Endocrine aspects of male sexual dysfunctions. Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Effects of Oral Testosterone Treatment on Myocardial Perfusion and Vascular Function in Men With Low Plasma Testosterone and Coronary Heart Disease Correlates of low testosterone in men with chronic spinal cord injury Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression? Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status. Effect of vitamin D supplementation on testosterone levels in men. Identification of late-onset hypogonadism in middle-aged and elderly men. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up Effect of zinc supplementation on serum testosterone level in adult male sickle cell anemia subjects Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Effect of oral testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Prevalence of symptomatic androgen deficiency in men. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Effects of Testosterone Replacement in Middle-Aged Men With Dysthymia: A Randomized, Placebo-Controlled Clinical Trial Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study. Low serum testosterone and estradiol predict mortality in elderly men. The Effects of Testosterone Supplementation on Cognitive Functioning in Older Men Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. Effect of testosterone supplementation on sexual functioning in aging men: a 6-month randomized controlled trial Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Supplementation with vitamin D does not increase serum testosterone levels in healthy males. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Safety and Efficacy of Testosterone Gel 1% Augmentation in Depressed Men With Partial Response to Antidepressant Therapy Intramuscular Testosterone Supplementation to Selective Serotonin Reuptake Inhibitor in Treatment-Resistant Depressed Men: Randomized Placebo-Controlled Clinical Trial Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middle-aged men. The Effect of Testosterone Supplement on Insulin Sensitivity, Glucose Effectiveness, and Acute Insulin Response After Glucose Load in Male Type 2 Diabetics Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Adverse events associated with testosterone administration. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial Serum testosterone levels and clinical outcomes in male hemodialysis patients. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men Exercise training causes a partial improvement through increasing testosterone and eNOS for erectile function in middle-aged rats Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease.
INTRODUCTION Endocrine disorders may adversely affect men 's sexual function . AIM To provide recommendations based on best evidence for diagnosis and treatment of endocrine-related male sexual dysfunctions .  METHODS The Endocrine Aspects of Male Sexual Dysfunctions Committee , including 11 members from eight countries and four continents , collaborated with the Endocrine subcommittee of the St and ards Committee of the International Society for Sexual Medicine . Medical literature was review ed in detail , followed by extensive internal committee discussion over 2 years , then public presentation and discussion with the other experts before finalizing the report . MAIN OUTCOME MEASURE Recommendations based on grading of evidence -base medical literature and interactive discussion . RESULTS From animal studies , it is derived that testosterone modulates mechanisms involved in erectile machinery , including expression of enzymes that both initiate and terminate erection . In addition , testosterone is essential for sexual motivation . Whether these findings could be extrapolated to human erections is unclear . Testosterone plays a broad role in men 's overall health . Recent studies have established strong associations between low testosterone and metabolic and cardiovascular imbalances . In some studies , low testosterone decreased longevity ; however , longitudinal studies do not support the predictive value of low testosterone for further cardiovascular events . The article proposes a st and ardized process for diagnosis and treatment of endocrine-related male sexual dysfunctions , updating the knowledge on testosterone and prostate safety . There is no compelling evidence that testosterone treatment causes prostate cancer or its progression in men without severe testosterone deficiency ( TD ) . The possible roles of prolactin and thyroid hormones are also examined . CONCLUSIONS Men with erectile dysfunction , hypoactive sexual desire and retarded ejaculation  , as well as those with visceral obesity and metabolic diseases , should be screened for TD and treated . Prospect i ve interventional studies are required before screening for TD in more conditions , including cardiovascular diseases , and considering correction as preventive medicine as much data suggests In a single-blind , placebo-controlled study , the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate ( And riol ® ) on the quality of life of men with testosterone deficiency were evaluated . The subjects included ten men with primary hypogonadism and 29 with and ropause with sexual dysfunction as the most common problem . The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Question naire for and rogen deficiency in aging males ( ADAM ) . Digital rectal examination ( DRE ) was performed and serum testosterone , prostate-specific antigen ( PSA ) and liver profile were monitored . Testosterone undecanoate treatment ( n = 33 ) significantly improved sexual dysfunction and symptom scores of metabolic , cardiopulmonary , musculo-skeletal and gastrointestinal functions compared to baseline and to placebo ( n = 6 ) . ADAM score also significantly improved after 3 months of treatment . Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group . In the placebo group , no significant changes compared to baseline were found for testosterone levels and QoL question naires . No abnormal findings were detected on DRE or laboratory findings in either group . Adverse events , such as gastrointestinal problems and fatigue , were mild and self-limiting . It is concluded that and rogen supplement therapy with oral testosterone undecanoate ( And riol ) restores the quality of life through improvement of general body functions in men with testosterone deficiency 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 Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow . Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease . However , the effects on myocardial perfusion are unknown . Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone . Twenty-two men ( mean age 57 ± 9 [ SD ] years ) were r and omly assigned to oral testosterone undecanoate ( TU ; 80 mg twice daily ) or placebo in a crossover study design . After each 8-week period , subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance , pulse-wave analysis , and endothelial function measurements using radial artery tonometry , blood sampling , anthropomorphic measurements , and quality -of-life assessment . Although no difference was found in global myocardial perfusion after TU compared with placebo , myocardium supplied by unobstructed coronary arteries showed increased perfusion ( 1.83 ± 0.9 vs 1.52 ± 0.65 ; p = 0.037 ) . TU decreased basal radial and aortic augmentation indexes ( p = 0.03 and p = 0.02 , respectively ) , indicating decreased arterial stiffness , but there was no effect on endothelial function . TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference , but had no effect on hemostatic factors , quality of life , and angina symptoms . In conclusion , oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries , in line with previous intracoronary findings . The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia Although high rates of serum testosterone deficiency have been reported in men with spinal cord injury ( SCI ) , its determinants and attributes are not yet established . The aim of this study was to recognize , among putative determinants and attributes of and rogen deficiency , those significantly associated to low testosterone after adjustment for confounders recognizable in men with chronic SCI . A biochemical and rogen deficiency ( total testosterone < 300 ng/dL ) was exhibited by 18 of 51 patients ( 35.3 % ) . Significant correlates of testosterone levels were as follows : weekly leisure time physical activity ( LTPA )  explored by the LTPA Question naire for people with SCI , body mass index ( BMI ) , homeostatic model assessment of insulin resistance ( HOMA‐IR ) , triglycerides and sexual symptoms , explored by the aging males ' symptom ( AMS ) question naire . At the multiple linear regression analysis , among putative determinants of low testosterone , only weekly LTPA and BMI exhibited a significant association with testosterone levels , explaining 54.2 and 9.0 % of testosterone variability respectively . At the linear regression models , among various putative attributes of and rogen deficiency , only lower sexual desire and , at a lesser extent , higher HOMA‐IR , exhibited significant associations with lower testosterone levels , after adjustment for BMI , age , comorbidities and weekly LTPA . In conclusion , poor LTPA , high BMI and low sexual desire are independent predictors of low testosterone in men with chronic SCI . This is relevant to clinical practice , as all these features are routinely assessed in rehabilitation setting s for SCI . As poor LTPA and high BMI are modifiable life‐style related risk factors , prospect i ve studies could clarify whether life‐style modification could increase the level of testosterone and improve the low sexual desire , relevant clinical attribute of low testosterone in men with SCI Abstract Symptomatic and rogen deficiency is common in patients taking opioid analgesics , as these drugs potently suppress the hypothalamic – pituitary – gonadal axis . However , the efficacy of testosterone replacement in this setting remains unclear . The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other and rogen-dependent outcomes in men with opioid-induced and rogen deficiency . We conducted a r and omized , double-blind , parallel placebo-controlled trial at an outpatient academic research center . Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain , and total testosterone levels were < 350 ng/dL. Participants were r and omly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo . Primary outcomes were changes in self-reported clinical pain and objective ly assessed pain sensitivity . Sexual function , quality of life , and body composition were also assessed . The mean age was 49 years . The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm , respectively . Of the 84 r and omized participants , 65 had follow-up data on efficacy outcomes . Compared with men assigned to the placebo arm , those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia , sexual desire , and role limitation due to emotional problems . Testosterone administration was also associated with an improvement in body composition . There were no between-group differences in changes in self-reported pain . In conclusion , in men with opioid-induced and rogen deficiency , testosterone administration improved pain sensitivity , sexual desire , body composition , and aspects of quality of life Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C , but therapy-associated underlying factors for sexual dysfunction are not well defined . To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction , we prospect ively investigated changes in free testosterone , total testosterone , dehydroepi and rosterone sulfate , prolactin , sex hormone-binding globulin , FSH and LH levels and psychometric self- assessment scores in 34 male patients treated with interferon alfa-2b ( 5 MIU three times weekly ) (n=19)+ ribavirin ( n=15 ) for 6 - 12 months .  Depression was measured by the Hospital Anxiety and Depression Scale . Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder . Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function . Depression scores increased during therapy and were also significantly associated with sexual dysfunction . However , and rogen levels displayed no significant correlation with depression . These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both and rogen reduction and increased depressive symptoms . These findings may affect care for male hepatitis C patients during interferon therapy BACKGROUND Relative and rogen deficiency in ageing males is assumed to have adverse health effects . This study assessed the effect of 12 months ' st and ard dose , oral testosterone , on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men . METHODS Testosterone undecanoate ( TU , 80 mg bid ) or placebo was administered for one year to 76 healthy men , 60 years or older , with a free testosterone index ( FTI ) of 0.3 - 0.5 and significant symptoms on a question naire design ed to evaluate and rogen deficiency ( ADAM ) . The ADAM was completed at baseline , 6 and 12 months . Hormone and safety data were collected at baseline , 1 , 3 , 6 and 12 months . RESULTS After 12 months , plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group ( P = 0.01 ) . FTI and calculated bioavailable testosterone ( cBT ) were greater in the testosterone group as compared with the placebo group ( P = 0.021 and 0.025 , respectively ) . There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU . However , there were trends toward improvements in sadness/grumpiness ( P = 0.063 ) , reduced erection strength ( P = 0.059 ) and decreased work performance symptoms ( P = 0.077 ) , particularly in men with baseline cBT levels below 3.1 nmol/l . CONCLUSIONS This study concludes that 80 mg bid oral TU does not improve overall ADAM question naire scores  in older men with low-normal gonadal status . Oral TU may preserve mood and erectile function , as assessed by this question naire , particularly in men with the lowest testosterone levels The male reproductive tract has been identified as a target tissue for vitamin D , and previous data suggest an association of 25-hydroxyvitamin D [ 25(OH)D ] with testosterone levels in men . We therefore aim ed to evaluate whether vitamin D supplementation influences testosterone levels in men . Healthy overweight men undergoing a weight reduction program who participated in a r and omized controlled trial were analyzed for testosterone levels . The entire study included 200 nondiabetic subjects , of whom 165 participants ( 54 men ) completed the trial . Participants received either 83 μg ( 3,332 IU ) vitamin D daily for 1 year ( n = 31 ) or placebo ( n = 2 3 ) . Initial 25(OH)D concentrations were in the deficiency range ( < 50 nmol/l ) and testosterone values were at the lower end of the reference range ( 9.09 - 55.28 nmol/l for males aged 20 - 49 years ) in both groups . Mean circulating 25(OH)D concentrations increased significantly by 53.5 nmol/l in the vitamin D group , but remained almost constant in the placebo group . Compared to baseline values , a significant increase in total testosterone levels ( from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l ; p < 0.001 ) , bioactive testosterone ( from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l ; p = 0.001 ) , and free testosterone levels ( from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l ; p = 0.001 ) were observed in the vitamin D supplemented group . By contrast , there was no significant change in any testosterone measure in the placebo group . Our results suggest that vitamin D supplementation might increase testosterone levels . Further r and omized controlled trials are warranted to confirm this hypothesis BACKGROUND The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept . We sought evidence -based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level . METHODS We surveyed a r and om population sample of 3369 men between the ages of 40 and 79 years at eight European centers . Using question naires , we collected data with regard to the subjects ' general , sexual , physical , and psychological health . Levels of total testosterone  were measured in morning blood sample s by mass spectrometry , and  free testosterone levels  were calculated with the use of Vermeulen 's formula . Data were r and omly split into separate training and validation sets for confirmatory analyses . RESULTS In the training set , symptoms of poor morning erection , low sexual desire , erectile dysfunction , inability to perform vigorous activity , depression , and fatigue were significantly related to the testosterone level . Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels ( ranges , 8.0 to 13.0 nmol per liter [ 2.3 to 3.7 ng per milliliter ] for total testosterone and 160 to 280 pmol per liter [ 46 to 81 pg per milliliter ] for free testosterone ) . However , only the three sexual symptoms had a syndromic association with decreased testosterone levels . An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed . These relationships were independently confirmed in the validation set , in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism . CONCLUSIONS Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter ( 3.2 ng per milliliter ) and a free testosterone level of less than 220 pmol per liter ( 64 pg per milliliter ) Introduction : The clinical significance of low to low-normal testosterone ( T ) levels in men remains debated . Aim : To analyze the effects of raising serum T on lean body mass ( LBM ) , fat mass ( FM ) , total body mass , and health-related quality -of-life ( HRQoL ) . Methods : R and omized , double-blind , placebo-controlled study . Men , aged 50–80 years , with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L , and a Aging Males ’ Symptoms ( AMS ) total score > 36 , received 6 months treatment with transdermal 1 % T gel  ( 5–7.5 mg/day ; n = 183 ) or placebo gel ( n = 179 ) , followed by 12 months open-label with T in all . Results : After 6 months , LBM increased in T- treated patients by 1.28 ± 0.15 kg ( mean ± SE ) and FM decreased by 1.16 ± 0.16 kg , with minor changes with placebo ( LBM + 0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg ; all p < 0.001 , T group vs. placebo ) . Changes were largely similar across subgroups of age , baseline total testosterone , and baseline BMI . Total HRQoL improved compared with placebo ( p < 0.05 , T group vs. placebo ) . Conclusions : Six months 1 % T gel improved body composition and HRQoL  in symptomatic men with low to low-normal T , with further improvements over the following 12 months Previously , we have documented primary testicular failure in adult male subjects with sickle cell anemia . We have also reported the occurrence of zinc deficiency and suggested that and rogen deficiency may be related to zinc deficiency in such patients . In this study , we present data with respect to the effect of oral zinc supplementation on serum testosterone levels in adult male patients with sickle cell anemia . An increase in serum testosterone , neutrophil zinc , and neutrophil alkaline phosphatase activity was observed in the zinc‐supplemented group in comparison with the group on placebo . Additionally , body weight increased and serum lactic dehydrogenase activity decreased in response to zinc supplementation . We conclude that and rogen deficiency in adult male subjects with sickle cell anemia is correctable with zinc supplementation and that the determination of neutrophil zinc and alkaline phosphatase activity in the neutrophils may be utilized as good indicators of body zinc status in such subjects OBJECTIVE One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging . In this study , we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency . DESIGN Double-blind , placebo-controlled r and omized study ( testosterone ) , and additional r and omization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency . METHODS Seventy sedentary , community dwelling men were r and omized to a 5 mg testoderm transdermal system applied daily vs placebo system , and additionally r and omized to a home-based resistance exercise program . Subjects were r and omized to Group 1 ( testosterone plus exercise ) , Group 2 ( testosterone plus no exercise ) , Group 3 ( placebo plus exercise ) , and Group 4 ( placebo plus no exercise ) . Endpoints included quality of life ( assessed by the short form-36 question naire ) and body composition ( measured by dual x-ray absorptiometry scan ) . RESULTS Serum testosterone  increased by a mean of 10.0 + /- 1.9 , 6.6 + /- 1.6 , 0.52 + /- 0.6 , and 0.5 + /- 0.6 nmol/l in Groups 1 , 2 , 3 , and 4 respectively . There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning ( P = 0.03 ) , role physical ( P = 0.01 ) , general health ( P = 0.049 ) , and social functioning ( P = 0.04 ) . There were no effects of testosterone or exercise on quality of life alone , nor in body composition parameters . CONCLUSIONS Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program . The combination of testosterone and exercise may be an important strategy in the elderly , though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well CONTEXT Serum testosterone levels decline significantly with aging . Testosterone supplementation to older men might beneficially affect the aging processes . OBJECTIVE To investigate the effect of testosterone supplementation on functional mobility , cognitive function , bone mineral density , body composition , plasma lipids , quality of life , and safety parameters in older men with low normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherl and s. INTERVENTION Participants were r and omly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months . MAIN OUTCOME MEASURES Functional mobility ( Stanford Health Assessment Question naire , timed get up and go test , isometric h and grip strength , isometric leg extensor strength ) , cognitive function ( 8 different cognitive instruments ) , bone mineral density of the hip and lumbar spine ( dual-energy x-ray absorptiometry scanning ) , body composition ( total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass ) , metabolic risk factors ( fasting plasma lipids , glucose , and insulin ) , quality of life ( Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules ) , and safety parameters ( serum prostate-specific antigen level , ultrasonographic prostate volume , International Prostate Symptom score , serum levels of creatinine , aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase , hemoglobin , and hematocrit ) . RESULTS A total of 207 men completed the study . During the study , lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength . Cognitive function and bone mineral density did not change . Insulin sensitivity improved but high-density lipoprotein cholesterol decreased ; by the end of the study , 47.8 % in the testosterone group vs 35.5 % in the placebo group had the metabolic syndrome ( P = .07 ) . Quality -of-life measures were no different except for one hormone-related quality -of-life measure that improved . No negative effects on prostate safety were detected . CONCLUSION Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N23688581 OBJECTIVES The effects of supplemental testosterone on cognition , mood and wellbeing in ageing men are unclear . This study aim ed to assess the effect of 12-months of oral testosterone supplementation on cognitive function , mood and quality of life in elderly men with low-normal gonadal status , not specifically selected for cognitive or mood defects . METHODS A st and ard oral dose ( 80 mg twice daily ) of testosterone undecanoate ( TU ) or placebo was administered for one year to 76 healthy men 60 years or older . All men had a free testosterone index ( FTI ) of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . A neuropsychological assessment including the trail making test ( part B ) , visuospatial ( VSP ) block design test , mini mental state exam ( MMSE ) , Geriatric Depression Scale ( GDS ) , a 5-point Likert and a 10-point visual analogue quality of life ( QoL ) scale , along with serum hormone measurements were obtained at baseline , 6 , and 12 months . RESULTS Although calculated bioavailable testosterone ( cBT ) and FTI were higher , and muscle mass increased after 12 months , there was no difference in scores on the trail making or VSP block tests , the MMSE , GDS or either of the QoL scales between the testosterone and placebo group . There was no relationship between baseline cBT or FTI and treatment effect for any of the outcome measures . CONCLUSIONS 12-month supplementation with oral TU does not affect scores on visuospatial tests or mood and quality of life scales in older men with low-normal gonadal status CONTEXT Despite recognition that and rogen deficiency in men should be defined according to biochemical and clinical criteria , most prevalence estimates are based on low testosterone levels alone . OBJECTIVE The objective of this study was to examine the association between symptoms of and rogen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic and rogen deficiency in men . DESIGN This study was a population -based , observational survey . PARTICIPANTS A total of 1,475 Black , Hispanic , and white men , between the ages of 30 - 79 yr , with complete data on testosterone , SHBG , and symptoms of and rogen deficiency , and who are not taking medications that impact sex steroid levels were r and omly selected from the Boston Area Community Health Survey . OUTCOME Outcomes were measured as symptomatic and rogen deficiency , defined as low total ( < 300 ng/dl ) and free ( < 5 ng/dl ) testosterone plus presence of low libido , erectile dysfunction , osteoporosis or fracture , or two or more of following symptoms : sleep disturbance , depressed mood , lethargy , or diminished physical performance . RESULTS Mean age of the sample was 47.3 + /- 12.5 yr . Approximately 24 % of subjects had total testosterone less than 300 ng/dl , and 11 % of subjects had free testosterone less than 5 ng/dl . Prevalence of symptoms were as follows : low libido ( 12 % ) , erectile dysfunction ( 16 % ) , osteoporosis/fracture ( 1 % ) , and two or more of the nonspecific symptoms ( 20 % ) . Low testosterone levels were associated with symptoms , but many men with low testosterone levels were asymptomatic ( e.g. in men 50 + yr , 47.6 % ) . Crude prevalence of symptomatic and rogen deficiency was 5.6 % ( 95 % confidence interval : 3.6 % , 8.6 % ) , and was not significantly related to race and ethnic group . Prevalence was low in men less than 70 yr ( 3.1 - 7.0 % ) and increased markedly with age to 18.4 % among 70 yr olds . Projection of these estimates to the year 2025 suggests that there will be as many as 6.5 million American men ages 30 - 79 yr with symptomatic and rogen deficiency , an increase of 38 % from 2000 population estimates . CONCLUSIONS Prevalence of symptomatic and rogen deficiency in men 30 and 79 yr of age is 5.6 % and increases substantially with age . The aging of the U.S. male population will cause a large increase in the burden of symptomatic and rogen deficiency . Future work should address the clinical significance of low testosterone levels in asymptomatic men CONTEXT There is a compelling need for therapies that prevent , defer the onset , slow the progression , or improve the symptoms of Alzheimer disease ( AD ) . OBJECTIVE To evaluate the effects of testosterone therapy on cognition , neuropsychiatric symptoms , and quality of life in male patients with mild AD and healthy elderly men . DESIGN Twenty-four-week , r and omized , double-blind , placebo-controlled , parallel-group study . SETTING Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles , San Francisco , and Irvine . PATIENTS OR OTHER PARTICIPANTS Sixteen male patients with AD and 22 healthy male control subjects . Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics . INTERVENTION Testosterone and placebo , in the form of hydroalcoholic gel ( 75 mg ) , were applied daily to the skin of the participants . MAIN OUTCOME MEASURES Instruments assessing cognitive functioning ( Alzheimer 's Disease Assessment Scale-Cognitive Subscale , California Verbal Learning Test , Block Design Subtest , Judgment of Line Orientation , Developmental Test of Visual-Motor Integration ) , neuropsychiatric symptoms ( Neuropsychiatric Inventory ) , global functioning ( Clinician 's Interview-Based Impression of Change ) , and quality of life ( Quality of Life-Alzheimer Disease Scale ) . RESULTS For the patients with AD , the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality -of-life scale ( P = .01 ) . No significant treatment group differences were detected in the cognitive scores at end of study , although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo . In the healthy control group , a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group ( P = .09 ) compared with placebo treatment . No difference between the treatment groups was detected in the remaining outcome measures . Testosterone treatment was well tolerated with few adverse effects relative to placebo . CONCLUSIONS Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD .  Testosterone had minimal effects on cognition Mid-life onset male dysthymic disorder ( DD ) seems to be a distinct clinical condition with limited therapeutic options . Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy , though this strategy has received limited systematic study . We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone ( T ) level ( i.e , screening total serum testosterone < 350 ng/dL ) . Enrolled men were r and omized to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days . The primary outcome measures were the Clinical Global Impression ( CGI ) improvement score and the 21-item Hamilton Depression Rating Scale ( HDRS ) score . Twenty-three patients were r and omized . The mean ( SD ) age of the enrolled patients was 50.6 ( 7.0 ) years and that of total testosterone level was 339 ( 93 ) ng/dL. The median duration of the current dysthymic episode was 3.6 ( 2.3 ) years , and the mean ( SD ) HDRS was 14.0 ( 2.9 ) . After the intervention , the mean HDRS score decreased significantly more in the testosterone group ( 7.46 [ 4.56 ] ) than in the placebo group ( 1.8 [ 4.13 ] , t21 = −3.07 , P = 0.006 ) . Remission , defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8 , was achieved by 7 ( 53.8 % ) of 13 in the testosterone group and 1 ( 10 % ) of 10 in the placebo group ( P = 0.03 ) . Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia OBJECTIVES To To compare testosterone undecanoate versus propionyl-L-carnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms . METHODS A total of 120 patients were r and omized into three groups . The mean patient age was 66 years ( range 60 to 74 ) . Group 1 was given testosterone undecanoate 160 mg/day , the second group was given propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day . The third group was given a placebo ( starch ) . Drugs and placebo were given for 6 months . The assessed variables were total prostate-specific antigen , prostate volume , peak systolic velocity , end-diastolic velocity , resistive index of cavernosal penile arteries , nocturnal penile tumescence , total and free testosterone , prolactin , luteinizing hormone , International Index of Erectile Function score , Depression Melancholia Scale score , fatigue scale score , and incidence of side effects . The assessment was performed at intervals before , during , and after therapy . RESULTS Testosterone and carnitines significantly improved the peak systolic velocity , end-diastolic velocity , resistive index , nocturnal penile tumescence , International Index of Erectile Function score , Depression Melancholia Scale score , and fatigue scale score . Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score . Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone ; carnitines did not . No drug significantly modified prostate-specific antigen or prolactin . Carnitines and testosterone proved effective for as long as they were administered , with suspension provoking a reversal to baseline values . Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension . Placebo administration proved ineffective . Negligible side effects emerged . CONCLUSIONS Testosterone and , especially , carnitines proved to be active drugs for the therapy of symptoms associated with male aging Although decline in sexual function is a common reason for ageing men to seek advice regarding testosterone therapy , placebo-controlled trial data have been unable to show a consistent , beneficial role for testosterone . The objective of this study was to determine the effect of testosterone therapy on sexual function in non-obese ageing men with symptoms of and rogen deficiency and low – normal serum testosterone levels . A total of 60 men aged 55 years or older in good general health with total testosterone ( TT ) levels < 15 nM , and with symptoms suggestive of and rogen deficiency , were r and omized in a double-blinded protocol to transdermal testosterone patches or placebo for 12 months  . Sexual function was assessed using the International Index of Erectile Function at weeks 0 , 26 and 52 . In men receiving testosterone TT levels increased by 30 % ( P=0.01 ) and luteinizing hormone decreased by 50 % ( P<0.001 ) . Relative to placebo , testosterone therapy improved sexual desire ( P=0.04 ) ; however other parameters of sexual function including erectile function were unaffected by the treatment . Ageing men in good general health and with symptoms of and rogen deficiency and low – normal serum testosterone levels receiving 12 months of transdermal testosterone therapy experienced , relative to placebo , improved sexual desire but no effect on other parameters of sexual function Visceral fat ( VF ) increases with the menopause and is an independent predictor of the metabolic syndrome , diabetes , and cardiovascular disease ( CVD ) in women . Little is known about how hormonal changes during the menopausal transition are related to the increase in VF . We aim ed to determine the relationship between bioavailable testosterone and VF in middle-aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors . The Study of Women 's Health Across the Nation ( SWAN ) is a longitudinal , community-based study . This report uses baseline data from a population -based longitudinal ancillary study at the Chicago site to examine the cross-sectional relationship between testosterone and computed tomography (CT)-assessed VF  in women at different stages of the menopausal transition . Included are 359 women ( 47.2 % black ) , aged 42 - 60 years , who were r and omly selected from a complete community census in which a 72 % participation rate was achieved . In multivariate models , bioavailable testosterone was associated with VF independent of age , race , percent total body fat , and other cardiovascular risk factors . Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone-binding globulin ( SHBG ) . As bioavailable testosterone was associated with VF even after adjusting for insulin resistance , this suggests that it plays an important role in regional fat distribution . Our findings may have direct implication s in explaining the effect of menopause-related testosterone predominance on VF accumulation and subsequent cardiovascular risk CONTEXT Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging , but previous studies report conflicting evidence about testosterone levels and male mortality . No large prospect i ve cohort study has determined a possible association between serum estradiol and mortality in men . OBJECTIVE The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality  in elderly men . DESIGN , SETTING , AND PARTICIPANTS We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospect i ve population -based MrOS Sweden cohort ( n = 3014 ; mean age , 75 yr ; range , 69 - 80 yr ) . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone and estradiol levels . RESULTS During a mean follow-up period of 4.5 yr , 383 deaths occurred . In multivariate hazards regression models , low levels ( within quartile 1 vs. quartiles 2 - 4 ) of both testosterone [ hazard ratio ( HR ) , 1.65 ; 95 % confidence interval ( CI ) , 1.29 - 2.12 ] and estradiol ( HR , 1.54 ; 95 % CI , 1.22 - 1.95 ) associated with mortality . A model including both hormones showed that both low testosterone ( HR , 1.46 ; 95 % CI , 1.11 - 1.92 ) and estradiol ( HR , 1.33 ; 95 % CI , 1.02 - 1.73 ) predicted mortality . Risk of death nearly doubled ( HR , 1.96 ; 95 % CI , 1.46 - 2.62 ) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2 - 4 of both hormones . CONCLUSIONS Elderly men with low serum testosterone and estradiol have increased risk of mortality , and subjects with low values of both testosterone and estradiol have the highest risk of mortality Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia . Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer ’s disease pathology . In a r and omized , placebo-controlled , crossover study of men with subjective memory complaint and low testosterone levels , we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning . Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being r and omly divided into two groups . The first group ( Group A ) received 24 weeks of testosterone treatment ( T treatment ) followed by 4 weeks washout , and then 24 weeks of placebo ( P ) ; the second group ( Group B ) received the same treatments , in reverse order ( Placebo , washout , and then T treatment ) . In group A ( TèP ) , compared to baseline , there was a modest ( 1 point ) but significant improvement in general cognitive functioning as measured by the Mini Mental State Examination ( MMSE ) following testosterone treatment . This improvement from baseline was sustained following the washout period and crossover to placebo treatment . Similar Mini Mental State Examination ( MMSE ) scores were observed when comparing testosterone treatment with placebo . In group B ( PèT ) a significant increase was observed from baseline following testosterone treatment and a trend towards an increase when compared to placebo treatment . Improvements in baseline depression scores ( assessed by Geriatric Depression Scale ) were observed following testosterone/placebo treatment in both groups , and no difference was observed when comparing testosterone with placebo treatment . Our findings indicate a modest improvement on global cognition with testosterone treatment . Larger clinical trials with a longer follow- up and with the inclusion of blood and brain imaging markers are now needed to conclusively determine the significance of testosterone treatment CONTEXT Risk factors for low testosterone and symptomatic and rogen deficiency ( AD ) may be modifiable . OBJECTIVE Our objective was to examine demographic , anthropometric , and medical correlates of low testosterone and symptomatic AD . DESIGN Data were used from the Boston Area Community Health Survey , an epidemiological study conducted from 2002 - 2005 . SETTING Data were obtained from a community-based r and om sample of racially and ethnically diverse men . PATIENTS OR OTHER PARTICIPANTS Data were available for 1822 men . MAIN OUTCOME MEASURES Multivariate logistic regression  was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) for associations of covariates with 1 ) low testosterone and 2 ) symptomatic AD . The operational definition of low testosterone was serum total testosterone less than 300 ng/dl and free testosterone less than 5 ng/dl ; symptomatic AD was defined as the additional presence of symptoms : any of low libido , erectile dysfunction , or osteoporosis or two or more of sleep disturbance , depressed mood , lethargy , or diminished physical performance . RESULTS Factors associated with low testosterone included age ( OR = 1.36 ; 95 % CI= 1.11 - 1.66 , per decade ) , low per-capita income ( $ 6000 or less per household member vs. more than $ 30,000 ; OR = 2.86 ; 95 % CI = 1.39 - 5.87 ) , and waist circumference ( per 10-cm increase ; OR = 1.75 ; 95 % CI = 1.45 - 2.12 ) . Only age ( OR = 1.36 ; 95 % CI = 1.04 - 1.77 ) , waist circumference ( OR = 1.88 ; 95 % CI = 1.44 - 2.47 ) , and health status ( OR = 0.21 ; 95 % CI = 0.05 - 0.92 , excellent vs. fair/poor ) were associated with our construct of symptomatic AD . Of all variables , waist circumference was the most important contributor in both models . CONCLUSIONS Waist circumference is a potentially modifiable risk factor for low testosterone and symptomatic AD . Manifestation of symptoms may be a consequence of generally poor health status Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function . We have conducted a double-blind , r and omized , placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level < 13.7 nmol l−1 . Participants were r and omly assigned to receive oral testosterone undecanoate or a placebo for 6 months . A total of 207 men completed the study . After treatment , there were no differences in scores on sexual function between the groups . Sub analysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies , desire of sexual contact and frequency of sexual contact , supplementation of testosterone did not result in improvement on any of these items in this group . In conclusion , the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function Objective Women with primary ovarian insufficiency ( POI ) display low and rogen levels , which could contribute to mood and behavioral symptoms observed in this condition . We examined the effects of physiologic testosterone therapy added to st and ard estrogen/progestin therapy on quality of life , self-esteem , and mood in women with POI . Methods One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month r and omized , placebo-controlled , parallel- design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy .  Quality of life , self-esteem , and mood symptoms were evaluated with st and ardized rating scales and a structured clinical interview . Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests . Results No differences in baseline characteristics , including serum hormone levels ( P > 0.05 ) , were found . Baseline mean ( SD ) Center for Epidemiologic Studies Depression Scale scores were 10.7 ( 8.6 ) and 9.2 ( 7.8 ) for testosterone and placebo , respectively ( P = 0.35 ) . After 12 months of treatment , measures of quality of life , self-esteem , and mood symptoms did not differ between treatment groups . Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo ( P < 0.001 ) . Baseline testosterone levels were not associated with either adverse or beneficial clinical effects . Conclusions A 150-&mgr;g testosterone patch achieves physiologic hormone levels in women with POI . Our findings suggest that augmentation of st and ard estrogen/progestin therapy with physiologic testosterone therapy in young women with POI neither aggravates nor improves baseline reports of quality of life or self-esteem and had minimal effects on mood . Other mechanisms might play a role in the altered mood accompanying this disorder BACKGROUND Loss of muscle mass ( sarcopenia ) leads to frailty in older men . The decline in testosterone over the life span may contribute to this muscle loss . We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period . METHODS A st and ard dose ( 80 mg twice daily ) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older . All men had a free testosterone index of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . Measurements of body composition , muscle strength , hormones , and safety parameters were obtained at 0 , 6 , and 12 months . RESULTS Lean body mass increased ( p = .0001 ) and fat mass decreased ( p = .02 ) in the testosterone as compared with the placebo-treated group . There were no significant effects on muscle strength . There was a significant increase in hematocrit ( 0.02 % ) in the testosterone-treated group ( p = .03 ) . Plasma triglycerides , total cholesterol , and low-density lipoprotein cholesterol levels were similar in both groups , but there was a decrease in high-density lipoprotein cholesterol ( -0.1 mmol/L ) at 12 months in the testosterone group as compared to the placebo group ( p = 0.026 ) . There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups . CONCLUSION Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [ 25(OH)D ] and testosterone . It is not known if this relation is causal , which in theory could be in both directions . A cross-sectional population based study was design ed with pooled data from 3 vitamin D r and omized clinical trials ( RCTs ) performed in Tromsø with weight reduction , insulin sensitivity , and depression scores as endpoints , and one  testosterone RCT in subjects with low serum testosterone ( < 11.0 nmol/l ) and with body composition as endpoint .  Serum 25(OH)D and and rogens were measured in 893 males in the cross-sectional part , at baseline and after 6 - 12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs ( n=282 ) , and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections ( at baseline and after 6 , 16 , 28 , and 40 weeks ) in the testosterone RCT ( n=37 ) . In the cross-sectional study , serum 25(OH)D was found to be a significant and positive predictor of serum testosterone . In the vitamin D RCTs , no significant effect on serum total or free testosterone levels was seen , and in the testosterone RCT no significant effect on serum 25(OH)D was seen . This was unchanged in sub-analyses in subjects with low serum 25(OH)D ( or testosterone ) levels . In conclusion , in subjects without significant vitamin D deficiency , there is no increase in serum testosterone after high dose vitamin D supplementation . Similarly , in subjects with moderately low serum testosterone levels  , substitution with testosterone does not increase serum CONTEXT Serum concentrations of gonadal hormones have been associated with various measures of well-being , but it is unclear whether their association with mood is confounded by concurrent physical morbidity . OBJECTIVE To determine whether the association between serum testosterone concentration and mood in older men is independent of physical comorbidity . DESIGN Cross-sectional study . SETTING Community of Perth , Western Australia . PARTICIPANTS A community sample of men aged 71 to 89 years . MAIN OUTCOME MEASURES We used the 15-item Geriatric Depression Scale ( GDS-15 ) to assess depressed mood . Clinical ly significant depression was defined a priori as a GDS-15 score of 7 or greater . Physical health was assessed using the weighted Charlson index and the Physical Component Summary score of the 36-Item Short Form Health Survey . RESULTS Of 3987 men included in the study , 203 ( 5.1 % ; 95 % confidence interval [ CI ] , 4.4%-5.8 % ) had depression . Participants with depression had significantly lower total and free testosterone concentrations than nondepressed men ( P < .001 for both ) . However , they were also more likely to smoke and to have low educational attainment , a body mass index categorized as obese , a Mini-Mental State Examination score less than 24 , a history of antidepressant drug treatment , and greater concurrent physical morbidity . After adjusting for these factors and for age , men with depression were 1.55 ( 95 % CI , 0.91 - 2.63 ) and 2.71 ( 95 % CI , 1.49 - 4.93 ) times more likely to have total and free testosterone concentrations , respectively , in the lowest quintile . CONCLUSIONS A free testosterone concentration in the lowest quintile is associated with a higher prevalence of depression , and this association can not be adequately explained by physical comorbidity . A r and omized controlled trial is required to determine whether the link between low free testosterone level and depression is causal because older men with depression may benefit from systematic screening of free testosterone concentration and testosterone supplementation The current study evaluates the efficacy and safety of testosterone ( T ) gel 1 % augmentation on depressive symptoms and quality of life in treatment-resistant , depressed , hypogonadal men older than 50 years of age who are receiving antidepressants . The authors hypothesized that T augmentation would improve depressive symptoms and quality of life .  Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms . Participants were continued on their antidepressant and were r and omized to receive either placebo or active T gel ( 5 g ) to be applied once a day . Participants were tested on 6 occasions : screening visit , an initial session ( pretreatment ) , at 6 and 12 weeks during the first treatment condition , and at 18 and 24 weeks during the crossover condition . The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment . However , a statistical difference between placebo and testosterone treatment phases was not demonstrated . The limitations of the study , including the chronicity and severity of patients ’ depression , variability in T levels , and a small sample size , probably influenced the ability to detect a discernable difference . Nevertheless , the study shows that T gel augmentation may be helpful in hypogonadal males with depression . ( J Geriatr Psychiatry Neurol 2005 ; 18:20 - 24 Background : Treatment-resistant depression is a persistent clinical problem . Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement , although this strategy has received limited systematic study . Objective : The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression . Method : Twenty-six healthy adult men with major depressive disorder , partial or nonresponse to 2 adequate antidepressant trials during the current episode , and currently using a selective serotonin reuptake inhibitor were r and omized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo , in addition to their existing selective serotonin reuptake inhibitor regimen , for 6 weeks . The main outcome measure was the Hamilton Rating Scale for Depression score . Results : The mean age was 46.4 ± 10.8 years ; mean total testosterone level , 417.5 ± 197 ng/dL ; mean baseline Hamilton Rating Scale for Depression score , 22.2 ± 5.2 ; and median duration of the current depressive episode , 6.3 ± 10.6 years . Hamilton Rating Scale for Depression scores decreased significantly in both testosterone ( 8.4 ) and placebo ( 7.4 ) groups . Antidepressant response , defined as a 50 % decline in Hamilton Rating Scale for Depression score , was achieved by 53.8 % ( 7/13 ) in the testosterone group and 23.1 % ( 3/13 ) in the placebo group ( P = 0.226 ) . Conclusion : Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood ; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression Testosterone undecanoate ( 160 mg/day ) or placebo was given orally in a double-blind fashion for 8 months to 23 middle-aged men without urinary tract symptoms . Testosterone was found to increase the mean prostate volume by 12 % ( P < .012 ) . The treatment suppressed the serum concentrations of sex-hormone-binding globulin and follicle stimulating hormone . The observed decrease in the mean serum concentration of luteinizing hormone was not statistically significant . The serum concentrations of prostate-specific antigen did not change as measured by two different well-vali date d immunometric assays . No changes in micturition habits or urine flow charts were reported 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 This study assessed the feasibility of a 12-week program of exercise , with and without intramuscular testosterone supplementation , in male patients with chronic heart failure ( CHF ) and low testosterone status and collected preliminary data for key health outcomes . METHODS Male patients with CHF ( n = 41 , age 67.2 years , range 51 - 84 years ) with mean ± SD testosterone levels of 10.7 ± 2.6 nmol/L ( 309 ± 76 ng/dL ) were r and omly allocated to exercise with testosterone or placebo groups . Feasibility was assessed in terms of recruitment , intervention compliance , and attrition . Outcomes included an incremental shuttle walk test , peak oxygen uptake , muscular strength , echocardiographic measures , N-terminal pro-brain natriuretic peptide , inflammatory markers , depression ( Beck Depression Inventory ) , and health-related quality of life ( Minnesota Living with Heart Failure Question naire and Medical Outcomes Study Short-Form ) . RESULTS Attrition was 30 % but with 100 % compliance to exercise and injections in patients who completed the study . Similar improvements in shuttle walk test ( 18 % vs 19 % ) , body mass ( -1.3 kg vs -1.0 kg ) , and h and grip strength ( 2.1 kg vs 2.5 kg ) from baseline were observed in both groups . The exercise with testosterone group showed improvements from baseline in peak oxygen uptake ( P < .01 ) , Beck Depression Inventory ( P < .05 ) , leg strength ( P < .05 ) , and several Medical Outcomes Study Short-Form quality of life domains ( P < .05 ) , which were generally not apparent in the exercise with placebo group . Echocardiographic measures , N-terminal pro-brain natriuretic peptide , and inflammatory markers were mostly unchanged . CONCLUSIONS This study shows for the first time that testosterone supplementation during a program of exercise rehabilitation is feasible and can positively impact on a range of key health outcomes in elderly male patients with CHF who have a low testosterone status BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone  ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p < .002 ) at 12 months in the testosterone group , whereas no change occurred in the control group . Although there was no change in estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p < .017 ) . The testosterone group had a 0.3 % gain in femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia BACKGROUND Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men . The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied . METHODS Community-dwelling men , 65 years of age or older , with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter ( 3.5 to 12.1 nmol per liter ) or a free serum testosterone level of less than 50 pg per milliliter ( 173 pmol per liter ) were r and omly assigned to receive placebo gel or testosterone gel , to be applied daily for 6 months . Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification . The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group . RESULTS A total of 209 men ( mean age , 74 years ) were enrolled at the time the trial was terminated . At baseline , there was a high prevalence of hypertension , diabetes , hyperlipidemia , and obesity among the participants . During the course of the study , the testosterone group had higher rates of cardiac , respiratory , and dermatologic events than did the placebo group . A total of 23 subjects in the testosterone group , as compared with 5 in the placebo group , had cardiovascular-related adverse events . The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period . As compared with the placebo group , the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load . CONCLUSIONS In this population of older men with limitations in mobility and a high prevalence of chronic disease , the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events . The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy . ( Clinical Trials.gov number , NCT00240981 . 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 BACKGROUND Studies linking low serum testosterone concentration to adverse clinical outcomes in hemodialysis patients have been relatively small . We investigated the role of testosterone in adverse outcomes and quality of life in an incident cohort of male Canadian hemodialysis patients . STUDY DESIGN A prospect ively design ed multicenter observational study using data from the Canadian Kidney Disease Cohort Study ( CKDCS ) . SETTING & PARTICIPANTS Male patients initiating hemodialysis therapy since February 14 , 2005 , in 3 Canadian centers serving ethnically diverse population s were studied ( N = 623 ) . PREDICTOR Serum  testosterone levels using the International Society of And rology , International Society for the Study of the Aging Male , and European Association of Urology cutoffs ( low , < 231 ng/dL ; borderline , 231 - 346 ng/dL ; normal , > 346 ng/dL ) . OUTCOMES All-cause mortality , fatal and nonfatal cardiovascular ( CV ) events , and Health Utility Index (HUI)-assessed health-related quality of life . MEASUREMENTS Participants completed a structured interview on demographics and medical history and an HUI question naire ( version 3 ) . Routine laboratory test results captured into the study data base , and serum testosterone measured within 3 months after initiation of the baseline hemodialysis session . RESULTS During a median follow-up of 20 ( range , 1 - 81 ) months , 166 ( 27 % ) died and 98 ( 20 % ) had a CV event . Mean serum testosterone level was 234.1 ± 146.1 ( SD ) ng/dL. Higher serum testosterone levels were associated with significantly decreased unadjusted risk of death ( HR per 10-ng/dL increase , 0.58 ; 95 % CI , 0.37 - 0.90 ) . There was a statistically significant trend for higher all-cause mortality with low serum testosterone levels in adjusted analyses ( P < 0.001 ) . Higher levels of log-transformed testosterone were associated with significantly higher HUI scores ( P for trend < 0.001 ) , and low levels of serum testosterone were associated significantly with lower HUI scores ( P for trend < 0.001 ) . Although there was a significant trend in the unadjusted risk of CV events among participants with low serum testosterone levels ( P < 0.001 ) , the risk was no longer significant after adjustment for age . There was no significant interaction with age and serum testosterone level tested as continuous variables ( P = 0.07 ) . LIMITATIONS A short follow-up period and serum testosterone measured on a single occasion . CONCLUSIONS Low serum testosterone concentration may be a modifiable risk factor for adverse outcomes and poor quality of life in male hemodialysis patients . This hypothesis should be tested in r and omized controlled trials OBJECTIVE Testosterone supplementation may produce antidepressant effects in men , but until recently it has required cumbersome parenteral administration . In an 8-week r and omized , placebo-controlled trial , the authors administered a testosterone transdermal gel to men aged 30 - 65 who had refractory depression and low or borderline testosterone levels . METHOD Of 56 men screened , 24 ( 42.9 % ) displayed morning serum total testosterone levels of 350 ng/dl or less ( normal range=270 - 1070 ) . Of these men , 23 entered the study . One responded to an initial 1-week single-blind placebo period , and 22 were subsequently r and omly assigned : 12 to 1 % testosterone gel , 10 g/day , and 10 to identical-appearing placebo . Each subject continued his existing antidepressant regimen . Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial . RESULTS The groups were closely matched on baseline demographic and psychiatric measures . Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo . These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale . A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory . One subject assigned to testosterone reported increased difficulty with urination , suggesting an exacerbation of benign prostatic hyperplasia ; no other subject reported adverse events apparently attributable to testosterone . CONCLUSIONS These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels BACKGROUND It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range . The objective of this study was to compare the cognitive responses of older , eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation .  DESIGN R and omized , double-blind , placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline . SETTING Community dwelling participants . PARTICIPANTS Fifty-seven healthy , eugonadal , community dwelling male volunteers , mean age 67 years ( + /-11 years ) . INTERVENTIONS Participants were r and omized to receive weekly intramuscular ( i.m . ) injections of either 50 , 100 or 300 mg T enanthate or placebo ( saline ) injection for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , weeks 3 and 6 of treatment and after 6 weeks of wash-out . MAIN OUTCOME MEASURES Performance on cognitive tests of verbal and spatial memory . RESULTS Men with moderate increases in serum T and /or its metabolites demonstrated significant improvements in verbal and spatial memory . In contrast , men with large or low increases in circulating T levels , failed to demonstrate significant changes in memory . CONCLUSION These results suggest that in healthy older men , beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels . Large or no to low increases in T levels do not appear to appreciably effect cognition A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo  , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone .  Hypogonadism was defined as a bioavailable testosterone < 60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory .  Testosterone improved bilateral grip strength ( P < 0.05 by ANOVA ) and increased hemoglobin ( P < 0.001 by ANOVA ) . The men assigned to testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P < 0.02 ) . There were no significant changes in prostate-specific antigen or memory .  Three subjects receiving placebo and seven subjects receiving  testosterone  withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit .  Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men .  Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks Objective : We examined the effects on serum sex steroids , lipids and markers of oxidative stress of supplementing the diets of healthy male volunteers with scones made with soya flour . Design : A r and omized placebo controlled cross-over trial . Setting : University Hospital of Wales . Subjects : Twenty volunteers recruited by advertisement . Interventions : Male volunteers ate three scones a day in addition to their normal diet for a period of 6 weeks . The scones were made with either wheat or soya flour ( containing 120 mg/day of isoflavones ) . Blood was analysed for sex steroids ( testosterone , dihydro-testosterone , oestradiol , oestrone , sex hormone binding globulin , albumin and the concentration of non-protein bound sex steroids were calculated ) , lipid profile ( total cholesterol , high density lipoprotein cholesterol and triglycerides ) and measures of oxidative stress ( hydroperoxides , susceptibility of LDL to oxidation with copper and myeloperoxidase ) . Results : The volunteers ' mean age was 35.6 ( s.d . 11.2 ) y.  Total serum testosterone fell in volunteers taking the soya scones ( 19.3–18.2 nmol/l ; 95 % CI 1.01 , 1.12 ; P=0.03 ) . No significant changes were seen in the concentrations of the other serum sex steroids , albumin or sex hormone binding globulin throughout the study . Significant improvements in two of the three markers of oxidative stress were seen in volunteers taking soya scones . Lag time for myeloperoxidase rose from 55.0 to 68.0 min ( 95 % CI −16.0 , −3.5 ; P=0.009 ) and the presence of hydroperoxides decreased from 2.69 to 2.34 µmol/l ( 95 % CI 0.12 , 0.71 ; P=0.009 ) . There were no changes seen in serum triglycerides or cholesterol . Conclusion : We have shown that soya supplements  reduce serum testosterone and improve markers of oxidative stress . These findings provide a putative mechanism by which soya supplements could protect against prostatic disease and atherosclerosis . Further dietary studies with clinical end points are warranted . Sponsorship : The Mason medical research foundation Purpose : Aging changes the balance of sex hormones and causes endothelial dysfunction in the penis , both of which are important determinants of erectile dysfunction ( ED ) . The purpose of this study was to evaluate whether exercise training could protect against erectile dysfunction by increasing serum testosterone and penile eNOS levels in aging rats . Methods : A total of 14 young ( 2‐month‐old ) and 14 middle‐aged ( 18‐month‐old ) Sprague Dawley rats were r and omly assigned to either untrained control ( young control , [ YC ] , middle‐aged control , [ MC ] ) or endurance exercise‐trained ( young exercise , [ YE ] , middle‐aged exercise , [ ME ] ) groups with seven rats per group . The exercise groups trained with treadmill running for 6weeks . Body composition parameters ( body weight , heart mass , liver mass , and testicular mass ) , serum sex hormone levels ( testosterone , luteinizing hormone , follicle‐stimulating hormone , and prolactin ) , endothelial function‐related parameters in the penis ( endothelial nitric oxide synthase [ eNOS ] , CD31 , alpha smooth muscle actin [ & agr;‐SMA ] ) , and maximal intracavernous pressure measure ( ICP ) and total ICP were analyzed in middle‐aged rats . Results : The middle‐aged groups showed increased body weight , as compared with the young groups , but exercise training attenuated the aging‐induced increase in body weight . The middle‐aged groups had lower testicular mass compared with the young groups , but exercise training attenuated aging‐induced decreases in testicular mass  . Exercise training  increased serum testosterone levels in both the young and middle‐aged groups . However , there were no changes in the levels of luteinizing hormone , follicle‐stimulating hormone , and prolactin among the groups . MC group showed decreased protein levels of p‐eNOS , as compared with the YC group . However , exercise training protected against aging‐induced decrease in eNOS and p‐eNOS protein levels in the penis . Interestingly , exercise training also increased protein levels of & agr;‐SMA and maximal ICP in the middle‐aged group . Conclusions : Exercise training has beneficial effects on erectile function in aged rats through increased testosterone production from the testis and strengthening of the cavernous endothelium with activation of eNOS . Therefore , exercise training may be a therapeutic modality for improving erectile dysfunction associated with aging CONTEXT Symptoms of fluid retention in GH-deficient patients during GH replacement  are greater in men than in women , suggesting that testosterone may augment or estradiol may attenuate the antinatriuretic actions of GH . The mechanisms underlying the sodium-retaining effects of GH are poorly understood . AIM The aim of this study was to investigate the effects of GH and testosterone , alone and in combination , on extracellular water ( ECW ) and the hormonal mechanisms involved . DESIGN Two separate , open-label , r and omized , two-period , crossover studies were performed ; the first compared the effects of GH alone with those of GH and testosterone , and the second compared the effects of testosterone alone with those of GH and testosterone . PARTICIPANTS Twelve hypopituitary men with GH deficiency and hypogonadism were studied . INTERVENTION During the weeks of intervention , GH ( 0.5 mg/d ) and testosterone enanthate ( 250 mg ) were administered by i m injection . OUTCOME MEASURES The outcome measures were ECW , IGF-I , plasma renin activity ( PRA ) , aldosterone ( Aldo ) , and atrial natriuretic peptide ( ANP ) . RESULTS GH treatment significantly increased ( P < 0.05 ) both IGF-I and ECW , and these changes were enhanced by cotreatment with testosterone ( P = 0.07 for both ) . PRA , Aldo , and ANP levels did not change . Testosterone treatment alone did not change the IGF-I concentration , whereas cotreatment with GH induced a marked increase . Testosterone alone increased ( P < 0.05 ) ECW , and the effect was augmented ( P < 0.01 ) by cotreatment with GH . Although PRA and ANP did not change , plasma Aldo decreased after single and combined treatments . CONCLUSION GH and testosterone exerted independent and additive effects on ECW . The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules . This is the first direct evidence that testosterone increases ECW Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels
The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive .
However , supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events , all-cause mortality , or prostatic events .
Testosterone deficiency ( TD ) may induce a series of clinical symptoms .
Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients ’ quality of life .
Given the conflicting findings across studies , this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD .