Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Six months of daily treatment with vardenafil improves parameters of endothelial inflammation and of hypogonadism in male patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, prospective trial. 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. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Serum testosterone levels in diabetic men with and without erectile dysfunction A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury. The effectiveness of yoga to prevent diabetes mellitus type 2 The Effect of Testosterone Supplement on Insulin Sensitivity, Glucose Effectiveness, and Acute Insulin Response After Glucose Load in Male Type 2 Diabetics 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of 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 Type 2 diabetes mellitus ( T2DM ) is associated with endothelial dysfunction , characterized by a reduction of nitric oxide (NO)-mediated relaxation . Phosphodiesterase type 5 inhibitors ( PDE5i ) improve NO levels . The aim of the study was to investigate whether long-term , chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men . DESIGN A prospect i ve , investigator-initiated , r and omized , placebo-controlled , double-blind , clinical trial was conducted . METHODS In total , 54 male patients affected by T2DM , diagnosed within the last 5 years , and erectile dysfunction were enrolled , regardless of testosterone levels . In all , 26 and 28 patients were assigned to verum and placebo groups respectively . The study consisted of an enrollment phase , a treatment phase ( 24 weeks ) ( vardenafil/placebo 10 mg twice in a day ) and a follow-up phase ( 24 weeks ) . Parameters evaluated were as follows : International Index of Erectile Function 15 ( IIEF-15 ) , flow-mediated dilation ( FMD ) , serum interleukin 6 ( IL6 ) , endothelin 1 ( ET-1 ) , gonadotropins and testosterone ( measured by liquid chromatography/t and em mass spectrometry ) . RESULTS IIEF-15 erectile function improved during the treatment ( P<0.001 ) . At the end of the treatment both FMD ( P=0.040 ) and IL6 ( P=0.019 ) significantly improved . FMD correlated with serum testosterone levels ( R(2)=0.299 ; P<0.001 ) . Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men ( n=13 ) , without changes in gonadotropins . Chronic vardenafil treatment did not result in relevant side effects . CONCLUSION This is the first double-blind , placebo-controlled clinical trial design ed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease . Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient . Moreover , chronic vardenafil therapy improves hypogonadism in diabetic , hypogonadal men 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 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 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 Diabetes mellitus is a common chronic disease , affecting 0.5–2 % worldwide . The Massachusetts Male Aging Study reported that up to 75 % of men with diabetes have a lifetime risk of developing ED . Type 2 diabetes is associated with low total serum testosterone ( TT ) identified in several cross‐sectional studies and systemic analyses . There is a lack of consensus regarding what constitutes the lowest level of testosterone within the boundaries of normality . In this retrospective study , we sought to evaluate the effect of associated co‐morbidities on serum total testosterone ( TT ) level in men with type 2 diabetes DM , either with or without erectile dysfunction ( ED ) . Three hundred and ninety‐one patients were evaluated for erectile function  using an abridged , five‐item version of the International Index of Erectile Function‐5 . Measurements of TT , fasting lipid profile , blood sugar and glycated haemoglobin ( HbA1c ) were conducted . Penile hemodynamics was assessed using intracavernosal injection and penile duplex study .  Hypogonadism was found in 126 cases ( 33.2 % ) , and normal TT was observed in 254 ( 66.8 % ) . ED was detected in 119 cases in the hypogonadal group ( 94.4 % ) as compared to 155/254 ( 61.0 % ) in eugonadal group , P = 0.0001 . TT was lower in diabetic men with ED as compared to those with normal erectile function ( EF ) , 392.4 ± 314.9 versus 524.3 ± 140.2 ng dl−1 , respectively , P < 0.0001 . After exclusion of patients with hypertension and dyslipidaemia , 185 men were evaluated , and there was no difference in the mean TT level among men with ED 490.6 ± 498.2 ng dl−1 versus normal EF 540.6 ± 133.4 ng dl−1 although , HbA1c remained lower in men with normal erectile function . Receiver operating characteristic ( ROC ) curve of TT in men without associated co‐morbidities showed that EF was compromised at TT = 403.5 ng dl−1 or less . Sensitivity of 63.3 % and a specificity of 94.0 % were detected . At this level , ED was found in 33/38 ( 86.8 % ) men with TT 403.5 ng dl−1 , whereas ED was observed in 57/147 ( 38.8 % ) men with TT ≥ 403.5 ng dl−1 ( P < 0.0001 ) . We propose a cut‐off value of 403.5 ng dl−1 of TT blood levels as an indicator for initiation of testosterone replacement therapy in diabetic men with ED . Further prospect i ve controlled trials are recommended 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 Background : Type 2 diabetes mellitus ( T2DM ) is becoming a leading problem worldwide . Emerging reports reveal alarming evidence of increasing prevalence of T2DM that has reached p and emic levels . Despite the significant incidence , there are limited reliable data re sources and comprehensive systematic review and meta- analysis on the effects of yoga on people who are a prediabetic or high risk for developing T2DM . Objective : The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the effects of yoga on people who are prediabetes or high risk of developing T2DM . Methods : The articles enrolled in the study will be retrieved from the online data bases between 2002 and the date the search es are executed . The search es will be repeated just before the final analyses and further relevant studies for inclusion . We will conduct a bibliographic search in data bases : Medline / PubMed , Scopus , Cochrane Library , EBSCO , and IndMED using keywords including prediabetes state , high risk for diabetes , metabolic syndrome , and yoga . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . There will be no language restrictions . Ethics and dissemination : The proposed study will be based on published studies and publicly available anonymized data without directly involving human participants and therefore requires neither formal human ethical review nor approval by a human research ethics committee . We published an outline of the protocol in the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in 2018 . We plan to disseminate the findings of this systematic review and meta- analysis through publication in a peer- review ed journal and presentation at relevant conference proceedings . In addition , we believe the results of the systematic review will have implication s for policy and practice . We will prepare policymaker summary using a vali date d format , disseminate through social media and email discussion groups . Review registration number : PROSPERO registration number CRD 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 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 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 ) .