Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. Substitution therapy of hypogonadal men with transdermal testosterone over one year. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study Prostatic specific antigen in patients with hypogonadism: effect of testosterone replacement. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial Effects of testosterone replacement in hypogonadal men. A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. Interval to testosterone recovery after hormonal therapy for prostate cancer and risk of death.
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 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 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 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 Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range . Recently , a transdermal therapeutic system ( TTS ) for the delivery of testosterone was developed which , when applied to the scrotum , provides smooth serum testosterone levels . Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day . In all patients serum testosterone and dihydrotestosterone ( DHT ) determined 3 - 5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period . The DHT/testosterone ratio remained constant . In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals . In these patients serum testosterone levels in the physiological range were seen during the entire observation period , whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase . All patients in the 14-month treatment study were clinical ly well substituted and responded with good compliance . Clinical chemistry showed no abnormalities during treatment . Thus , the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months .  Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men Purpose . We performed a r and omised controlled study regarding the effects of and rogen replacement therapy ( ART ) on lower urinary tract symptoms ( LUTS ) in hypogonadal men with benign prostate hypertrophy ( BPH ) . Methods . Fifty-two patients with hypogonadism and BPH were r and omly assigned to receive testosterone ( ART group ) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group . We compared International Prostate Symptom Score ( IPSS ) , uroflowmetry data , post-voiding residual volume ( PVR ) and systemic muscle volume at baseline and 12 months after treatment . Results . Forty-six patients ( ART group , n = 23 ; control , n = 23 ) were included in the analysis . At the 12-month visit , IPSS showed a significant decrease compared with baseline in the ART group ( 15.7 ± 8.7 vs. 12.5 ± 9.5 ; p < 0.05 ) . No significant changes were observed in the control group . The ART group also showed improvement in maximum flow rate and voided volume ( p < 0.05 ) , whereas no significant improvements were observed in the controls . PVR showed no significant changes in either group . In addition , the ART group showed significant enhancement of mean muscle volume ( p < 0.05 ) , whereas no significant changes were seen in the controls . Conclusion . ART improved LUTS in hypogonadal men with mild BPH INTRODUCTION The effect of parenteral testosterone replacement therapy on prostatic specific antigen ( PSA ) level or the development or growth of prostate cancer is unclear . AIM To assess the effect of testosterone replacement on PSA level in patients with hypogonadism associated with erectile dysfunction ( ED ) . METHODS A total of 187 male patients above the age of 45 with hypogonadism associated with ED were enrolled in this study . Patients were screened for ED by the erectile function domain of the International Index of Erectile Function ( IIEF ) . Patients underwent routine laboratory investigations , plus total testosterone , and PSA assessment . Replacement treatment with parenteral testosterone every 2 - 4 weeks for 1 year was instituted .  Total testosterone and PSA serum levels were assessed every 3 months during the treatment course . RESULTS Mean age + /- SD was 62.8 + /- 11.4 . Of the patients 87.7 % were sexually active . Of the patients 10.2 % had mild , 40.6 % had moderate and 49.2 % had severe ED . Of the study population , 62.5 % had ED complaints for less than 5 years and 84.5 % had gradual onset of their complaint . The majority of the patients ( 91.4 % ) had either progressive or stationary course while the minority reported regressive course and improvement of the condition . There was a significant increase of the post-treatment testosterone level in comparison to pretreatment level ( P < 0.05 ) . No significant increase in the post-treatment PSA level in comparison to pretreatment ( P > 0.05 ) . No significant difference between pre- and post-treatment categories of PSA level ( normal , borderline , high ) in relation to the severity of ED ( P > 0.05 ) . There was no significant association between PSA level and the duration of  testosterone replacement therapy in the study population ( P > 0.05 ) . CONCLUSION The current study demonstrated that the level of PSA was not significantly changed after 1 year of testosterone replacement therapy in patients with hypogonadism associated with ED Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer .  Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) < 70 ng/dL and fatigue score > 3/10 on the Edmonton Symptom Assessment Scale were eligible .  Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted Treatment of hypogonadal men with testosterone  has been shown to ameliorate the effects of testosterone deficiency on bone , muscle , erythropoiesis , and the prostate . Most previous studies , however , have employed somewhat pharmacological doses of testosterone esters , which could result in exaggerated effects , and /or have been of relatively short duration or employed previously treated men , which could result in dampened effects . The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density , muscle mass and strength , erythropoiesis , prostate volume , energy , sexual function , and lipids in previously untreated hypogonadal men . We selected 18 men who were hypogonadal ( mean serum testosterone + /- SD , 78 + /- 77 ng/dL ; 2.7 + /- 2.7 nmol/L ) due to organic disease and had never previously been treated for hypogonadism . We treated them with testosterone transdermally for 3 yr . Sixteen men completed 12 months of the protocol , and 14 men completed 36 months . The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment . Bone mineral density of the lumbar spine ( L2-L4 ) increased by 7.7 + /- 7.6 % ( P < 0.001 ) , and that of the femoral trochanter increased by 4.0 + /- 5.4 % ( P = 0.02 ) ; both reached maximum values by 24 months . Fat-free mass increased 3.1 kg ( P = 0.004 ) , and fat-free mass of the arms and legs individually increased , principally within the first 6 months . The decrease in fat mass was not statistically significant . Strength of knee flexion and extension did not change . Hematocrit increased dramatically , from mildly anemic ( 38.0 + /- 3.0 % ) to midnormal ( 43.1 + /- 4.0 % ; P = 0.002 ) within 3 months , and remained at that level for the duration of treatment . Prostate volume also increased dramatically , from subnormal ( 12.0 + /- 6.0 mL ) before treatment to normal ( 22.4 + /- 8.4 mL ; P = 0.004 ) , principally during the first 6 months . Self-reported sense of energy ( 49 + /- 19 % to 66 + /- 24 % ; P = 0.01 ) and sexual function ( 24 + /- 20 % to 66 + /- 24 % ; P < 0.001 ) also increased , principally within the first 3 months . Lipids did not change . We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip , fat-free mass , prostate volume , erythropoiesis , energy , and sexual function . The full effect of testosterone on bone mineral density took 24 months , but the full effects on the other tissues took only 3 - 6 months . These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men 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 : 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 The pharmacokinetics , efficacy , and safety of the And roderm testosterone ( T ) transdermal system ( TTD ) and intramuscular T enanthate injections ( i.m . ) for the treatment of male hypogonadism were compared in a 24-week multicenter , r and omized , parallel-group study . Sixty-six adult hypogonadal men ( 22 - 65 years of age ) were withdrawn from prior i.m . treatment for 4 - 6 weeks and then r and omly assigned to treatment with TTD ( two 2.5-mg systems applied nightly ) or i.m . ( 200 mg injected every 2 weeks ) ; there were 33 patients per group . Twenty-six patients in the TTD group and 32 in the i.m . group completed the study .  TTD treatment produced circadian variations in the levels of total T , bioavailable T , dihydrotestosterone , and estradiol within the normal physiological ranges . i.m . treatment produced supraphysiological levels of T , bioavailable T , and estradiol ( but not dihydrotestosterone ) for several days after each injection . Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients ( range , 77 - 100 % ) than i.m . patients ( range , 19 - 84 % ) . Both treatments normalized LH levels in approximately 50 % of patients with primary hypogonadism ; however , LH levels were suppressed to the subnormal range in 31 % of i.m . patients vs. 0 % of TTD patients . Both treatments maintained sexual function ( assessed by question naire and Rigiscan ) and mood ( Beck Depression Inventory ) at the prior treatment levels . Prostate-specific antigen levels , prostate volumes , and lipid and serum chemistry parameters were comparable in both treatment groups . Transient skin irritation from the patches was reported by 60 % of the TTD patients , but caused only three patients ( 9 % ) to discontinue treatment . i.m . treatment produced local reactions in 33 % of patients and was associated with significantly more abnormal hematocrit elevations ( 43.8 % of patients ) compared with TTD treatment ( 15.4 % of patients ) . Gynecomastia resolved more frequently during TTD treatment ( 4 of 10 patients ) than with i.m . treatment ( 1 of 9 patients ) . Although both treatments seem to be efficacious for replacing T in hypogonadal men , the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over i.m . in minimizing excessive stimulation of erythropoiesis , preventing/ameliorating gynecomastia , and not over-suppressing gonadotropins 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 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 PURPOSE Although there is no evidence that testosterone therapy increases the risk of prostate cancer , there is a paucity of long-term data . We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy .  MATERIAL S AND METHODS In 3 parallel , prospect i ve , ongoing , cumulative registry studies 1,023 hypogonadal men received testosterone therapy .  Two study cohorts were treated by urologists ( since 2004 ) and 1 was treated at an academic and rology center ( since 1996 ) . Patients were treated when  total testosterone was 12.1 nmol/l or less ( 350 ng/dl ) and symptoms of hypogonadism were present . Maximum followup was 17 years ( 1996 to 2013 ) and median followup was 5 years . Mean baseline patient age in the urological setting s was 58 years and in the and rology setting it was 41 years . Patients received testosterone undecanoate injections in 12-week intervals . Pretreatment examination of the prostate and monitoring during treatment were performed . Prostate biopsies were performed according to EAU guidelines . RESULTS Numbers of positive and negative biopsies were assessed . The incidence of prostate cancer and post-prostatectomy outcomes was studied . A total of 11 patients were diagnosed with prostate cancer in the 2 urology setting s at proportions of 2.3 % and 1.5 % , respectively . The incidence per 10,000 patient-years was 54.4 and 30.7 , respectively . No prostate cancer was reported by the and rology center . Limitations are inherent in the registry design without a control group . CONCLUSIONS Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer . If guidelines for testosterone therapy are properly applied , testosterone treatment is safe in hypogonadal men PURPOSE To assess whether the risk of death is associated with the time to testosterone recovery ( TTR ) after radiotherapy ( RT ) and hormonal therapy ( HT ) for prostate cancer ( PCa ) . PATIENTS AND METHODS Between 1995 and 2001 , 206 men with localized , unfavorable-risk PCa were r and omized to receive RT or RT plus 6 months of HT . A multivariate postr and omization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors , age , Adult Comorbidity Evaluation-27 score , and the use of HT for recurrence . RESULTS Of the 102 men r and omized to receive RT and HT  , 57 ( 56 % ) had a TTR of > 2 years , and none of these men had died of PCa after a median follow-up of 7.6 years . As the TTR increased , the risk of death decreased significantly ( adjusted hazard ratio , 0.60 ; 95 % confidence interval , 0.43 - 0.84 ; p = .003 ) . A significant interaction was noted between the TTR and the comorbidity score ( p = .002 ) . The survival estimates were similar ( p = 0.17 ) across the TTR values in men with moderate to severe comorbidity ; however , these estimates increased significantly ( p < .001 ) with decreasing PCa-specific mortality ( p = .006 ) as the TTR increased in men with no or minimal comorbidity . CONCLUSION The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity
Conclusions : This meta- analysis shows that regardless of the administration method , TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points
Background : Testosterone replacement therapy ( TRT ) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome .
Urologists have been concerned about the possibility of TRT causing prostate cancer .
The aim of this study was to assess the relationship between TRT and prostate cancer .