blood pressure . Statistical analysis was performed on the delta values , with the treatment effect of placebo compared against the treatment effect of testosterone . RESULTS Testosterone therapy reduced the HOMA index ( -1.73 + /- 0.67 , P = 0.02 , n = 14 ) , indicating an improved fasting insulin sensitivity . Glycated haemoglobin was also reduced ( -0.37 + /- 0.17 % , P = 0.03 ) , as was the fasting blood glucose ( -1.58 + /- 0.68 mmol/l , P = 0.03 ) . Testosterone treatment result ed in a reduction in visceral adiposity as assessed by waist circumference ( -1.63 + /- 0.71 cm , P = 0.03 ) and waist/hip ratio ( -0.03 + /- 0.01 , P = 0.01 ) . Total cholesterol decreased with testosterone therapy ( -0.4 + /- 0.17 mmol/l , P = 0.03 ) but no effect on blood pressure was observed . CONCLUSIONS Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes . Improvements in glycaemic control , insulin resistance , cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment .  Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( -3.96 % ) and body fat ( -5.65 % ) ; negligible changes were found in the control group . TU significantly improved metabolic control : decrease in blood glucose values and mean glycated hemoglobin ( HbA1c ) ( from 10.4 to 8.6 % ) . TU treatment significantly improved symptoms of and rogen deficiency ( including erectile dysfunction ) , with virtually no change in the control group . There were no adverse effects on blood pressure or hematological , biochemical and lipid parameters , and no adverse events . Oral TU treatment of type 2 diabetic men with and rogen deficiency  improves glucose homeostasis and body composition ( decrease in visceral obesity ) , and improves symptoms of and rogen deficiency ( including erectile dysfunction ) . In these men , the benefit of testosterone supplementation therapy exceeds the correction of symptoms of and rogen deficiency and also includes glucose homeostasis and metabolic control 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 OBJECTIVE The objective of the study was to assess the effect of T treatment on constitutional and sexual symptoms in men with type 2 diabetes ( T2D ) . DESIGN This was a r and omized double-blind , parallel , placebo-controlled trial . SETTING The study was conducted at a tertiary referral center . PATIENTS Men aged 35 - 70 years with T2D , a hemoglobin A1c less than 8.5 % , and a total T level less than 12.0 nmol/L ( 346 ng/dL ) with mild to moderate aging male symptoms and erectile dysfunction . INTERVENTION Eighty-eight participants were r and omly assigned to 40 weeks of i m T undecanoate ( n = 45 ) or matching placebo ( n = 43 ) . MAIN OUTCOME MEASURES Constitutional symptoms using the aging male symptoms ( AMS ) score , sexual desire ( question 17 AMS score ) , and erectile function ( International Index of Erectile Function-5 ) . RESULTS T treatment did not substantially improve aging male symptoms [ mean adjusted difference ( MAD ) in change over 40 weeks across the T and placebo groups in AMS total score , -0.9 ( 95 % confidence interval [ CI ] -4.1 , 2.2 ) , P = .67 ] or sexual desire [ MAD in question 17 AMS , -0.3 ( 95 % CI -0.8 , 0.2 ) , P = .17 ] . Although compared with placebo , erectile function in men assigned to T was reduced [ MAD in International Index of Erectile Function abridged version 5 , -2.0 ( 95 % CI -3.4 , -0.6 ) , P < .02 ] , there was no significant difference between baseline and 40-week International Index of Erectile Function abridged version 5 scores if both groups were analyzed separately . At baseline , symptoms were worse in men with depression and microvascular complications but did not correlate with T levels . CONCLUSIONS In this trial , T treatment did not substantially improve constitutional or sexual symptoms in obese , aging men with T2D with mild to moderate symptoms and modest reduction in T levels typical for the vast majority of such men Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p<0.001 ) following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels  following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men  on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT  reduces dementia risk OBJECTIVE Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men . Furthermore , there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men . Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance . We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein ( CRP ) in type 2 diabetic men . DESIGN Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men . Patients were treated with testosterone ( sustanon 200 mg ) or placebo intramuscularly every 2 weeks for 3 months in r and om order followed by a washout period of 1 month before the alternate treatment phase . METHODS Leptin , adiponectin , resistin , tumour necrosis factor-alpha ( TNF-alpha ) , interleukin (IL)-6 and CRP levels were measured before and after each treatment phase . Body mass index ( BMI ) and waist circumference were also recorded . RESULTS At baseline , leptin levels significantly correlated with BMI and waist circumference . There was a significant inverse correlation between baseline IL-6 and total testosterone ( r=-0.68 ; P=0.002 ) and bioavailable testosterone levels ( r=-0.73 ; P=0.007 ) . CRP levels also correlated significantly with total testosterone levels ( r=-0.59 ; P=0.01 ) . Testosterone treatment reduced leptin ( -7141.9 + /- 1461.8 pg/ml ; P=0.0001 ) and adiponectin levels ( -2075.8 + /- 852.3 ng/ml ; P=0.02 ) . There was a significant reduction in waist circumference . No significant effects of testosterone therapy on resistin , TNF-alpha , IL-6 or CRP levels were observed . CONCLUSION Testosterone replacement treatment decreases leptin and adiponectin levels  in type 2 diabetic men . Moreover , low levels of testosterone in men are associated with pro-inflammatory profile , though testosterone treatment over 3 months had no effect on inflammatory markers Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT )  were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits The indication for testosterone therapy in aging hypogonadal men without hypothalamic , pituitary , or testicular disease remains to be eluci date d. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity , substrate metabolism , body composition , and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone . A r and omized , double-blinded , placebo-controlled study of testosterone treatment ( gel ) was done on 38 men , aged 60–78 years , with bioavailable testosterone < 7.3 nmol/l and a waist circumference > 94 cm .  Insulin-stimulated glucose disposal ( Rd ) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry . Lean body mass ( LBM ) and total fat mass ( TFM ) were measured by dual x-ray absorptiometry , and serum total testosterone was measured by t and em mass spectrometry . Bioavailable testosterone was calculated . Coefficients ( b ) represent the placebo-controlled mean effect of intervention . LBM ( b = 1.9 kg , p = 0.003 ) increased while HDL – cholesterol ( b = −0.12 mmol/l , p = 0.043 ) and TFM decreased ( b = −1.2 kg , p = 0.038 ) in the testosterone group compared to placebo . Basal lipid oxidation ( b = 5.65 mg/min/m2 , p = 0.045 ) increased and basal glucose oxidation ( b = −9.71 mg/min/m2 , p = 0.046 ) decreased in response to testosterone therapy even when corrected for changes in LBM . No significant changes in insulin-stimulated Rd was observed ( b = −0.01mg/min/m2 , p = 0.92 ) . Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels ; however , our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique Men with spinal cord injury are at an increased risk for secondary medical conditions , including metabolic disorders , accelerated musculoskeletal atrophy , and , for some , hypogonadism , a deficiency , which may further adversely affect metabolism and body composition . A prospect i ve , open label , controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury . Healthy eugonadal ( n = 11 ) and hypogonadal ( n = 11 ) out patients with chronic spinal cord injury were enrolled . Hypogonadal subjects received transdermal testosterone ( 5 or 10 mg ) daily for 12 months . Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months . The testosterone replacement therapy group increased lean tissue mass for total body ( 49.6 ± 7.6 vs. 53.1 ± 6.9 kg ; p < 0.0005 ) , trunk ( 24.1 ± 4.1 vs. 25.8 ± 3.8 kg ; p < 0.005 ) , leg ( 14.5 ± 2.7 vs. 15.8 ±2.6 kg ; p = 0.005 ) , and arm ( 7.6 ± 2.3 vs. 8.0 ± 2.2 kg ; p < 0.005 ) from baseline to month 12 . After testosterone replacement  therapy , resting energy expenditure ( 1328 ± 262 vs. 1440 ± 262 kcal/d ; p < 0.01 ) and percent predicted basal energy expenditure ( 73 ± 9 vs. 79 ± 10 % ; p < 0.05 ) were significantly increased . In conclusion , testosterone replacement therapy  significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury , findings that would be expected to influence the practice of clinical care , if confirmed . Larger , r and omized , controlled clinical trials should be performed to confirm and extend our preliminary findings Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone < 10 nmol/L or free and rogen index < 30 % ) . Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD Our underst and ing of the effect of and rogens on insulin action and glucose metabolism is incomplete . Several different models and methods have been used to study and rogen effects , with some studies indicating that higher testosterone levels are associated with increased insulin resistance . In polycystic ovary syndrome , where high testosterone levels are frequently found , affected patients have a higher risk of diabetes . In contrast , increased insulin resistance was found in both hypergonadotropic and hypogonadotropic men with hypo and rogenism , patients with Klinefelter 's syndrome and men with idiopathic gonadotropin deficiency . Insulin resistance is considered to be one of the cornerstones in the state that ultimately leads to clinical ly established type 2 diabetes mellitus . In addition , men with type 2 diabetes have relative hypogonadism . Therefore , supplementation with testosterone might play a role in improving both insulin resistance and hypogonadism . The study population consisted of 11 male patients with type 2 diabetes . Their mean age was 57.7 ± 3.41 years , the body mass index ( BMI ) was 24.4 ± 1.02 kg/m2 , and the waist-to-hip ratio ( W/H ) was 0.91 ± 0.05 . The patients were all treated with oral hypoglycemic agents . The men received and rogen injections every 3 weeks intramuscularly for 12 weeks . The injections were testosterone depot 100 mg/3 weeks . Insulin sensitivity , glucose effectiveness and area under acute insulin response were calculated from " minimal model " algorithms . There were no significant differences in the value of BMI , W/H ratios , plasma lipid concentrations , testosterone , homeostasis model assessment ( HOMA ) of insulin sensitivity , and beta-cell function , before and after supplementation of testosterone . Furthermore , the insulin sensitivity ( SI ) ( 1.04 ± 0.25 , 1.11 ± 0.36 x 10−5 min−1/pM ; p = 0.43 ) , glucose effectiveness ( EG ) ( 0.018 ± 0.003 , 0.017 ± 0.002 min−1 ; p = 0.29 ) , and acute insulin response ( AIR ) after a glucose load ( 45.7 ± 24.3 , 50.1 ± 32.5 pM ; p = 0.45 ) did not change significantly after supplementation with testosterone . In our study , there was no improvement of SI , EG , and AIR after 3 months of Testosterone Depot treatment in type 2 diabetes , but we believe that duration and dosage of the and rogen therapy might play an important role in improving insulin sensitivity . The mechanisms by which testosterone causes insulin resistance is unknown , and larger studies on and rogen treatment in type 2 diabetic patients are necessary BACKGROUND Hypogonadism and anemia are common comorbid conditions in dialysis patients .  Testosterone replacement may improve such clinical parameters as anemia , sarcopenia , and low libido . Additionally , by increasing hemoglobin levels , testosterone replacement may allow for a dose reduction in recombinant human erythropoietin ( rHuEPO ) , thereby reducing cost . METHODS This phase IV , single-center , placebo-controlled , double-blind study assessed the effect of transdermal testosterone on serum testosterone levels , rHuEPO dose required to maintain hemoglobin level , bone mineral content , lean body mass and fat content , cholesterol level , sexual function , and mood . Forty hypogonadal male hemodialysis patients who were administered rHuEPO were r and omly assigned to 100 mg of topical 1 % testosterone gel ( Testim ; Auxilium Pharmaceuticals , Norristown , PA ) or placebo , applied daily for 6 months . RESULTS Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL ( < 10.4 nmol/L ) participated in this trial . In men assigned to administration of transdermal testosterone , there was an increase beyond that in the placebo group in mean serum testosterone ( 77.1 ng/dL [ 2.7 nmol/L ] ) , dihydrotestosterone ( DHT ; 0.8 nmol/L ) , and estradiol levels ( 6.3 pg/mL [ 23.0 pmol/L ] ) and a decrease in mean serum luteinizing hormone levels ( -3.1 IU/L ) . Compared with subjects administered placebo , participants on testosterone replacement therapy did not show an appreciable change in  rHuEPO dose ( mean difference adjusted for baseline values , 12.6 U/kg/wk ; P = 0.73 ) , bone mineral density , lean body mass or fat content , cholesterol level , sexual function , or mood . CONCLUSION Daily administration of 100 mg of topical 1 % testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease . Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study . Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease OBJECTIVE To investigate the effects of oral testosterone undecanoate ( TU ) on symptoms associated with late-onset hypogonadism ( LOH ) . Design Multicenter , r and omized , double-blind , placebo-controlled . METHODS The study was performed in 14 study centers in seven European countries . Men > or = 50 years ( n=322 ) with symptoms of hypogonadism and testosterone deficiency ( calculated free testosterone < 0.26 nmol/l ) were r and omized and treated for 12 months with placebo or oral TU 80 , 160 or 240 mg/day . Primary outcome was the total score on the Aging Males ' Symptoms ( AMS ) rating scale after six months of treatment . RESULTS Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU result ed in an improved total AMS score at month 6 , but differences between groups were not statistically significant . There was greater improvement in subjects < 60 years when compared with subjects > or = 60 years ( P=0.001 ) , but baseline testosterone level had no influence on treatment response . The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 ( P=0.008 ) and 12 ( P=0.012 ) compared with placebo , but not with 80 and 240 mg/day . Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates . CONCLUSIONS In one of the largest placebo-controlled studies of testosterone therapy in LOH , oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo , except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day Symptoms of male hypogonadism such as low libido and erectile dysfunction ( ED ) respond to testosterone ( T ) replacement . In hypogonadal men with major depressive disorder ( MDD ) , the extent to which T replacement alleviates sexual symptoms of hypogonadism is not known . We conducted 6 week double-blind placebo-controlled clinical trial in men with low and low-normal T levels ( i.e. , total T ≤ 350 ng/dl ) and MDD . Men were r and omized to receive weekly intramuscular injections of either T enanthate 200 mg or sesame-seed oil ( placebo ) . The primary outcome measure was self-reported sexual functioning . We r and omized 30 patients . The mean age was 52(SD ± 8) years , mean T level 262.5(SD ± 8) ng/dl , and mean baseline Hamilton Rating Scale for Depression ( HAM-D ) score 21(SD ± 8) . At baseline , sexual function was low , with the majority reporting having had normal erectile and orgasmic functioning 0–1 time in the preceding month . All patients who received T achieved normalization of their T levels . The HAM-D scores decreased significantly in both T and placebo groups , and there were no significant between-group differences : reduction in mean HAM-D score from baseline to endpoint was 10.1 in patients who received T and 10.5 in those who received  placebo . Self-reported sexual functioning improved slightly in both groups ; a between-group difference was not detected . Both T replacement and placebo were associated with improvement in sexual function and mood , but differences between T and placebo were not distinguishable We investigated whether the and rogen type or application mode or testosterone ( T ) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men r and omly assigned to the following treatment groups : mesterolone 100 mg orally daily ( [ MES ] n = 12 ) , testosterone undecanoate 160 mg orally daily ( [ TU ] n = 13 ) , testosterone enanthate 250 mg intramuscularly every 21 days ( [ TE ] n = 15 ) , or a single subcutaneous implantation of crystalline T 1,200 mg ( [ TPEL ] n = 15 ) . The dosages were based on st and ard treatment regimens . Previous and rogen substitution was suspended for at least 3 months . Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol ( TC ) and triglyceride ( TG ) less than 200 mg/dL were included . After a screening period of 2 weeks , the study medication was taken from days 0 to 189 , with follow-up visits on days 246 and 300 . Before substitution , all men were clearly hypogonadal , with mean serum T less than 3 nmol/L in all groups . And rogen substitution led to no significant increase of serum T in the MES group , subnormal T in the TU group ( 5.7 + /- 0.3 nmol/L ) , normal T in the TE group ( 13.5 + /- 0.7 nmol/L ) , and high-normal T in the TPEL group ( 23.2 + /- 1.1 nmol/L ) . 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline . Compared with presubstitution levels , a significant increase of TC was observed in all treatment groups ( TU , 14.4 % + /- 3.0 % ; MES , 18.8 % + /- 2.5 % ; TE , 20.4 % + /- 3.0 % ; TPEL , 20.2 % + /- 2.6 % ) . Low-density lipoprotein cholesterol ( LDL-C ) also increased significantly by 34.3 % + /- 5.5 % ( TU ) , 46.4 % + /- 4.1 % ( MES ) , 65.2 % + /- 5.7 % ( TE ) , and 47.5 % + /- 4.3 % ( TPEL ) . High-density lipoprotein cholesterol ( HDL-C ) showed a significant decrease by -30.9 % + /- 2.8 % ( TU ) , -34.9 % + /- 2.5 % ( MES ) , -35.7 % + /- 2.6 % ( TE ) , and -32.5 % + /- 3.5 % ( TPEL ) . Serum TG significantly increased by 37.3 % + /- 11.3 % ( TU ) , 46.4 % + /- 10.3 % ( MES ) , 29.4 % + /- 6.5 % ( TE ) , and 22.9 % + /- 6.7 % ( TPEL ) . TU caused a smaller increase of TC than TE and TPEL , whereas the parenteral treatment modes showed a lower increase of TG . There was no correlation between serum T and lipid concentrations . Despite the return of serum T to pretreatment levels , serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation . In summary , and rogen substitution  in hypogonadal men increases TC , LDL-C , and TG and decreases HDL-C independently of the and rogen type and application made and the serum and rogen levels achieved . Due to the extended washout period for previous and rogen medication and the exclusion of men with preexisting hyperlipidemia , this investigation demonstrates more clearly than previous studies the impact of and rogen effects on serum lipids and lipoproteins . It is concluded that preexisting low serum and rogens induce a " male-type " serum lipid profile , and increasing serum and rogens further within the male normal range does not exert any additional effects . The threshold appears to be above the normal female and rogen serum levels and far below the lower limit of normal serum T levels in adult men . These findings may have considerable implication s for the use of and rogens as a male contraceptive and for and rogen therapy in elderly men
The testosterone and control groups demonstrated no significant difference for other outcomes .
In conclusion , we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM .
This systematic review was aim ed at assessing the metabolic effects of testosterone replacement therapy ( TRT ) on hypogonadal men with type 2 diabetes mellitus ( T2DM ) .