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
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
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 .