A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Relationship Between Depressive Symptoms and Hypogonadism in Men with COPD Identification of late-onset hypogonadism in middle-aged and elderly men. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism The Pituitary-Gonadal Axis and Health in Elderly Men: A Study of Men Born in 1913 Safety and Efficacy of Testosterone Gel 1% Augmentation in Depressed Men With Partial Response to Antidepressant Therapy Testosterone gel monotherapy improves sexual function of hypogonadal men mainly through restoring erection: evaluation by IIEF score. Relationship between the Saint Louis University ADAM questionnaire and sexual hormonal levels in a male outpatient population over 50 years of age. Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men? Effect of Testosterone Solution 2% on Testosterone Concentration, Sex Drive and Energy in Hypogonadal Men: Results of a Placebo Controlled Study. Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism. Long‐term efficacy and safety of a permeation‐enhanced testosterone transdermal system in hypogonadal men Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection. The Sexual Effects of Testosterone Replacement in Depressed Men: Randomized, Placebo-Controlled Clinical Trial
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 BACKGROUND Symptoms of male hypogonadism include low libido , fatigue , and dysphoria and are alleviated with testosterone replacement . The prevalence of major depressive disorder ( MDD ) in hypogonadal men is not known , nor is the antidepressant efficacy of testosterone replacement in depressed , hypogonadal men . METHOD A 6-week double-blind , placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level , defined as total serum testosterone < or = 350 ng/dL. Patients were r and omly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate , 200 mg , or sesame seed oil ( placebo ) . The primary outcome measure was the 24-item Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Thirty patients were r and omly assigned to an intervention ; 13 received testosterone , and 17 received placebo .  Mean + /- SD age was 52+/-10 years , mean testosterone level was 266.1+/-50.6 ng/dL , and mean baseline HAM-D score was 21+/-8 . All patients who received testosterone achieved normalization of their testosterone levels . The HAM-D scores decreased in both testosterone and placebo groups , and there were no significant between-group differences : reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo .  Response rate , defined as a 50 % or greater reduction in HAM-D score , was 38.5 % ( 5/13 ) for patients who received testosterone and 41.2 % ( 7/17 ) for patients who received placebo . Patients receiving testosterone had a marginal but statistically significant improvement in sexual function ( p = .02 ) . CONCLUSION In this clinical trial with depressed , hypogonadal men , antidepressant effects of testosterone replacement could not be differentiated from those of placebo 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 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 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 ) Secondary hypogonadism is not an infrequent abnormality in older patients presenting with the primary complaint of erectile dysfunction . Because of the role of testosterone in mediating sexual desire and erectile function in men , these patients are usually treated with exogenous testosterone , which , while elevating the circulating and rogens , suppresses gonadotropins from the hypothalamic-pituitary axis . The response of this form of therapy , although extolled in the lay literature , has usually not been effective in restoring or even improving sexual function . This failure of response could be the result of suppression of gonadotropins or the lack of a cause and effect relationship between sexual function and circulating and rogens in this group of patients . Further , because exogenous testosterone can potentially increase the risk of prostate disease , it is important to be sure of the benefit sought , i.e. an increase in sexual function . In an attempt to answer this question , we measured the hormone levels and studied the sexual function in 17 patients with erectile dysfunction who were found to have secondary hypogonadism . This double blind , placebo-controlled , cross-over study consisted of treatment with clomiphene citrate and a placebo for 2 months each . Similar to our previous observations , LH , FSH , and total and free testosterone levels showed a significant elevation in response to clomiphene citrate over the response to placebo . However , sexual function , as monitored by question naires and nocturnal penile tumescence and rigidity testing , did not improve except for some limited parameters in younger and healthier men . The results confirmed that there can be a functional secondary hypogonadism in men on an out-patient basis , but correlation of the hormonal status does not universally reverse the associated erectile dysfunction to normal , thus requiring closer scrutiny of cl aims of cause and effect relationships between hypogonadism and erectile dysfunction PURPOSE Although there is no evidence that testosterone therapy increases the risk of prostate cancer , there is a paucity of long-term data . We determined whether the incidence of prostate cancer is increased in hypogonadal men receiving long-term testosterone therapy .  MATERIAL S AND METHODS In 3 parallel , prospect i ve , ongoing , cumulative registry studies 1,023 hypogonadal men received testosterone therapy .  Two study cohorts were treated by urologists ( since 2004 ) and 1 was treated at an academic and rology center ( since 1996 ) . Patients were treated when  total testosterone was 12.1 nmol/l or less ( 350 ng/dl ) and symptoms of hypogonadism were present . Maximum followup was 17 years ( 1996 to 2013 ) and median followup was 5 years . Mean baseline patient age in the urological setting s was 58 years and in the and rology setting it was 41 years . Patients received testosterone undecanoate injections in 12-week intervals . Pretreatment examination of the prostate and monitoring during treatment were performed . Prostate biopsies were performed according to EAU guidelines . RESULTS Numbers of positive and negative biopsies were assessed . The incidence of prostate cancer and post-prostatectomy outcomes was studied . A total of 11 patients were diagnosed with prostate cancer in the 2 urology setting s at proportions of 2.3 % and 1.5 % , respectively . The incidence per 10,000 patient-years was 54.4 and 30.7 , respectively . No prostate cancer was reported by the and rology center . Limitations are inherent in the registry design without a control group . CONCLUSIONS Testosterone therapy in hypogonadal men does not increase the risk of prostate cancer . If guidelines for testosterone therapy are properly applied , testosterone treatment is safe in hypogonadal men PURPOSE Benign prostatic hyperplasia and hypogonadism are common disorders in aging men . There is concern that and rogen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia . We examined whether combining dutasteride , which inhibits testosterone to dihydrotestosterone conversion , with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces and rogenic stimulation of the prostate compared to testosterone alone . MATERIAL S AND METHODS We conducted a double-blind , placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia , prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl ( less than 9.7 nmol/l ) . Subjects were r and omized to daily transdermal 1 % T gel plus oral placebo or dutasteride for 6 months . Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl . The primary outcomes were prostate volume measured by magnetic resonance imaging , serum prostate specific antigen and and rogen levels . RESULTS A total of 46 subjects completed all procedures . Serum testosterone increased similarly into the mid-normal range in both groups . Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group . In the testosterone plus dutasteride  group prostate volume and prostate specific antigen ( mean ± SEM ) decreased 12 % ± 2.5 % and 35 % ± 5 % , respectively , compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5 % ± 3.3 % and 19 % ± 7 % ( p = 0.03 and p = 0.008 ) , respectively , after 6 months of treatment . Prostate symptom scores improved in both groups . CONCLUSIONS Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only . Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from and rogenic stimulation during testosterone replacement in older , hypogonadal men with symptomatic benign prostatic hyperplasia BACKGROUND The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms ( diminished libido , depressed mood , low energy , and depleted muscle mass ) in men with symptomatic human immunodeficiency virus illness . METHODS Seventy-four patients were enrolled in a double-blind , placebo-controlled 6-week trial with bi-weekly testosterone injections , followed by 12 weeks of open-label maintenance treatment . Major outcome measures were Clinical Global Impressions Scale ratings for libido , mood , energy , and erectile function ; Hamilton Depression Rating Scale scores , and Chalder Fatigue Scale scores . Body composition changes were assessed with bioelectric impedance analysis . RESULTS Seventy men completed the 6-week trial . Response rates , defined as much or very much improved libido , were 74 % ( 28/38 ) for patients r and omized to testosterone , and 19 % ( 6/32 ) for placebo-treated patients ( P<.001 ) . Of the 62 completers with fatigue at baseline , 59 % ( 20/34 ) receiving testosterone and 25 % ( 7/28 ) receiving placebo reported improved energy ( P<.01 ) . Among the 26 completers with an Axis I depressive disorder at baseline , 58 % of the testosterone-treated patients reported improved mood compared with 14 % of placebo-treated patients ( Fisher exact test = .08 ) . With testosterone treatment , average increase in muscle mass over 12 weeks was 1.6 kg for the whole group , and 2.2 kg for the 14 men with wasting at baseline . Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks . CONCLUSION Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness , restoring libido and energy , alleviating depressed mood , and increasing muscle mass Background : No r and omized study exists comparing the effects of different modes of and rogen substitution on bone mineral density ( BMD ) . Methods : We performed a prospect i ve , r and omized , trial assigning 53 hypogonadal men to the following treatment groups : mesterolone 100 mg p.o . daily , testosterone undecanoate 160 mg p.o . daily , testosterone enanthate 250 mg i.m . every 21 days , or a single subcutaneous implantation of 1,200 mg crystalline testosterone .  The BMD was determined by peripheral quantitative computed tomography . Results : At baseline , men with secondary hypogonadism ( n = 33 ) had a lower BMD ( –1.52 ± 0.23 SDS ; Z-scores ) than men with primary hypogonadism ( n = 20 , –0.87 ± 0.23 SDS , p < 0.01 ) . In men with primary hypogonadism , the BMD increased dose dependently ( crystalline testosterone + 7.0 ± 1.3 % , testosterone enanthate + 4.8 ± 0.2 % , testosterone undecanoate + 3.4 ± 2.5 % , mesterolone + 0.8 ± 1.6 % ) after 6 months of therapy . Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD . Conclusions : In primary hypogonadal men the BMD responds dose dependently to testosterone substitution , whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD 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 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 OBJECTIVES To use the International Index of Erectile Function ( IIEF ) to evaluate the improvement of erectile function and other sexual functions after testosterone monotherapy . Testosterone replacement therapy alone was reported to be effective for the improvement in sexual function in hypogonadal males . However , it is still unclear that which kind of the sexual function is most beneficial and to what extent the sexual function could be improved . METHODS A double-blind , r and omized , placebo-controlled study was conducted with a treatment group ( n = 20 ) and control group ( n = 20 ) . Using a critical review of the different sexual functional domain scores of the IIEF-15 and the scores of the IIEF-5 , we evaluated the sexual function of men in hypogonadal status before and after 3 months of testosterone gel treatment . Effect size was used to compare the drug effects for each sexual functional domain , and the results were confirmed by multivariate analysis . RESULTS A total of 30 men remained at the end of the study . After 3 months of testosterone gel therapy for the hypogonadal men , the most beneficial effect on sexual function was erectile function , with sexual desire and orgasmic satisfaction insignificantly affected . CONCLUSIONS The results of our study have shown that transdermal testosterone gel treatment for hypogonadal patients can improve their sexual dysfunction mainly through restoring erectile function 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 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 PURPOSE We determined the effect of testosterone solution 2 % on total testosterone level and the 2 symptoms of hypogonadism , sex drive and energy level . MATERIAL S AND METHODS This was a r and omized , multicenter , double-blind , placebo controlled , 16-week study to compare the effect of testosterone and placebo on the proportion of men with a testosterone level within the normal range ( 300 to 1,050 ng/dl ) upon treatment completion . We also assessed the impact of testosterone on sex drive and energy level measured using SAID ( Sexual Arousal , Interest and Drive scale ) and HED ( Hypogonadism Energy Diary ) , respectively . A total of 715 males 18 years old or older with total testosterone less than 300 ng/dl and at least 1 symptom of testosterone deficiency ( decreased energy and /or decreased sexual drive ) were r and omized to 60 mg topical testosterone solution 2 % or placebo once daily . RESULTS Of study completers 73 % in the testosterone vs 15 % in the placebo group had a testosterone level within the normal range at study end point ( p < 0.001 ) . Participants assigned to testosterone showed greater baseline to end point improvement in SAID scores ( low sex drive subset p < 0.001 vs placebo ) and HED scores ( low energy subset p = 0.02 vs placebo , not significant at prespecified p < 0.01 ) . No major adverse cardiovascular or venous thrombotic events were reported in the testosterone group . The incidence of increased hematocrit was higher with testosterone vs placebo ( p = 0.04 ) . CONCLUSIONS Once daily testosterone solution 2 % for 12 weeks was efficacious in restoring normal testosterone levels and improving sexual drive  in hypogonadal men . Improvement was also seen in energy levels on HED though not at the prespecified p < 0.01 . No new safety signals were identified This study was design ed to evaluate the safety and effectiveness of testosterone therapy for clinical symptoms of hypogonadism ( low libido , low mood , low energy , loss of appetite/weight ) in human immunodeficiency virus-positive men with CD4 cell counts less than 400 cells/mm3 and deficient or low normal serum testosterone levels . The trial consisted of 8 weeks of open treatment with 400 mg of intramuscular testosterone cypionate biweekly . Responders were maintained at this dosage for another 4 weeks and then were r and omized in a double-blind , placebo-controlled , 6-week discontinuation trial . Of the 112 men who completed at least 8 weeks of treatment , 102 ( 91 % ) were rated as responders on a global assessment of sexual desire/function .  Of the 34 study completers with major depressive disorder and /or dysthymia , 79 % reported significant improvement in mood at week 8 . Average weight change was a gain of 3.7 pounds , with 45 % gaining more than 5 pounds . Eighty-four men entered and 77 completed the double-blind phase ; of these , 78 % of completers r and omized to testosterone and 13 % r and omized to placebo maintained their response . No significant medical or immunologic adverse effects were identified . Testosterone therapy was well tolerated and effective in ameliorating symptoms of clinical hypogonadism , and equally so for men with and without testosterone deficiency . For patients with major depression and /or dysthymia , improvement was equal to that achieved with st and ard antidepressants An important aim in treating male hypogonadism is restoration of physiological concentrations of testosterone and its metabolites . We have assessed hormone levels , pharmacokinetics and clinical response , including safety , of a permeation‐enhanced testosterone transdermal system ( TTD ) in the treatment of hypogonadal men for a 12‐month period OBJECTIVE To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas ( NFPA ) . PATIENTS AND METHODS Open label , single-arm , prospect i ve trial . Nine hypogonadal men ( testosterone < 300 ng/dL and low/normal LH ) with previously treated NFPA .  Clomiphene ( 50 mg/day orally ) for 12 weeks . Testosterone , estradiol , LH , FSH , prolactin and erectile function were evaluated before and after 10 days , 4 , 8 and 12 weeks of clomiphene treatment . RESULTS After clomiphene treatment , testosterone and erectile function improved in only one patient . In the remaining eight patients , testosterone levels decreased whereas LH , FSH , and estradiol remained unchanged . Insulin sensitivity increased in unresponsive patients . CONCLUSIONS Compared with hypogonadal men with prolactinomas under dopaminergic therapy , clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA AIM Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone , but also with a rise in serum estradiol . These endocrine changes negatively affect libido , sexual function , mood , behavior , lean body mass , and bone density . Currently , the most common treatment is exogenous testosterone therapy . This treatment can be associated with skin irritation , gynecomastia , nipple tenderness , testicular atrophy , and decline in sperm counts . In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone ( T ) and improving the testosterone/estrogen ( T/E ) ratio . METHODS Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospect ively . Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed . RESULTS The mean age was 39 years , and the mean pretreatment testosterone and estrogen levels were 247.6 + /- 39.8 ng/dL and 32.3 + /- 10.9 , respectively . By the first follow-up visit ( 4 - 6 weeks ) , the mean testosterone level rose to 610.0 + /- 178.6 ng/dL ( P < 0.00001 ) . Moreover , the T/E ratio improved from 8.7 to 14.2 ( P < 0.001 ) . There were no side effects reported by the patients . CONCLUSIONS Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estradiol ratio in men with hypogonadism . This therapy represents an alternative to testosterone therapy by stimulating the endogenous and rogen production pathway 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 PURPOSE Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients . Men with acquired immunodeficiency syndrome ( AIDS ) lose body cell mass . Hypogonadism is also common . This study tested the efficacy of a testosterone transscrotal patch ( 6 mg/day ) in improving body cell mass and treating hypogonadism in these patients . SUBJECTS AND METHODS This multicenter , r and omized , double-blinded , placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men , 18 years of age and older , who had AIDS , 5 % to 20 % weight loss , and either a low morning serum total testosterone level ( < 400 ng/dL ) or a low free testosterone level ( < 16 pg/mL ) . Outcomes included weight , body cell mass as measured using bioelectrical impedance analysis , quality of life , and morning measurements of serum testosterone and dihydrotestosterone levels , lymphocyte subsets , and HIV quantification . RESULTS There were no significant differences in baseline weight , CD4 cell counts , or HIV serum viral quantification between treatment arms . Morning total and free testosterone levels increased in those treated with testosterone , but not with placebo . Following 12 weeks of treatment there were no differences ( testosterone-placebo ) in mean weight change ( -0.3 kg [ 95 % confidence interval ( CI ) : -1.4 to 0.8 ] ) or body cell mass ( -0.2 kg [ 95 % CI : -1.0 to 0.6 ] ) in the two groups . There were also no changes in quality of life in either group . CONCLUSION Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch . However , this system of replacement does not improve weight , body cell mass , or quality of life 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
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 .