Identification of late-onset hypogonadism in middle-aged and elderly men. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). The Pituitary-Gonadal Axis and Health in Elderly Men: A Study of Men Born in 1913 Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. Clinical Effects of Treatment for Hypogonadism in Male Adolescents with Prader-Labhart-Willi Syndrome A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease Relationship between the Saint Louis University ADAM questionnaire and sexual hormonal levels in a male outpatient population over 50 years of age. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men? The Sexual Effects of Testosterone Replacement in Depressed Men: Randomized, Placebo-Controlled Clinical Trial Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study Endogenous testosterone levels, physical performance, and fall risk in older men. Relationship Between Depressive Symptoms and Hypogonadism in Men with COPD
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 ) 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 Hypogonadism and subthreshold depression are common conditions in elderly men . The objective of this study was to examine the effect of testosterone treatment in older , hypogonadal men with subthreshold depression . METHOD A r and omized , double-blind , placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older ( N = 33 ) with screening total testosterone levels of < or= 280 ng/dL and subthreshold depression ( dysthymia or minor depression , according to DSM-IV ) . Recruitment for the study was conducted from November 2002 through May 2005 . Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks , followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel . The primary outcome measure was the change in the Hamilton Rating Scale for Depression ( HAM-D ) score from baseline to the end of the double-blind phase . Secondary outcome measures were remission of subthreshold depression ( defined a priori as a HAM-D score < or= 7 ) and changes in the Hopkins Symptom Checklist depression scale , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the short-form 16-item Quality of Life Enjoyment and Satisfaction Question naire . RESULTS At the end of the double-blind phase , testosterone-treated men had a greater reduction in HAM-D scores ( p = .024 ) and a higher remission rate of subthreshold depression ( 52.9 % vs. 18.8 % , p = .041 ) than did placebo-treated men , but there were no differences in other secondary outcome measures between groups . At the end of the open-label phase , the testosterone group had sustained improvement , the control group improved , and there were no differences between groups in any outcome measures . CONCLUSION These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism . Larger studies are needed to corroborate these findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00202462 The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases . Therefore , we determined  total and free testosterone , luteinizing hormone ( LH ) , and sex-hormone binding globulin ( SHBG )  in a cohort of r and omly selected men ( n = 659 ) at 67 years of age . These data were analyzed cross-sectionally in relation to blood glucose and serum insulin , which were measured while fasting and after an oral glucose tolerance test , in addition to plasma lipids and blood pressure . The data were also analyzed in relation to impaired glucose tolerance ( IGT ) and diabetes , which were discovered at examination or earlier diagnosis . Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics . Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values ; total testosterone and SHBG , with triglycerides ; and SHBG , with blood pressure ( from P < 0.05 to P < 0.01 ) . Men with IGT or newly diagnosed diabetes had higher BMI values ( 26.2 ± 0.31 and 27.0 ± 0.59 [ mean ± SE ] , respectively ) and waist circumference ( 99.0 ± 1.03 and 100.5 ± 1.57 ) than nondiabetic men ( BMI , 25.1 ± 0.14 ; waist circumference , 95.4 ± 0.47 ; P < 0.05 ) , indicating abdominal obesity . Such men and men with previously diagnosed diabetes had , in general , lower total and free testosterone and SHBG levels , while those for LH were not different . In multivariate analyses that included BMI , waist-to-hip ratio , total and free testosterone , and SHBG , the remaining independent predictors for the development of diabetes were low total testosterone ( P = 0.015 ) and , on the borderline , low SHBG ( P = 0.053 ) . In relation to nondiabetic men , the risk ratio for mortality , myocardial infa rct ion , and stroke increased gradually and significantly from 1.18 to 1.68 , from 1.51 to 1.78 , and from 1.72 to 2.46 in men with IGT , newly diagnosed diabetes , and previously known diabetes , respectively . It was concluded that  low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes . Moreover , low testosterone levels independently predict the risk of developing diabetes . In different degrees of expression , the diabetic state predicts strongly ( and gradually mortality from ) myocardial infa rct ion and stroke . It has been suggested that a relative hypogonadism might be a primary event , because other studies have shown that testosterone deficiency is followed by insulin resistance , which is ameliorated by testosterone substitution . The data suggest that the relative hypogonadism involved might be of both central and peripheral origin 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 Circulating testosterone ( T ) levels have behavioral and neurological effects in both human and nonhuman species . Both T concentrations and neuropsychological function decrease substantially with age in men . The purpose of this prospect i ve , longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance .  Participants were volunteers from the Baltimore Longitudinal Study of Aging , aged 50 - 91 yr at baseline T assessment . Four hundred seven men were followed for an average of 10 yr , with assessment s of multiple cognitive domains and contemporaneous determination of serum total T , SHBG , and a free T index ( FTI ) . We administered  neuropsychological tests of verbal and visual memory , mental status , visuomotor scanning and attention , verbal knowledge/ language , visuospatial ability , and depressive symptomatology .  Higher FTI was associated with better scores on visual and verbal memory , visuospatial functioning , and visuomotor scanning and a reduced rate of longitudinal decline in visual memory . Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory . No relations between total T or the FTI and measures of verbal knowledge , mental status , or depressive symptoms were observed . These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men Background : In boys with Prader-Labhart-Willi syndrome ( PWS ) , hypogonadism causes pubertal arrest and reduces pubertal muscle growth . Formerly , it was assumed that therapy with gonadal hormones accentuates behaviour abnormalities in PWS . Our aim was to assess the clinical effects of human chorionic gonadotropin ( hCG ) therapy on pubertal development , muscle mass and behaviour in adolescents with PWS . Methods : 6 peripubertal boys with PWS undergoing long-term treatment with growth hormone  were examined 6-monthly for at least 2 years before and after pubertal arrest ( 13.5 ± 0.3 years , mean ± SEM ) and the beginning of hCG therapy ( 500–1,500 IU twice weekly , intramuscularly ) . Height , weight , pubertal stage , bone age , body composition ( by dual-energy X-ray absorptiometry ) , testosterone levels and behaviour abnormalities ( obtained from parents ) were assessed . Results : Testicular volume and lean mass were reduced in pubertal boys with PWS . During hCG therapy , testosterone levels and lean mass significantly increased ( at the beginning and after 2 years of hCG therapy : 2.3 ± 0.9 and 10.7 ± 1.3 nmol/l , –3.1 ± 0.3 and –1.4 ± 0.6 SD , respectively ) , and fat mass stabilized at 38 % . The characteristically observed PWS-associated problems , mood instability , aggressiveness and difficulties in social interaction , did not deteriorate during therapy . Conclusion : In the present study , timely application of hCG to treat hypogonadism in boys with PWS  promoted virilization and normalized muscle mass without detrimental effects on behaviour . Larger studies comparing hCG therapy with testosterone replacement would be useful Men with spinal cord injury are at an increased risk for secondary medical conditions , including metabolic disorders , accelerated musculoskeletal atrophy , and , for some , hypogonadism , a deficiency , which may further adversely affect metabolism and body composition . A prospect i ve , open label , controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury . Healthy eugonadal ( n = 11 ) and hypogonadal ( n = 11 ) out patients with chronic spinal cord injury were enrolled . Hypogonadal subjects received transdermal testosterone ( 5 or 10 mg ) daily for 12 months . Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months . The testosterone replacement therapy group increased lean tissue mass for total body ( 49.6 ± 7.6 vs. 53.1 ± 6.9 kg ; p < 0.0005 ) , trunk ( 24.1 ± 4.1 vs. 25.8 ± 3.8 kg ; p < 0.005 ) , leg ( 14.5 ± 2.7 vs. 15.8 ±2.6 kg ; p = 0.005 ) , and arm ( 7.6 ± 2.3 vs. 8.0 ± 2.2 kg ; p < 0.005 ) from baseline to month 12 . After testosterone replacement  therapy , resting energy expenditure ( 1328 ± 262 vs. 1440 ± 262 kcal/d ; p < 0.01 ) and percent predicted basal energy expenditure ( 73 ± 9 vs. 79 ± 10 % ; p < 0.05 ) were significantly increased . In conclusion , testosterone replacement therapy  significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury , findings that would be expected to influence the practice of clinical care , if confirmed . Larger , r and omized , controlled clinical trials should be performed to confirm and extend our preliminary findings CONTEXT The cause of declining testosterone ( T )  in aging men and their relationships with risk factors are unclear . OBJECTIVE The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men . DESIGN This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40 - 79 yr from a prospect i ve cohort study in eight European countries . RESULTS Four predictors were associated with distinct modes of altered function : 1 ) age : lower free T ( FT ; -3.12 pmol/liter.yr , P < 0.001 ) with raised LH , suggesting impaired testicular function ; 2 ) obesity : lower total T ( TT ; -2.32 nmol/liter ) and FT ( -17.60 pmol/liter ) for body mass index ( BMI ; > or = 25 to < 30 kg/m(2 ) ) and lower TT ( -5.09 nmol/liter ) and FT ( -53.72 pmol/liter ) for BMI 30 kg/m(2 ) or greater ( P < 0.001 - 0.01 , referent : BMI < 25 kg/m(2 ) ) with unchanged/decreased LH , indicating hypothalamus/pituitary dysfunction ; 3 ) comorbidity : lower TT ( -0.80 nmol/liter , P < 0.01 ) with unchanged LH in younger men but higher LH in older men ; and 4 ) smoking : higher SHBG ( 5.96 nmol/liter , P < 0.001 ) and LH ( 0.77 U/liter , P < 0.01 ) with increased TT ( 1.31 nmol/liter , P < 0.001 ) but not FT , compatible with a re setting of T-LH-negative feedback due to elevated SHBG . CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment . These changes are differentially linked to specific risk factors . Some risk factors operate independently of but others interact with age , in contributing to the T decline . These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels . Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors . Tau protein deposition is also affected by and rogen supplementation in animals . We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition , in particular the visual-spatial domain . Thirty-six male patients with a new diagnosis of Alzheimer 's disease had their total and bioavailable testosterone levels measured . None of the patients had been on acetylcholinesterase inhibitors .  Ten of the 36 patients ( 28 % ) were deemed biochemically hypogonadal ( total testosterone < 240 ng/dl or 7 nmol/l ) . Five of the hypogonadal patients were r and omized to testosterone and five to placebo . Initial Alzheimer 's Disease Assessment Scale cognitive subscale ( ADAScog ) and Mini Mental Status Examination ( MMSE ) ranged from 31 to 19 and from 17 to 22 , respectively . The  clock drawing test ( CDT ) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities . Normal prostate-specific antigen ( PSA ) levels were essential before treatment with intramuscular testosterone , 200 mg every 2 weeks . Measurement of testosterone , complete blood count , lipids , PSA and neuropsychological cognitive tests were repeated at 3 , 6 , 9 and 12 months of treatment . In the testosterone-treated group , levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l ( p = 0.11 ) . Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l ( p = 0.10 ) . PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml ( p = 0.07 ) . ADAScog improved from a mean of 25 to 16.3 ( p = 0.02 ) ; MMSE improved from a mean of 19.4 to 23.2 ( p = 0.02 ) , CDT also improved from 2.2 to 3.2 ( p = 0.07 ) . One patient stopped treatment because of hypersexual behavior . The placebo-treated group deteriorated gradually . This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition , including visual-spatial skills in mild to moderate Alzheimer 's disease OBJECTIVES To determine the relationship between the ADAM question naire and the sexual hormonal levels in a male population older than 50 yr , and to know the predictive capacity of this question naire with regard to biochemical hypogonadism in the ageing male . METHODS A prospect i ve study was carried out on 230 Spanish men . Patients were evaluated by clinical history . The ADAM question naire and the Yesavage 's Geriatric Depression Scale were completed by each patient . Blood tests were performed including total testosterone , SHBG , free testosterone ( FT ) , dehidroepi and rosterone sulfate ( DHEA-S ) , and rostenedione , 17-beta-estradiol , FSH , LH , and prolactin . The relationship between positive ADAM question naire and age , clinical and sociodemographic background s , and hormone levels was analysed by means of uni- and multivariate tests . The capacity of the ADAM question naire to predict biochemical hypogonadism was determined with a chi-square test . RESULTS ADAM question naire ( excluding men with positive Yesavage 's Scale ) was positive in 140 patients ( 67.9 % ) . With respect to clinical background s , diabetes mellitus and age had a significant relationship with an ADAM-positive question naire . With respect to hormones , FT and DHEA-S levels were significantly lower when the ADAM question naire was positive . In the multivariate analysis , age , FT , and diabetes were independently related to an ADAM-positive question naire . Prevalence of biochemical hypogonadism ( FT<0.228 nmol/l ) was 24.6 % . The ADAM test had a sensitivity of 84.0 % and a specificity of 36.6 % to detect biochemical hypogonadism . CONCLUSIONS FT is inversely related to the ADAM-positive question naire , independently of age . The ADAM question naire is a valid test to detect hypogonadism but has low specificity To investigate ( 1 ) the effects of exogenous testosterone ( T ) on  self- and partner-reported aggression and mood  and ( 2 ) the role of trait impulsivity in the T-aggression relationship .  Thirty eugonadal men with partners were r and omized into two treatment groups to receive : ( 1 ) 200 mg i m T enanthate weekly for 8 weeks or ( 2 ) 200 mg i m sodium chloride weekly for 8 weeks . Eight hypogonadal men received 200 mg i m T enanthate biweekly for 8 weeks . All groups completed a battery of behavior measures at baseline ( Week 0 ) and at Weeks 4 and 8 . Cognitive and motor impulsivity were the only predictors of self-reported total aggression ( over and above age and T levels ) at Weeks 0 , 4 , and 8 . No significant changes in aggression or mood levels were found in the eugonadal-treated group . Significant reductions in negative mood ( tension , anger , and fatigue ) followed by an increase in vigor were found in response to T treatment in the hypogonadal group . These results demonstrate that inability to control one 's behavior when such control is required by a particular situation ( impulsivity ) was found to significantly predict levels of aggression over and above age and T level . These data do not support the hypothesis that supraphysiological levels of T ( within this range ) lead to an increase in self- and partner-reported aggression or mood disturbances . Instead , for the first time , this study has identified the high level of negative affect experienced by hypogonadal patients . These findings have implication s for T replacement therapy and male contraception The risk of MTHF in hypogonadal elderly men was investigated with a case-control model . Cases and controls were selected from males age 65 years and older residing in the 120-bed McGuire Veterans Affairs Medical Center Nursing Home Care Unit over a 5-day interval .  Historical data and  serum free testosterone ( fTe )  were available on 17 subjects with MTHF and 61 controls . When groups were compared for differences in age , race , alcohol abuse , cigarette abuse , and diseases or drugs that may be associated with MTHF , only race was significantly different . Although 25.6 % of residents were black , 100 % of MTHF subjects were white ( P = 0.004 ) . Hypogonadism was defined as a r and om fTe less than 9 pg/mL ( normal 9 to 46 pg/mL ) and was found in 21 subjects ( 26.9 % ) . Of cases with a MTHF , 58.8 % were hypogonadal compared with only 18.0 % of controls . Utilizing logistic regression , a highly significant association was found between hypogonadism and MTHF ( P = 0.008 ) , and using the odds ratio , subjects with hypogonadism were 6.5 times more likely to have a MTHF ( 95 % CI 2.0 to 20.6 ) . To adjust for race , the odds ratio was repeated excluding black subjects , and the results remained highly significant ( 4.6 , 95 % CI 1.3 to 16.2 ) . We conclude that hypogonadal elderly white men may be at increased risk for MTHF Symptoms of male hypogonadism such as low libido and erectile dysfunction ( ED ) respond to testosterone ( T ) replacement . In hypogonadal men with major depressive disorder ( MDD ) , the extent to which T replacement alleviates sexual symptoms of hypogonadism is not known . We conducted 6 week double-blind placebo-controlled clinical trial in men with low and low-normal T levels ( i.e. , total T ≤ 350 ng/dl ) and MDD . Men were r and omized to receive weekly intramuscular injections of either T enanthate 200 mg or sesame-seed oil ( placebo ) . The primary outcome measure was self-reported sexual functioning . We r and omized 30 patients . The mean age was 52(SD ± 8) years , mean T level 262.5(SD ± 8) ng/dl , and mean baseline Hamilton Rating Scale for Depression ( HAM-D ) score 21(SD ± 8) . At baseline , sexual function was low , with the majority reporting having had normal erectile and orgasmic functioning 0–1 time in the preceding month . All patients who received T achieved normalization of their T levels . The HAM-D scores decreased significantly in both T and placebo groups , and there were no significant between-group differences : reduction in mean HAM-D score from baseline to endpoint was 10.1 in patients who received T and 10.5 in those who received  placebo . Self-reported sexual functioning improved slightly in both groups ; a between-group difference was not detected . Both T replacement and placebo were associated with improvement in sexual function and mood , but differences between T and placebo were not distinguishable BACKGROUND Depression in older men has been associated with low circulating testosterone concentration but data from prospect i ve studies are limited . METHODS We conducted a prospect i ve longitudinal study in a community representative cohort of 3179 older men free of clinical ly significant depressive symptoms at baseline . The main objective of this study was to determine if low serum testosterone , dihydrotestosterone and estradiol concentrations are associated with the development of depressive symptoms . Incident depression was assessed with the Patient Health Question naire and via an electronic health record data base ( The West Australian Data Linkage System ) . The main exposures of interest were serum testosterone , dihydrotestosterone and estradiol measured by liquid chromatography-mass spectrometry and calculated free testosterone in baseline blood sample s ( collected between 2001 and 2004 ) . RESULTS One hundred and thirty five men ( 4.2 % ) developed depression over a median follow up time of 9.4 years ( range 8.4 - 10.9 ) . Men with incident depression were older ( median age 77.7 vs 76.1 years , z=-3.82 , p=0<0.001 ) and were more likely to have cardiovascular disease ( 43.0 % vs 32.6 % , χ(2)=6.32 , p=0.012 ) and diabetes ( 22.2 % vs 13.2 % , χ(2)=8.95 , p=0.003 ) . Low serum total testosterone ( < 6.4 nmol/L ) was associated with incident depression ( HR 2.07 , 95%CI 1.17 - 3.68 ) and this remained significant after adjustment for relevant potential confounding factors ( HR 1.86 , 95%CI 1.05 - 3.31 ) . Low serum dihydrotestosterone , estradiol and calculated free testosterone were not associated with risk of depression . CONCLUSIONS Low serum total testosterone , but not calculated free testosterone , was associated with incident depression in this sample of older men BACKGROUND Gonadal steroid levels decline with age in men . Whether low testosterone levels affect the development of common age-related disorders , including physical functioning and falling , is unclear . METHODS This longitudinal , observational follow-up study sought to determine whether low testosterone levels are associated with physical performance and fall risk in older men . A total of 2587 community-based men aged 65 to 99 years were selected using a stratified r and om sampling scheme from a study cohort of 5995 volunteers .  Bioavailable testosterone and estradiol levels and physical performance measures were determined from baseline . Incident falls were ascertained every 4 months during 4 years of follow-up . Generalized estimating equations were used to estimate risk ratios for the relation of sex steroids to falls . RESULTS Fifty-six percent of the men reported at least 1 fall ; many fell frequently . Lower bioavailable testosterone levels were associated with increased fall risk . Men with testosterone levels in the lowest quartile had a 40 % higher fall risk than those in the highest quartile . The effect of low testosterone levels was most apparent in younger men ( 65 - 69 years ) ( relative risk , 1.8 ; 95 % confidence interval , 1.2 - 2.7 ) ; testosterone level was not associated with falls in the oldest men ( > /=80 years ) . Lower testosterone concentrations were associated with reduced physical performance . However , the association between low testosterone levels and fall risk persisted despite adjustment for performance . CONCLUSIONS Falls were common among older men . Fall risk was higher in men with lower bioavailable testosterone levels . The effect of testosterone level was independent of poorer physical performance , suggesting that the effect of testosterone on fall risk may be mediated by other and rogen actions The prevalence of depression in chronic obstructive pulmonary disease ( COPD ) is greater than in the general population , but the mechanism is unknown . Depression has been linked mechanistically to testosterone deficiency , and testosterone deficiency ( hypogonadism ) affects many men with COPD . Accordingly , we hypothesized that significant depressive symptoms would be associated with hypogonadism in men with COPD . The hypothesis was tested in a prospect i ve cross-sectional investigation of 104 men ( FEV1 = 43 ± 1 % predicted ( ±SE ) ) , 36 of whom had significant depressive symptoms ( Geriatric Depression Scale score or GDS ≥ 11 ) . Hypogonadism was present in 14 patients with GDS ≥ 11 ( 39 % ) and in 21 with GDS < 11 ( 31 % ; p = 0.41 ) . The independent association between depressive symptoms and gonadal state was evaluated after adjusting for potential confounders : combined severity of lung disease and functional impairment ( BODE-index ) , co-morbidities ( Charlson co-morbidity-Index ) , age , active smoking , education , and marital status . After controlling for confounding variables , multivariable logistic-regression analysis revealed that only BODE-index ( odds ratio 1.40 ; p = 0.003 ) , lack of companion ( 2.73 ; p = 0.045 ) and younger age ( 0.93 ; p = 0.021 ) were independently associated with depressive symptoms . In a secondary analysis , patients were stratified into those with severe depressive symptoms ( GDS ≥ 19 ) and those with mild depressive symptoms ( GDS 11 - 18 ) . Prevalence of hypogonadism was greater in first group than in the second ( 62 % vs. 26 % ; p = 0.036 ) . After controlling for confounders , however , gonadal state was not associated with severe depressive symptoms . Similarly , gonadal state was not associated with mood and motivation subscale scores of the GDS . In conclusion , presence of significant depressive symptoms was not associated with hypogonadism in men with COPD
INTERPRETATION We found weak correlation between signs , symptoms and testosterone levels , uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition .
It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men
BACKGROUND Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men .
We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men .