Prevalence of symptomatic androgen deficiency in men. Factors associated with vertebral fractures in men treated with androgen deprivation therapy for prostate cancer. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial Correlates of low testosterone in men with chronic spinal cord injury Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer. Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism Testosterone supplementation improves spatial and verbal memory in healthy older men Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Decreased testosterone levels in men with rheumatoid arthritis: effect of low dose prednisone therapy. An osteoporosis screening tool for Chinese men Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency A double-blind, placebo-controlled, randomized clinical trial of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency Randomized placebo‐controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy. Osteoporosis medication and reduced mortality risk in elderly women and men. Alendronate for the treatment of osteoporosis in men.
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 PURPOSE And rogen deprivation therapy for prostate cancer causes accelerated loss of bone mineral density and is associated with increased fracture risk . We evaluated risk factors associated with vertebral fractures among men enrolled in a fracture prevention trial . MATERIAL S AND METHODS Analysis included men receiving and rogen deprivation therapy for prostate cancer and enrolled in a phase III fracture prevention trial . All men were 70 years old or older or had a low bone mineral density ( T-score less than -1.5 for the lumbar spine or total hip ) . We analyzed demographic and laboratory characteristics of men with and those without vertebral fractures at study entry . RESULTS Of the 1,244 subjects 162 ( 13.0 % ) had a vertebral fracture at baseline . The 2 factors significantly associated with vertebral fractures were white race ( p=0.028 compared with nonwhite race ) and osteoporosis ( p=0.002 for osteoporosis at any site , p=0.053 for osteoporosis at the spine , p=0.002 for osteoporosis at the hip ) . Lower bone mineral density was also significantly associated with vertebral fractures when analyzed as a continuous variable . Factors not associated with vertebral fractures included age , country of residence , and rogen deprivation therapy duration at baseline , and rogen deprivation therapy mode , body mass index , testosterone , estradiol , C-telopeptide , bone specific alkaline phosphatase and osteocalcin . Results were similar in analyses limited to men 70 years old or older . CONCLUSIONS White race and low bone mineral density were significantly associated with vertebral fractures in this study of men treated with and rogen deprivation for prostate cancer . These observations should inform the assessment and management of fracture risk among such men This open , prospect i ve therapeutic trial studied the effects of regular moderate and rogen supplementation on bone mineral density in eugonadal men with established osteoporosis , and collected data on the safety of and rogen therapy used in this setting . 23 men , aged 34 - 73 years , with vertebral crush fractures and back pain , in whom secondary causes of osteoporosis had been excluded , were treated with fortnightly intramuscular injections of 250 mg testosterone esters ( Sustanon 250(R ) ) for 6 months . Blood pressure was recorded monthly ; fasting lipids , glucose , haematocrit , plasma viscosity , and testosterone levels were measured every 3 months . Psychological effects were assessed using the Hospital Anxiety and Depression Scale ( HADS ) and General Health Question naire ( GHQ ) , together with question ing on libido changes . Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry ( DEXA ) over the treatment period . 21 men completed the study period .  Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2 ) to 0.839 g/cm(2 ) during treatment ( p < 0 . 001 ) , a rise of 5 % in 6 months . Bone mineral density at the hip did not change . There were significant , favorable changes in diastolic blood pressure ( -4.7 mmHg , p < 0.01 ) , serum triglyceride levels ( -0.405 mmol/L , p < 0.01 ) , and total cholesterol ( -0.27 mmol/L , p < 0.05 ) . Adverse changes included a fall in HDL cholesterol ( -0.087 mmol/L , p < 0.05 ) and a rise in plasma viscosity which was significant at 3 months but not at 6 months . The expected rises in hematocrit ( 0.434 to 0.456 ) and FAI ( 0.504 to 0.887 ) occurred . We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis , without an overall adverse effect on cardiovascular risk factors . This treatment warrants further evaluation in a r and omized , controlled trial CONTEXT Risk factors for low testosterone and symptomatic and rogen deficiency ( AD ) may be modifiable . OBJECTIVE Our objective was to examine demographic , anthropometric , and medical correlates of low testosterone and symptomatic AD . DESIGN Data were used from the Boston Area Community Health Survey , an epidemiological study conducted from 2002 - 2005 . SETTING Data were obtained from a community-based r and om sample of racially and ethnically diverse men . PATIENTS OR OTHER PARTICIPANTS Data were available for 1822 men . MAIN OUTCOME MEASURES Multivariate logistic regression  was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) for associations of covariates with 1 ) low testosterone and 2 ) symptomatic AD . The operational definition of low testosterone was serum total testosterone less than 300 ng/dl and free testosterone less than 5 ng/dl ; symptomatic AD was defined as the additional presence of symptoms : any of low libido , erectile dysfunction , or osteoporosis or two or more of sleep disturbance , depressed mood , lethargy , or diminished physical performance . RESULTS Factors associated with low testosterone included age ( OR = 1.36 ; 95 % CI= 1.11 - 1.66 , per decade ) , low per-capita income ( $ 6000 or less per household member vs. more than $ 30,000 ; OR = 2.86 ; 95 % CI = 1.39 - 5.87 ) , and waist circumference ( per 10-cm increase ; OR = 1.75 ; 95 % CI = 1.45 - 2.12 ) . Only age ( OR = 1.36 ; 95 % CI = 1.04 - 1.77 ) , waist circumference ( OR = 1.88 ; 95 % CI = 1.44 - 2.47 ) , and health status ( OR = 0.21 ; 95 % CI = 0.05 - 0.92 , excellent vs. fair/poor ) were associated with our construct of symptomatic AD . Of all variables , waist circumference was the most important contributor in both models . CONCLUSIONS Waist circumference is a potentially modifiable risk factor for low testosterone and symptomatic AD . Manifestation of symptoms may be a consequence of generally poor health status 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 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 PURPOSE It is well described in the urological literature that and rogen deprivation can result in accelerated bone breakdown and osteoporosis . Therefore , we evaluate the degree of bone breakdown in patients on conventional and rogen deprivation with those on diethylstilbesterol alone or in conjunction with luteinizing hormone releasing hormone agonists  or orchiectomy . MATERIAL S AND METHODS During an 18-month period a total of 54 patients with clinical ly localized prostate cancer and 24 with benign prostatic hyperplasia were evaluated . All patients with prostate cancer were either treated with external beam radiotherapy without and rogen deprivation or were started on and rogen deprivation therapy . All patients were prospect ively followed and evaluated for serum testosterone and estradiol along with urinary collagen type I cross-linked N-telopeptides . Three separate morning urine sample s on 3 separate months were collected on each patient and analyzed for N-telopeptides . To correct for different levels of renal function , all N-telopeptides were measured as a ratio of urinary N-telopeptides/urine creatinine . All patients with any bone or skeletal abnormalities were excluded from study as were those with osseous metastatic disease . RESULTS There was a statistically significant ( p < 0.05 ) higher level of urinary N-telopeptides/creatinine in patients on and rogen deprivation therapy  who were not treated with diethylstilbesterol . The estrogenic effect of diethylstilbesterol protects one from bone resorption .  Patients on diethylstilbesterol  did not have any higher levels of bone breakdown than patients with benign prostatic hyperplasia or those who never received any and rogen deprivation . CONCLUSIONS Rapid bone turnover and resorption can be prevented with 1 mg . diethylstilbesterol alone or in conjunction with other modes of and rogen deprivation . Therefore , diethylstilbesterol should be considered as monotherpy in men who require long-term anti and rogen therapy 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 Objective : To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men . Background : Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass , osteoporosis , decreased sexual activity , and changes in cognition . Methods : Twenty-five healthy , community-dwelling volunteers , aged 50 to 80 years , completed a r and omized , double-blind , placebo-controlled study . Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo ( saline ) for 6 weeks . Cognitive evaluations were conducted at baseline , week 3 , and week 6 of treatment by use of a battery of neuropsychologic tests . Results : Circulating total testosterone was raised an average of 130 % from baseline at week 3 and 116 % at week 6 in the treatment group . Because of aromatization of testosterone , estradiol increased an average of 77 % at week 3 and 73 % at week 6 in the treatment group . Significant improvements in cognition were observed for spatial memory ( recall of a walking route ) , spatial ability ( block construction ) , and verbal memory ( recall of a short story ) in older men treated with testosterone compared with baseline and the placebo group , although improvements were not evident for all measures . Conclusions : The results suggest that short-term testosterone administration enhances cognitive function in healthy older men . However , it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels , or both . The potential role of testosterone vs its metabolites on cognition requires further research 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 OBJECTIVE To determine whether men with rheumatoid arthritis ( RA ) have abnormal hypothalamic-pituitary-gonadal axis function and to measure the effects of low dose prednisone therapy in these patients . METHODS We measured testosterone , follicle stimulating hormone ( FSH ) , and luteinizing hormone ( LH ) in 36 men aged 38 - 75 ( mean age + /- 1 sd = 62 + /- 10 years ) who had longst and ing active RA ( mean disease duration = 17 + /- 12 years ) and in 70 healthy elderly male controls , aged 53 - 83 ( mean age 68 = + /- 6 years ) . We divided the group with RA into those taking no prednisone ( n = 12 ) and those taking 5 to 10 mg/day of prednisone ( n = 24 ) and analyzed these groups separately to determine whether low doses of prednisone affected testosterone levels . RESULTS Compared to the healthy controls , patients with RA not taking prednisone had normal testosterone levels but significantly elevated levels of FSH and LH ( p < 0.01 for both comparisons ) . In contrast , patients with RA taking prednisone had significantly lower testosterone levels ( p < 0.05 ) , but levels of FSH and LH were only slightly elevated compared to controls . Compared to patients not taking prednisone , patients taking prednisone had lower levels of testosterone , FSH , and LH . CONCLUSION Male patients with RA who are not taking prednisone have significantly elevated levels of FSH and LH with normal testosterone levels , suggesting a state of compensated partial gonadal failure . Male patients with RA taking low doses of prednisone have lower testosterone and gonadotropin levels , suggesting that prednisone may suppress the hypothalmic-pituitary-testicular axis . Since testosterone affects immune function as well as bone and muscle metabolism , and rogen deficiency in some men with RA may predispose these patients to more severe disease and to increased complications of steroid therapy such as myopathy and osteoporosis Several osteoporosis risk instruments have been proposed to select women for bone densitometry , but no vali date d instruments are currently available for men . This study aims to address this deficiency by developing and validating a Male Osteoporosis Screening Tool ( MOST ) for Chinese men . Two thous and ambulatory men , aged 65 and above , were recruited from the general community in Hong Kong , and a cohort of 1,970 men with valid total hip and lumbar spine dual-energy X-ray absorptiometry ( DXA ) measurements was included in the current analysis . A 60 % r and om sample was selected as the training sample for developing the screening tool , and the remaining 40 % constituted the validation sample . Logistic regression and receiver operating characteristic ( ROC ) analysis were used to identify the simplest combination of risk factors to be included in the screening tool for predicting osteoporosis at the femoral neck , total hip , or lumbar spine . Body weight and quantitative ultrasound index ( QUI ) were found to contribute significantly to the area under the ROC curve ( AUC ) , yielding an AUC of 0.823 in the training sample . The result ing MOST had a sensitivity of 94 % and a specificity of 46 % when using a cutoff score of 3 . MOST had an AUC of 0.839 in the validation sample . The risk of osteoporosis was 1 % among those with MOST scores ≤2 , but 72 % among those with MOST scores > 7 . Using a cutoff of 3 , the negative predictive value was 97.5 % which suggests that the 42 % with MOST scores ≤3 may be accurately screened out as being without osteoporosis , thus saving two fifths of our DXA re sources . The positive predictive value was 72 % when using a cutoff of 7 , implying that MOST can not replace DXA for case-finding purpose s. Nevertheless , for re source allocation and patient satisfaction , it is prudent and economical to offer DXA screening first to the 6 % with MOST scores > 7 Little is known about the descriptive epidemiology of and rogen deficiency . In this study , we sought to address this issue by providing estimates of the crude and age-specific prevalence and incidence rates of and rogen deficiency in a r and omly sample d population -based cohort of middle-aged and older men . Data on and rogen deficiency ( defined using both signs/symptoms plus total and calculated free testosterone ) were available for n = 1691 ( baseline ) and n = 1087 ( follow-up ) men from the Massachusetts Male Aging Study .  Crude and age-specific prevalence and incidence rates were calculated . Based on these estimates , projections for the number of cases of and rogen deficiency in the 40- to 69-yr-old U.S. male population were computed . Estimates of the crude prevalence of and rogen deficiency at baseline and follow-up were 6.0 and 12.3 % , respectively . Prevalence increased significantly with age . From baseline age-specific prevalence data , it is estimated that there are approximately 2.4 million 40- to 69-yr-old U.S. males with and rogen deficiency . The crude incidence rate of and rogen deficiency was 12.3 per 1,000 person-years , and the rate increased significantly ( P < 0.0001 ) with age . Based on these incidence data , we can expect approximately 481,000 new cases of and rogen deficiency per year in U.S. men 40 - 69 yr old 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 Despite partial and rogen deficiency , the safety and efficacy of  and rogen therapy in older men remains controversial because controlled studies of testosterone have given equivocal results . Human chorionic gonadotropin ( hCG ) can be conveniently and infrequently self-administered , and it increases not only circulating testosterone but also estradiol and other testicular steroids . We evaluated the efficacy and safety of 3 months of treatment with sc recombinant hCG ( r-hCG , Ovidrel ) on muscle mass , strength , mobility , and physical activity in ambulant , community-dwelling men more than 60 yr old having partial and rogen deficiency ( testosterone < or = 15 nmol/liter , twice ) . Forty eligible men ( mean age , 67 yr ; range , 60 - 85 yr ) were r and omized to receive r-hCG ( 5000 IU , 250 microg ) or placebo by twice weekly sc self-injection and were studied before treatment , monthly during treatment , and 1 month after treatment . All completed the study , and treatment groups were well matched . r-hCG significantly increased body weight ( approximately 1 kg ; P < 0.05 ) and lean body mass ( approximately 2 kg ; P < 0.001 ) and reduced fat mass ( approximately 1 kg , P < 0.05 ) . However , anthropometric measures of skinfold thickness ( biceps , triceps , subscapular , suprailiac ) and circumferences ( midarm , waist , hip , and midthigh ) , including the waist-hip ratio , did not change significantly . Shoulder and knee strength ( peak torque ) , as measured by isokinetic and isometric dynamometry , was not significantly increased , nor was physical activity ( accelerometry and Physical Activity Scale for Elderly self-report ) or gait and balance ( modified Guralnik and Frailty and Injuries : Cooperative Studies of Intervention Techniques performance batteries ) altered . Total and free testosterone and estradiol were markedly ( 150 % ; P < 0.001 ) and stably increased , whereas LH , FSH , and urea were significantly decreased . Testis volume was significantly decreased ( approximately 5 ml ; P < 0.05 ) . There were no significant changes in hemoglobin , osteocalcin , or prostate-specific antigen , and the International Prostate Symptom Score did not change . Three men developed nipple tenderness that did not progress to gynecomastia . We conclude that 3 months of treatment with twice weekly r-hCG demonstrates sustained and rogenic effects on hormones and muscle mass but has no effect on muscle strength or physical functioning The efficacy and safety of and rogen supplementation in older men remains controversial . Despite biochemical evidence of partial and rogen deficiency in older men , controlled studies using T demonstrate equivocal benefits . Furthermore , the importance of aromatization and 5alpha reduction in and rogen actions among older men remains unclear . Dihydrotestosterone is the highest potency natural and rogen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction . Therefore , the effects of dihydrotestosterone may differ from those of T in older men . This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength , mobility , and quality of life in ambulant , community-dwelling men aged 60 yr or older . Eligible men ( plasma T < or = 15 nmol/liter ) were r and omized to undergo daily dermal application of 70 mg dihydrotestosterone gel ( n = 18 ) or vehicle ( n = 19 ) and were studied before , monthly during , and 1 month after treatment . Among 33 ( 17 dihydrotestosterone , 16 placebo ) men completing the study with a high degree of compliance , dihydrotestosterone had significant effects on circulating hormones ( increased dihydrotestosterone ; decreased total and free testosterone , LH , and FSH ; unchanged SHBG and estradiol ) , lipid profiles ( decreased total and low-density lipoprotein cholesterols ; unchanged high-density lipoprotein cholesterol and triglycerides ) , hematopoiesis ( increased hemoglobin , hematocrit , and red cell counts ) , and body composition ( decreased skinfold thickness and fat mass ; unchanged lean mass and waist to hip ratio ) . Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction , nor was there any significant change in gait , balance , or mobility tests , in cognitive function , or in quality of life scales .  Dihydrotestosterone treatment had no adverse effects on prostate ( unchanged prostate volumes and prostate-specific antigen ) and cardiovascular ( no adverse change in vascular reactivity or lipids ) safety markers . We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected and rogenic effects , short-term safety , and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function 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 OBJECTIVE Testosterone deficiency is associated with significant morbidity , and and rogen replacement in overt hypogonadism is clearly beneficial . However , there are few data concerning the response to therapy in young men with mild testosterone deficiency Purpose . Supplemental administration of and rogens has been advocated for men with sexual dysfunction ( SD ) and hypo and rogenism . The preponderance of evidence indicates that most delivery forms of testosterone ( T ) are effective but the role of dehydroepi and rosterone ( DHEA ) is controversial . A placebo-controlled , r and omized trial of oral and rogen ( T versus DHEA ) supplementation was carried out to determine their efficacy . Material s and methods . Eighty-six men with SD and decreased levels of serum T and /or DHEA , participated in a study receiving oral T undecanoate ( OTU ) ( n = 29 ) 80 mg twice daily , DHEA ( n = 28 ) 50 mg twice daily , or placebo ( n = 29 ) . Outcomes included evaluation of sexual performance by the International Index of Erectile Function ( IIEF ) , the And rogen Deficiency in the Aging Male ( ADAM ) , Aging Male Symtom Scale ( AMS ) , and Global Assessment Question naire ( GAQ ) question naires . Biochemical evaluations included measurement of T and DHEA , prolactin , gonadotropins , and PSA . Results . Seventy-nine men completed the study . There were no significant differences in outcomes as assessed by four different instruments : the ADAM , IIEF , AMS , and GAQ in regard to sexual interest or erectile function . Biochemically , a significant increase in serum DHEA between baseline and final visit was documented in the group receiving DHEA . The levels of T , on the other h and , increased insignificantly between entry and final visit in the T cohort . No biochemical changes were observed in the placebo group . Levels of PSA remained stable in all three groups . Conclusions . This study did not suggest a clinical benefit of OTU or DHEA supplementation in men with hypo and rogenism and SD . The recommended dose of OTU may have been inadequate or poorly absorbed . Increased doses or an alternative T delivery form may result in a different response The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density .  Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture .  Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density :  bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D  on fractures .  Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) PURPOSE And rogen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk . Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating and rogen deprivation therapy .  There are limited data on patients on prolonged and rogen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis . METHODS We r and omized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system . Preplanned strata included 50 patients on and rogen deprivation therapy for less than 1 year ( stratum 1 ) and 43 on and rogen deprivation therapy for greater than 1 year ( stratum 2 ) . In each stratum patients were r and omized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo . The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months . RESULTS Age , race , body mass index and osteoporosis risk factors were similar for the 2 treatments . Most patients were former smokers , had moderate alcohol intake , were not on calcium/vitamin D supplements and were relatively sedentary at baseline . In stratum 1 spine bone mineral density increased 5.95 % in the zoledronic acid arm and decreased 3.23 % in the placebo arm ( p = 0.0044 ) . In stratum 2 spine bone mineral density increased 6.08 % in the zoledronic acid arm and only increased 1.57 % in the placebo arm ( p = 0.0005 ) . Treatment was well tolerated with minimal impact on renal function . CONCLUSIONS Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on and rogen deprivation therapy for 1 year or less , or greater than 1 year . This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of and rogen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis CONTEXT Osteoporotic fractures are associated with premature mortality .  Antiresorptive treatment reduces refracture but mortality reduction is unclear . OBJECTIVE The objective of the study was to examine the effect of osteoporosis treatment [ bisphosphonates ( BP ) , hormone therapy ( HT ) , and calcium ± vitamin D only ( CaD ) ] on mortality risk . DESIGN This was a prospect i ve cohort study ( April 1989 to May 2007 ) . SETTING The study was conducted with community-dwelling elderly ( aged 60 + yr ) subjects in Dubbo , a semiurban city , Australia . SUBJECTS Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study . MAIN OUTCOME MEASURE Mortality according to treatment group was recorded . RESULTS There were 325 ( BP , n = 106 ; HT , n = 77 ; CaD , n = 142 ) women and 37 men ( BP , n = 15 ; CaD , n = 22 ) on treatment . In women , mortality rates were lower with BP 0.8/100 person-years ( 0.4 , 1.4 ) and HT 1.2/100 person-years ( 0.7 , 2.1 ) but not CaD 3.2/100 person-years ( 2.5 , 4.1 ) vs. no treatment 3.5/100 person-years ( 3.1 , 3.8 ) . Accounting for age , fracture occurrence , comorbidities , quadriceps strength , and bone mineral density , mortality risk remained lower for women on BP [ hazard ratio ( HR ) 0.3 ( 0.2 , 0.6 ) ] but not HT [ HR 0.8 ( 0.4 , 1.8 ) ] . For 429 women with fractures , mortality risk was still reduced in the BP group [ adjusted HR 0.3 ( 0.2 , 0.7 ) ] , not accounted for by a reduction in subsequent fractures . In men , lower mortality rates were observed with BP but not CaD [ BP 1.0/100 person-years ( 0.3 , 3.9 ) and CaD 3.1/100 person-years ( 1.5 , 6.6 ) vs. no treatment 4.3/100 person-years ( 3.9 , 4.8 ) ] . After adjustment , mortality was similar , although not significant [ HR 0.5 ( 0.1 , 2.0 ) ] . CONCLUSIONS Osteoporosis therapy appears to reduce mortality risk in women and possibly men BACKGROUND Despite its association with disability , death , and increased medical costs , osteoporosis in men has been relatively neglected as a subject of study . There have been no large , controlled trials of treatment in men . METHODS In a two-year double-blind trial , we studied the effect of 10 mg of alendronate or placebo , given daily , on bone mineral density in 241 men ( age , 31 to 87 years ; mean , 63 ) with osteoporosis . Approximately one third had low serum free testosterone concentrations at base line ; the rest had normal concentrations . Men with other secondary causes of osteoporosis were excluded . All the men received calcium and vitamin D supplements . The main outcome measures were the percent changes in lumbar-spine , hip , and total-body bone mineral density . RESULTS The men who received alendronate had a mean ( + /-SE ) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine , 2.5+/-0.4 percent at the femoral neck , and 2.0+/-0.2 percent for the total body ( P<0.001 for all comparisons with base line ) . In contrast , men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent ( P<0.001 for the comparison with base line ) and no significant changes in femoral-neck or total-body bone mineral density . The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites ( P<0.001 ) . The incidence of vertebral fractures was lower in the alendronate group than in the placebo group ( 0.8 percent vs. 7.1 percent , P=0.02 ) . Men in the placebo group had a 2.4-mm decrease in height , as compared with a decrease of 0.6 mm in the alendronate group ( P=0.02 ) . Alendronate was generally well tolerated . CONCLUSIONS In men with osteoporosis , alendronate significantly increases spine , hip , and total-body bone mineral density and helps prevent vertebral fractures and decreases in height
Intramuscular testosterone moderately increased lumbar bone density in men ; the results on femoral neck bone density are inconclusive .
Without bone fracture data , the available trials offer weak and indirect inferences about the clinical efficacy of testosterone on osteoporosis prevention and treatment in men
CONTEXT And rogen-deficient men are at increased risk of osteoporosis .
The extent to which testosterone can prevent and treat osteoporosis in men remains unclear .