Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. Effects of testosterone supplementation in the aging male. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized‐controlled trial Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism. Effects of electromyostimulation on muscle and bone in men with acute traumatic spinal cord injury: A randomized clinical trial Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. An investigation of the predictors of bone mineral density and response to therapy with alendronate in osteoporotic men. A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Effects of testosterone replacement in hypogonadal men. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. Factors associated with vertebral fractures in men treated with androgen deprivation therapy for prostate cancer. Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women. Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. Predictors of serum testosterone and DHEAS in African-American men. 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. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Correlates of increased lean muscle mass in women with polycystic ovary syndrome. ACE inhibitors for sarcopenia--as good as exercise training? Diet and sex hormone-binding globulin. Effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer. Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women Testosterone dose-response relationships in healthy young men. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. Baseline characteristics and the effects of five years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset: a comparative, prospective study. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency.
CONTEXT Serum testosterone levels decline significantly with aging . Testosterone supplementation to older men might beneficially affect the aging processes . OBJECTIVE To investigate the effect of testosterone supplementation on functional mobility , cognitive function , bone mineral density , body composition , plasma lipids , quality of life , and safety parameters in older men with low normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherl and s. INTERVENTION Participants were r and omly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months . MAIN OUTCOME MEASURES Functional mobility ( Stanford Health Assessment Question naire , timed get up and go test , isometric h and grip strength , isometric leg extensor strength ) , cognitive function ( 8 different cognitive instruments ) , bone mineral density of the hip and lumbar spine ( dual-energy x-ray absorptiometry scanning ) , body composition ( total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass ) , metabolic risk factors ( fasting plasma lipids , glucose , and insulin ) , quality of life ( Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules ) , and safety parameters ( serum prostate-specific antigen level , ultrasonographic prostate volume , International Prostate Symptom score , serum levels of creatinine , aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase , hemoglobin , and hematocrit ) . RESULTS A total of 207 men completed the study . During the study , lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength . Cognitive function and bone mineral density did not change . Insulin sensitivity improved but high-density lipoprotein cholesterol decreased ; by the end of the study , 47.8 % in the testosterone group vs 35.5 % in the placebo group had the metabolic syndrome ( P = .07 ) . Quality -of-life measures were no different except for one hormone-related quality -of-life measure that improved . No negative effects on prostate safety were detected . CONCLUSION Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N23688581 BACKGROUND Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass ( FFM ) and skeletal muscle and decreases in fat mass ( FM ) but have not reported the impact of baseline body composition . OBJECTIVE The objective of the study was to determine the effect , in nonobese aging men with symptoms of and rogen deficiency and low-normal serum testosterone levels , of testosterone therapy on total and regional body composition and hormonal and metabolic indices . METHODS Sixty healthy but symptomatic , nonobese men aged 55 yr or older with total testosterone ( TT ) levels less than 15 nm were r and omized to transdermal testosterone patches or placebo for 52 wk . Body composition , by dual-energy x-ray absorptiometry ( FM , FFM , skeletal muscle ) and magnetic resonance imaging ( abdominal sc and visceral adipose tissue , thigh skeletal muscle , and intermuscular fat ) and hormonal and metabolic parameters were measured at wk 0 and 52 . RESULTS Serum TT increased by 30 % ( P = 0.01 ) , and LH decreased by 50 % ( P < 0.001 ) . Relative to placebo , total body FFM ( P = 0.03 ) and skeletal muscle ( P = 0.008 ) were increased and thigh skeletal muscle loss was prevented ( P = 0.045 ) with testosterone therapy and visceral fat accumulation decreased ( P = 0.001 ) without change in total body or abdominal sc FM ; change in visceral fat was correlated with change in TT levels ( r2 = 0.36 ; P = 0.014 ) . There was a trend to increasing total and low-density lipoprotein cholesterol with placebo . CONCLUSION Testosterone therapy , relative to placebo , selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass . Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk In the present cross-sectional study of 403 independently living elderly men , we tested the hypothesis that the decreases in bone mass , body composition , and muscle strength with age are related to the fall in circulating endogenous testosterone ( T ) and estrogen concentrations . We compared various measures of the level of bioactive and rogen and estrogen to which tissues are exposed . After exclusion of subjects with severe mobility problems and signs of dementia , 403 healthy men ( age , 73 - 94 yr ) were r and omly selected from a population -based sample .  Total T ( TT ) , free T ( FT ) , estrone ( E1 ) , estradiol ( E2 ) , and sex hormone-binding globulin ( SHBG ) were determined by RIA . Levels of non-SHBG-bound T ( non-SHBG-T ) , FT ( calc-FT ) , the TT/SHBG ratio , non-SHBG-bound E2 , and free E2 were calculated . Physical characteristics of aging included muscle strength measured using dynamometry , total body bone mineral density ( BMD ) , hip BMD , and body composition , including lean mass and fat mass , measured by dual-energy x-ray absorptiometry . In this population of healthy elderly men , calc-FT , non-SHBG-T , E1 , and E2 ( total , free , and non-SHBG bound ) decreased significantly with age . T ( total and non-SHBG-T ) was positively related with muscle strength and total body BMD ( for non-SHBG-T , respectively , beta = 1.93 + /- 0.52 , P < 0.001 and beta = 0.011 + /- 0.002 , P < 0.001 ) . An inverse association existed between T and fat mass ( beta = -0.53 + /- 0.15 , P < 0.001 ) . Non-SHBG-T and calc-FT were more strongly related to muscle strength , BMD , and fat mass than TT and were also significantly related to hip BMD . E1 and E2 were both positively , independently associated with BMD ( for E2 , beta = 0.21 + /- 0.08 , P < 0.01 ) . Non-SHBG-bound E2 was slightly strongly related to BMD than total E2 . The positive relation between T and BMD was independent of E2 . E1 and E2 were not related with muscle strength or body composition . In summary , bioavailable T , E1 , total E2 , and bioavailable E2 all decrease with age in healthy old men . In this cross-sectional study in healthy elderly men , non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T , which seems to play a direct role in the various physiological changes that occur during aging . A positive relation with muscle strength and BMD and a negative relation with fat mass was found . In addition , both serum E1 and E2 seem to play a role in the  age-related bone loss in elderly men , although the cross-sectional nature of the study precludes a definitive conclusion . Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD Long-term glucocorticoid therapy  in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone . We tested the effect of two and rogens , testosterone and its minimally aromatizable analog n and rolone , on muscle mass ( dual x-ray absorptiometry ) , muscle strength ( knee flexion and extension by isokinetic dynamometry ) , bone mineral density ( BMD ) , and quality of life ( Qualeffo-41 question naire ) in 51 men on a mean daily prednisone dose of 12.6 + /- 2.2 mg . Men were r and omized , double blind , to testosterone ( 200 mg mixed esters ) , n and rolone decanoate ( 200 mg ) , or placebo given every fortnight by i m injection for 12 months . At 12 months , both and rogens increased muscle mass ( mean change from baseline + 3.5 % , + 5.8 % , and -0.9 % in testosterone , n and rolone , and placebo groups , respectively , P < 0.0001 ) and muscle strength ( P < 0.05 ) . Lumbar spine BMD increased significantly only in men treated with testosterone ( 4.7 + /- 1.1 % , P < 0.01 ) . There was no significant change in hip or total body BMD . Testosterone , but not n and rolone or placebo , improved overall quality of life ( P < 0.001 ) . These results suggest that and rogen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for and rogen action on bone but not on muscle Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months .  Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) .  Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have  serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy OBJECTIVES To investigate the effects of testosterone supplementation on bone , body composition , muscle , physical function , and safety in older men . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING A major medical institution . PARTICIPANTS One hundred thirty-one men ( mean age 77.1 + /- 7.6 ) with low testosterone , history of fracture , or bone mineral density ( BMD ) T-score less than -2.0 and frailty . INTERVENTION Participants received 5 mg/d of testosterone or placebo for 12 to 24 months ; all received calcium ( 1500 mg/d diet and supplement ) and cholecalciferol ( 1,000 IU/d ) . MEASUREMENTS BMD of hip , lumbar spine , and mid-radius ; body composition ; sex hormones , calcium-regulating hormones ; bone turnover markers ; strength ; physical performance ; and safety parameters . RESULTS Ninety-nine men ( 75.6 % ) completed 12 months , and 62 ( 47.3 % ) completed end therapy ( mean 23 months ; range 16 - 24 months for 62 who completed therapy ) . Study adherence was 54 % , with 40 % of subjects maintaining 70 % or greater adherence . Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL , respectively , in the treatment group . BMD on testosterone  increased 1.4 % at the femoral neck and 3.2 % at the lumbar spine ( P=.005 ) and decreased 1.3 % at the mid-radius ( P<.001 ) . There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance . There were no differences in safety parameters . CONCLUSION Older , frail men receiving  testosterone replacement increased testosterone levels and had favorable changes in body composition , modest changes in axial BMD , and no substantial changes in physical function Summary We present results of a r and omized , placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density ( BMD ) , bone metabolism and body composition in 225 healthy adults aged 55 to 85 years . Introduction Dehydroepi and rosterone ( DHEA ) levels decline dramatically with age , concurrent with the onset of osteoporosis , suggesting a role for DHEA supplementation in preventing age-related bone loss . Methods We conducted a r and omized , placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density ( BMD ) , bone metabolism and body composition in 225 healthy adults aged 55 to 85 years . Results DHEA treatment increased serum DHEA and DHEA sulfate levels to concentrations seen in young adults . Testosterone , estradiol and insulin-like growth factor ( IGF-1 ) levels increased in women ( all p < 0.001 ) , but not men , receiving DHEA .  Serum C-terminal telopeptide of type-1 collagen levels decreased in women ( p = 0.03 ) , but not men , whereas bone-specific alkaline phosphatase levels were not significantly altered in either sex . After 12 months , there was a positive effect of DHEA on lumbar spine BMD in women ( p = 0.03 ) , but no effect was observed for hip , femoral neck or total body BMD , and no significant changes were observed at any site among men . Body composition was not affected by DHEA treatment in either sex . Conclusion Among older healthy adults , daily administration of 50 mg of DHEA has a modest and selective beneficial effect on BMD and bone resorption in women , but provides no bone benefit for men Aging in men is associated with loss of bone mass , impaired physical function and altered body composition . The objective of this proof‐of‐concept r and omized , double‐blind , placebo‐controlled , parallel‐group , single‐center trial was to determine the relative effects of testosterone ( T ) and estradiol ( E2 ) on bone mineral density , body composition , and physical performance in older men . The primary outcome was lumbar spine bone mineral density ( BMD ) , and secondary outcomes were body composition , muscle strength , gait speed , and sex hormone concentrations . Forty three men ( age range , 65–82 years ; mean age 71 years ) with low total T levels < 350 ng/dL were r and omized to one of three groups : 5 g transdermal testosterone gel ( TT ) ( N = 16 ) , anastrozole ( AI ) 1 mg ( N = 14 ) or placebo daily ( N = 13 ) for 12 months . Outcomes were assessed at baseline , 3 , 6 , and 12 months . Both TT and AI increased serum TT levels ( > 500 ng/dL , p < 0.05 ) compared to baseline ; T values remained stable throughout the duration of the trial . At 12 months , TT improved the primary outcome of lumbar spine BMD ( p < 0.01).Both interventions improved knee strength at 12 months compared to baseline ( p < 0.05 ) while lean body mass significantly increased only in the AI group at 6 and 12 months ( 1.49 ± 0.38 kg , p < 0.01 ; 1.24 ± 0.39 kg , p < 0.05 , respectively ) compared to baseline . Interestingly , TT improved fast gait speed at 3 and 12 months ( p < 0.01 , p < 0.05 , respectively ) . In summary , this proof‐of‐concept study confirms that aromatization of T is required for maintaining BMD in older men with low‐T levels . The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed , an observation that needs to be verified in future studies BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone  ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p < .002 ) at 12 months in the testosterone group , whereas no change occurred in the control group . Although there was no change in estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p < .017 ) . The testosterone group had a 0.3 % gain in femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia CONTEXT And rostenedione , a precursor to testosterone , is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use . However , whether and rostenedione actually increases blood testosterone levels or produces anabolic and rogenic effects is not known . OBJECTIVES To determine if short- and long-term oral and rostenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function . DESIGN AND SETTING Eight-week r and omized controlled trial conducted between February and June 1998 . PARTICIPANTS Thirty healthy , normotestosterogenic men ( aged 19 - 29 years ) not taking any nutritional supplements or and rogenic-anabolic steroids or engaged in resistance training . INTERVENTIONS Twenty subjects performed 8 weeks of whole-body resistance training . During weeks 1 , 2 , 4 , 5 , 7 , and 8 , the men were r and omized to either and rostenedione , 300 mg/d ( n = 10 ) , or placebo ( n = 10 ) . The effect of a single 100-mg and rostenedione dose on serum testosterone and estrogen concentrations was determined in 10 men . MAIN OUTCOME MEASURES Changes in serum testosterone and estrogen concentrations , muscle strength , muscle fiber cross-sectional area , body composition , blood lipids , and liver transaminase activities based on assessment s before and after short- and long-term and rostenedione administration . RESULTS Serum free and total testosterone concentrations were not affected by short- or long-term and rostenedione administration . Serum estradiol concentration ( mean [ SEM ] ) was higher ( P<.05 ) in the and rostenedione group after 2 ( 310 [ 20 ] pmol/L ) , 5 ( 300 [ 30 ] pmol/L ) , and 8 ( 280 [ 20 ] pmol/L ) weeks compared with presupplementation values ( 220 [ 20 ] pmol/L ) . The serum estrone concentration was significantly higher ( P<.05 ) after 2 ( 153 [ 12 ] pmol/L ) and 5 ( 142 [ 15 ] pmol/L ) weeks of and rostenedione supplementation compared with baseline ( 106 [ 11 ] pmol/L ) . Knee extension strength increased significantly ( P<.05 ) and similarly in the placebo ( 770 [ 55 ] N vs 1095 [ 52 ] N ) and and rostenedione ( 717 [ 46 ] N vs 1024 [ 57 ] N ) groups . The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in and rostenedione ( 4703 [ 471 ] vs 5307 [ 604 ] mm2 ; P<.05 ) and placebo ( 5271 [ 485 ] vs 5728 [ 451 ] mm2 ; P<.05 ) groups . The significant ( P<.05 ) increases in lean body mass and decreases in fat mass were also not different in the and rostenedione and placebo groups . In the and rostenedione group , the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks ( 1.09 [ 0.08 ] mmol/L [ 42 ( 3 ) mg/dL ] vs 0.96 [ 0.08 ] mmol/L [ 37 ( 3 ) mg/dL ] ; P<.05 ) and remained low after 5 and 8 weeks of training and supplementation . CONCLUSIONS And rostenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone < 10 nmol/L or free and rogen index < 30 % ) . Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD Abstract Objective To study the effect of 14 weeks of electromyostimulation ( EMS ) training ( 47 minutes/day , 5 days/week ) on both muscle and bone loss prevention in persons with recent , complete spinal cord injury ( SCI ) . Design Prospect i ve , experimental , controlled , single-blind r and omized trial with external blind evaluation by third parties . Methods Eight men with recent SCI ( 8 weeks from injury ; ASIA Impairment Scale ( AIS ) “ A ” ) were r and omized into the intervention or the control groups . Cross-sectional area of the quadriceps femoris ( QF ) muscle was quantified using magnetic resonance imaging .  Bone mineral density changes were assessed with a dual-energy X-ray absorptiometry . Several bone biomarkers ( i.e. total testosterone , cortisol , growth hormone , insulin-growth factor I , osteocalcin , serum type I collagen C-telopeptide ) , lipid , and lipoprotein profiles were quantified . A st and ard oral glucose tolerance test was performed before and after the 14-week training . All analyses were conducted at the beginning and after the intervention . Results The intervention group showed a significant increase in QF muscle size when compared with the control group . Bone losses were similar in both groups . Basal levels of bone biomarkers did not change over time . Changes in lipid and lipoprotein were similar in both groups . Glucose and insulin peaks moved forward after the training in the intervention group . Conclusions This study indicates that skeletal muscle of patients with complete SCI retains the ability to grow in response to a longitudinal EMS training , while bone does not respond to similar external stimulus . Increases in muscle mass might have induced improvements in whole body insulin-induced glucose uptake BACKGROUND Loss of muscle mass ( sarcopenia ) leads to frailty in older men . The decline in testosterone over the life span may contribute to this muscle loss . We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period . METHODS A st and ard dose ( 80 mg twice daily ) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older . All men had a free testosterone index of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . Measurements of body composition , muscle strength , hormones , and safety parameters were obtained at 0 , 6 , and 12 months . RESULTS Lean body mass increased ( p = .0001 ) and fat mass decreased ( p = .02 ) in the testosterone as compared with the placebo-treated group . There were no significant effects on muscle strength . There was a significant increase in hematocrit ( 0.02 % ) in the testosterone-treated group ( p = .03 ) . Plasma triglycerides , total cholesterol , and low-density lipoprotein cholesterol levels were similar in both groups , but there was a decrease in high-density lipoprotein cholesterol ( -0.1 mmol/L ) at 12 months in the testosterone group as compared to the placebo group ( p = 0.026 ) . There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups . CONCLUSION Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat Male osteoporosis is an important disease , with 25 - 30 % of all hip fractures occurring in men . In a recent r and omized , placebo-controlled study of osteoporotic males , alendronate 10 mg daily for 2 yr led to significant increments in bone mineral density ( BMD ) , of a similar magnitude to those observed in postmenopausal women . In this study , specimens collected at intervals during the recent trial of alendronate in male osteoporosis , from 197 of the original 241 participants , were assayed for testosterone , estradiol , IGF-I , IGF binding protein 3 ( IGFBP-3 ) , bone-specific alkaline phosphatase [ BSAP ( serum ) ] , and N-telopeptide of type I collagen corrected for creatinine [ NTx ( urine ) ] . Together with fracture and densitometry data from the original study , relationships were examined between BMD and serum IGF-I , IGFBP-3 , testosterone , estradiol , BSAP , and urine NTx , both at baseline and during treatment with alendronate , to gain possible insights into the pathogenesis of male osteoporosis . Statistically significant ( P < or= 0.05 ) associations were documented , at baseline , between the presence of vertebral fracture and each of serum IGF-I , serum IGFBP-3 , serum free testosterone , total spine BMD , and total body BMD . No statistically significant correlations were observed between any of the baseline variables ( IGF-I , IGFBP-3 , estradiol , testosterone , and presence of vertebral fracture ) and the BMD response to alendronate at any site . In a multivariate analysis , used to identify possible combinations of factors capable of predicting baseline BMD or response to alendronate , statistically significant ( P < or= 0.01 ) relationships were seen , at baseline , between BMD and body mass index , age , and prior fracture . However , no statistically significant relationships were seen between any of the baseline variables ( age , body mass index , testosterone , estradiol , IGF-I , IGFBP-3 , and prior fracture ) and change in BMD at any site . These data suggest that among men with osteoporosis it is not possible to identify patients who would be particularly good c and i date s for therapy with alendronate on the basis of biochemical or hormonal markers . Alendronate therapy appears to benefit osteoporotic males equally , irrespective of baseline serum testosterone , estradiol , IGF-I , or markers of bone turnover CONTEXT Cycling and rogens has been reported by athletes to improve physical performance by enhancing muscle mass and strength , a paradigm that has not been studied , and may have clinical value in older men being treated with testosterone .  OBJECTIVE We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current st and ard of care continuous therapy on body composition and muscle strength in older men . DESIGN , SETTING , AND PATIENTS Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were r and omized at the Institute for Translational Sciences- Clinical Research Center into a 5-month double-blind placebo-controlled trial . INTERVENTION Subjects were dosed weekly for 5 months , receiving continuous testosterone ( TE , n = 8 ; 100 mg testosterone enanthate , i m injection ) , monthly cycled testosterone ( MO , n = 8 ; alternating months of testosterone and placebo ) , or placebo ( PL , n = 8) . MAIN OUTCOME MEASURES Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength . Secondary outcomes included body weight , serum hormones , and mixed-muscle protein fractional synthesis rate ( FSR ) . RESULTS Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO ( P < 0.05 ) . Upper body muscle strength increased in TE , and lower body muscle strength increased in TE and MO ( P < 0.05 ) . FSR increased in TE and MO ( P < 0.05 ) but not in PL . CONCLUSIONS Cycled testosterone  improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone The cardiovascular effects of testosterone treatment are debated . Osteoprotegerin ( OPG ) is an independent marker of cardiovascular risk . We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels . A r and omized , double-blinded , placebo-controlled study of 6 months testosterone therapy ( gel )  in 38 men aged 60 - 78 years with bioavailable testosterone < 7.3 nmol/l and waist circumference > 94 cm was performed .  Clinical evaluation , OPG , and C-reactive protein ( CRP ) measurements were carried out . Lean body mass ( LBM ) , total fat mass , and bone mineral density ( BMD ) were established by dual X-ray absorptiometry . Visceral adipose tissue ( VAT ) and subcutaneous adipose tissue ( SAT ) were measured by magnetic resonance imaging . Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM ( Δ LBM positive ) , n=14 . Data are presented as median ( interquartile range ) . Testosterone therapy  decreased total fat mass and SAT , whereas VAT was unchanged ( n=38 ) . OPG levels decreased during testosterone therapy ( from 2.0 ( 1.9 - 2.5 ) to 1.9 ( 1.6 - 2.2 ) ng/ml , p<0.05 vs. placebo ) , whereas CRP levels were unchanged ( n=38 ) . In responders to testosterone therapy ( n=14 ) , ΔOPG levels were inversely associated with ΔSAT ( r= - 0.60 , p=0.03 ) and positively associated with ΔVAT ( r=0.56 , p=0.04 ) . OPG levels  decreased during testosterone therapy suggesting decreased cardiovascular risk . Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution Treatment of hypogonadal men with testosterone  has been shown to ameliorate the effects of testosterone deficiency on bone , muscle , erythropoiesis , and the prostate . Most previous studies , however , have employed somewhat pharmacological doses of testosterone esters , which could result in exaggerated effects , and /or have been of relatively short duration or employed previously treated men , which could result in dampened effects . The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density , muscle mass and strength , erythropoiesis , prostate volume , energy , sexual function , and lipids in previously untreated hypogonadal men . We selected 18 men who were hypogonadal ( mean serum testosterone + /- SD , 78 + /- 77 ng/dL ; 2.7 + /- 2.7 nmol/L ) due to organic disease and had never previously been treated for hypogonadism . We treated them with testosterone transdermally for 3 yr . Sixteen men completed 12 months of the protocol , and 14 men completed 36 months . The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment . Bone mineral density of the lumbar spine ( L2-L4 ) increased by 7.7 + /- 7.6 % ( P < 0.001 ) , and that of the femoral trochanter increased by 4.0 + /- 5.4 % ( P = 0.02 ) ; both reached maximum values by 24 months . Fat-free mass increased 3.1 kg ( P = 0.004 ) , and fat-free mass of the arms and legs individually increased , principally within the first 6 months . The decrease in fat mass was not statistically significant . Strength of knee flexion and extension did not change . Hematocrit increased dramatically , from mildly anemic ( 38.0 + /- 3.0 % ) to midnormal ( 43.1 + /- 4.0 % ; P = 0.002 ) within 3 months , and remained at that level for the duration of treatment . Prostate volume also increased dramatically , from subnormal ( 12.0 + /- 6.0 mL ) before treatment to normal ( 22.4 + /- 8.4 mL ; P = 0.004 ) , principally during the first 6 months . Self-reported sense of energy ( 49 + /- 19 % to 66 + /- 24 % ; P = 0.01 ) and sexual function ( 24 + /- 20 % to 66 + /- 24 % ; P < 0.001 ) also increased , principally within the first 3 months . Lipids did not change . We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip , fat-free mass , prostate volume , erythropoiesis , energy , and sexual function . The full effect of testosterone on bone mineral density took 24 months , but the full effects on the other tissues took only 3 - 6 months . These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men Estrogen ( E ) deficiency associated with the menopause is the major cause of bone loss in aging women . However , men also lose significant amounts of bone with age , but they do not have the equivalent of menopause , and serum total testosterone ( T ) and E levels decline only marginally with age in men . Thus , it has been difficult to attribute bone loss in aging men to either T or E deficiency . Here , we show in a population -based , age-stratified sample of 346 men , aged 23 - 90 yr , that serum total T and E ( estradiol plus estrone ) levels decreased over the life span by 30 % and 12 % , respectively , but bioavailable ( or nonsex hormone-binding globulin-bound ) T and E levels decreased by 64 % and 47 % , respectively . In these men and in a parallel cohort of 304 women , aged 21 - 94 yr , serum PTH increased 84 % and 64 % over the life span , and urinary N-telopeptide of type I collagen ( NTx ) excretion , a bone resorption marker , increased 77 % and 80 % between age 50 - 85 yr in the men and women , respectively . By univariate analyses , serum bioavailable T and E levels correlated positively with bone mineral density ( BMD ) at the total body , spine , proximal femur , and distal radius and negatively with urinary NTx excretion in men and women . Urinary NTx excretion was also negatively associated with BMD in both sexes . By multivariate analyses , however , serum bioavailable E level was the consistent independent predictor of BMD in both men and postmenopausal women . Thus , bioavailable E levels decline significantly with age and are important predictors of BMD in men as well as women . These studies suggest that in contrast to traditional belief , age-related bone loss may be the result of E deficiency not just in postmenopausal women , but also in 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 BACKGROUND Data on the influence of gonadal hormones on incident fracture risk in elderly men are limited . We prospect ively examined the relationship between serum levels of testosterone and estradiol and future fracture risk in community-dwelling men . METHODS A total of 609 men older than 60 years had been observed between January 1989 and December 2005 , with the median duration being 5.8 years ( up to 13 years ) . Clinical risk factors , including bone mineral density and lifestyle factors , were assessed at baseline .  Serum testosterone and estradiol levels were measured by t and em mass spectrometry . The incidence of a low-trauma fracture was ascertained during follow-up . RESULTS During follow-up , 113 men had at least 1 low-trauma fracture . The risk of fracture was significantly increased in men with reduced testosterone levels ( hazard ratio [ HR ] , 1.33 ; 95 % confidence interval [ CI ] , 1.09 - 1.62 ) . After adjustment for sex hormone-binding globulin , serum testosterone ( HR , 1.48 ; 95 % CI , 1.22 - 1.78 ) and serum estradiol ( HR , 1.21 ; 95 % CI , 1.00 - 1.47 ) levels were associated with overall fracture risk . After further adjustment for major risk factors of fractures ( age , weight or bone mineral density , fracture history , smoking status , calcium intake , and sex hormone-binding globulin ) , lower testosterone was still associated with increased risk of fracture , particularly with hip ( HR , 1.88 ; 95 % CI , 1.24 - 2.82 ) and nonvertebral ( HR , 1.32 ; 95 % CI , 1.03 - 1.68 ) fractures . CONCLUSION In community-dwelling men older than 60 years , serum testosterone is independently associated with the risk of osteoporotic fracture and its measurement may provide additional clinical information for the assessment of fracture risk in elderly men This study examines the effects of 32 weeks of exercise training on balance , lower-extremity muscle strength , bone mineral density ( BMD ) and serum levels of bone metabolism and inflammatory markers in older adults . Forty-seven healthy older adults ( women=24 , men=23 ; mean age 68.2 years ) participated in a exercise intervention ( 60min/session ) that included resistance exercise training ( 2 days/week ) at 75 - 80 % of maximum plus a multicomponent weight-bearing impact exercise training ( 1 day/week ) . Outcome measures included lumbar spine and proximal femoral BMD , dynamic balance , muscle strength , serum levels of bone metabolism markers [ osteocalcin ( OC ) , C-terminal telopeptide of Type I collagen ( CTX ) , osteoprotegerin ( OPG ) and receptor activator of nuclear factor kappa B lig and ( RANKL ) ] and serum levels of inflammatory markers [ high sensitive (hs)-C-reactive protein ( CRP ) , interleukin (IL)-6 , tumor necrosis factor (TNF)-α , and interferon (IFN)-γ ] . Potential confounding variables included body composition , dietary intake ( using 4-day diet records ) , and accelerometer-based physical activity . After 32 weeks , both men and women increased dynamic balance ( 6.4 % ) , muscle strength ( 11.0 % ) and trochanter ( 0.7 % ) , intertrochanter ( 0.7 % ) , total hip ( 0.6 % ) , and lumbar spine BMD ( 1.7 % ) , while OC , CTX , OPG and RANKL levels remained unchanged . In addition , hs-CRP and IFN-γ levels were decreased , while TNF-α levels were unchanged , and a decrease in IL-6 levels was only observed in men . These findings suggest that our combined impact protocol reduces inflammation and increases BMD , balance , and lower-extremity muscle strength , despite having little effect on bone metabolism markers . This reinforces the role of exercise to counteract the age-related inflammation , and the muscle strength , balance and BMD reduction PURPOSE And rogen deprivation therapy is associated with fracture risk in men with prostate cancer . We assessed the effects of toremifene , a selective estrogen receptor modulator , on fracture incidence in men receiving and rogen deprivation therapy  during a 2-year period . MATERIAL S AND METHODS In this double-blind , placebo controlled phase III study 646 men receiving and rogen deprivation therapy for prostate cancer were assigned to toremifene ( 80 mg by mouth daily ) and 638 were assigned to placebo . Subjects were followed for 2 years . The primary study end point was new vertebral fractures . Secondary end points included fragility fractures , bone mineral density and lipid changes . RESULTS The 2-year incidence of new vertebral fractures was 4.9 % in the placebo group vs 2.5 % in the toremifene group , a significant relative risk reduction of 50 % ( 95 % CI -1.5 to 75.0 , p = 0.05 ) . Toremifene significantly increased bone mineral density at the lumbar spine , hip and femoral neck vs placebo ( p < 0.0001 for all comparisons ) . There was a concomitant decrease in markers of bone turnover ( p < 0.05 for all comparisons ) . Toremifene also significantly improved lipid profiles . Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects ( 1.1 % ) in the placebo group experiencing a venous thromboembolic event vs 17 ( 2.6 % ) in the toremifene group . Other adverse events were similar between the groups . CONCLUSIONS Toremifene significantly decreased the incidence of new vertebral fractures in men receiving and rogen deprivation therapy for prostate cancer . It also significantly improved bone mineral density , bone turnover markers and serum lipid profiles There are few reported data on biochemical and functional correlates of and rogen levels in African-American men . This study aim ed at reporting physical and biochemical correlates of serum total testosterone ( total T ) , bioavailable testosterone ( BT ) and dehydroepi and rosterone-sulphate ( DHEAS ) levels in community-dwelling , African-American men aged 50 - 65 years .  Home-based physical examinations and health status question naires were administered to r and omly sample d men .  Body composition ( dual-energy X-ray absorptiometry ) , lower limb and h and -grip muscle strength , and neuropsychological functions were assessed . Levels of serum total T , BT , DHEAS , oestradiol ( E2 ) , adiponectin , leptin , triglycerides and glucose were measured . Multiple linear regression models were constructed to identify factors independently associated with and rogen levels . DHEAS levels declined from age 50 to 65 years ( p < 0.0001 ) , but total T and BT levels remained constant . Independent of other associated factors , higher total T levels were associated with lower serum triglyceride levels ( beta = -0.142 , p = 0.049 ) ; higher BT was associated with better performance on the trail-making tests ( TMT-B : TMT-A ratio : beta = -0.118 , p = 0.024 ) and higher DHEAS levels were associated with lower adiponectin ( beta = -0.293 , p = 0.047 ) and higher mini-mental state examination ( MMSE ) score ( beta = 0.098 , p = 0.008 ) . Multiple regression models predicted 21 , 18 and 29 % of variance in total T , BT and DHEAS , respectively . Higher total T levels were associated with serum metabolic markers , particularly lower triglycerides , whereas higher BT was associated with better cognitive and muscle function and DHEAS with lower adiponectin and higher MMSE scores 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 We investigated the effects of 6 mo of near-physiological testosterone administration  to older men on skeletal muscle function and muscle protein metabolism .  Twelve older men ( > or = 60 yr ) with serum total testosterone concentrations < 17 nmol/l ( 480 ng/dl ) were r and omly assigned in double-blind manner to receive either placebo ( n = 5 ) or testosterone enanthate ( TE ; n = 7 ) injections . Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point . TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l . Lean body mass ( LBM ) , muscle volume , prostate size , and urinary flow were measured at baseline and at 6 mo . Protein expression of and rogen receptor ( AR ) and insulin-like growth factor I , along with muscle strength and muscle protein metabolism , were measured at baseline and at 1 and 6 mo of treatment . Hematological parameters were followed monthly throughout the study . Older men receiving  testosterone increased total and leg LBM , muscle volume , and leg and arm muscle strength after 6 mo . LBM accretion result ed from an increase in muscle protein net balance , due to a decrease in muscle protein breakdown . TE treatment increased expression of AR protein at 1 mo , but expression returned to pre-TE treatment levels by 6 mo . IGF-I protein expression increased at 1 mo and remained increased throughout TE administration . We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength OBJECTIVE Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome ( PCOS ) . In addition , whether lean mass influences carotid intima-media thickness ( IMT ) in PCOS has not been assessed . DESIGN Prospect i ve investigation . METHODS Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls . All women had dual X-ray absorptiometry for lean , fat and bone mass  , and bone mass density ( BMD )  . Serum testosterone , sex hormone-binding globulin , insulin , and glucose and carotid IMT  were determined . Free and rogen index ( FAI ) and insulin resistance ( by QUICKI ) were calculated . RESULTS In PCOS , waist circumference and insulin were higher and QUICKI lower than in controls ( P<0.01 ) . Trunk fat mass , % trunk fat , and lean mass were higher in PCOS compared to controls ( P<0.01 ) , while total bone mass and BMD were similar . IMT was increased in PCOS ( P<0.01 ) but only 15 % of PCOS patients had abnormal ( > or = 0.9 mm ) values . Lean mass correlated with fat parameters , insulin , QUICKI , and FAI , but not with total testosterone ; and after adjustments for insulin and QUICKI , lean mass still correlated with fat mass ( P<0.01 ) but not FAI . Lean mass correlated with IMT ( P<0.01 ) , but this was dependent on insulin . However , excluding those patients with abnormal IMT values , IMT correlated with lean mass independently of insulin . Bone mass correlated with lean and fat mass , but not with insulin or and rogen . PCOS patients with ' pathological ' IMT values had higher % trunk fat , lean mass , and insulin , lower QUICKI , and higher testosterone and FAI compared with those with normal IMT . CONCLUSION Lean mass is increased in PCOS , while bone mass is similar to that of matched controls . The major correlates of lean mass are fat mass and insulin but not and rogen . Lean mass also correlated with IMT , and although influenced by insulin , small changes in IMT may partially reflect changes in muscle mass , while clearly abnormal values relate to more severe abnormalities of PCOS 10 . Nair N , Oka RK , Waring LD et al. Vascular compliance versus flow-mediated dilatation : correlation with cardiovascular risk factors . Vasc Med 2005 ; 10 : 275–83 . 11 . Wilkinson IB , MacCallum H , Cockcroft JR et al. Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo . Br J Clin Pharmacol 2002 ; 53 : 189–92 . 12 . Stewart AD , Millasseau SC , Kearney MT et al. Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans . Hypertension 2003 ; 42 : 915–8 . 13 . Bulpitt CJ , Rajkumar C , Cameron JD . Vascular compliance as a measure of biological age . J Am Geriatr Soc 1999 ; 47 : 657–63 . 14 . Rossouw JE . Risks and benefits of estrogen plus progestin in healthy postmenopausal women : principal results From the Women ’s Health Initiative r and omized controlled trial . JAMA 2002 ; 288 : 321–33 . 15 . Haddad RM , Kennedy CC , Caples SM et al.  Testosterone and cardiovascular risk in men : a systematic review and meta analysis of r and omized placebo-controlled trials . Mayo Clin Proc 2007 ; 82 : 29–39 . 16 . Lane HA , Grace F , Smith JC et al. Impaired vasoreactivity in bodybuilders using and rogenic anabolic steroids . Eur J Clin Invest 2006 ; 36 : 483–8 . 17 . McCredie RJ , McCrohon JA , Turner L et al. Vascular reactivity is impaired in genetic females taking high-dose and rogens . J Am Coll Cardiol 1998 ; 32 : 1331–5 . 18 . Ong PJL , Patrizi G , Chong WCF et al. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease . Am J Cardiol 2000 ; 85 : 269–72 . 19 . Dockery F , Bulpitt CJ , Agarwal S et al. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia . Clin Sci 2003 ; 104 : 195–201 . 20 . Swartz CM , Young MA . Low serum testosterone and myocardial infa rct ion in geriatric male in patients . J Am Geriatr Soc 1987 ; 35 : 39–44 . 21 . Phillips GB , Pinkernell BH , Jing TY . The association of hypotestosteronaemia with coronary artery disease in men . Arterioscler Thromb 1994 ; 14 : 701–6 . 22 . Webb CM , Elkington AG , Kraidly MM et al. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease . Am J Cardiol 2008 ; 101 : 618–24 , Epub 2007 Dec 21 . 23 . English KM , Steeds RP , Jones TH et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina : a r and omized , double-blind , placebocontrolled study . Circulation 2000 ; 102 : 1906–11 . 24 . Ishihara F , Hiramatsu K , Shigematsu S et al. Role of adrenal and rogens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta . Cardiology 1992 ; 80 : 332–8 . 25 . Hougaku H , Fleg JL , Najjar SS et al. Relationship between and rogenic hormones and arterial stiffness , based on longitudinal hormone measurements . Am J Physiol Endocrinol Metab 2006 ; 290 : E234–42 . 26 . Perheentupa A , Huhtaniemi I. Does the and ropause exist ? Nat Clin Pract Endocrinol Metab 2007 ; 3 : 670–1 . 27 . Emmelot-Vonk MH , Verhaar HJ , Nakhai Pour HR et al. Effect of testosterone supplementation on functional mobility , cognition , and other parameters in older men : a r and omized controlled trial . JAMA 2008 ; 299 : 39–52 . 28 . Isidori AM , Giannetta E , Greco EA et al. Effects of testosterone on body composition , bone metabolism and serum lipid profile in middle-aged men : a meta- analysis . Clin Endocrinol 2005 ; 63 : 280–93 The serum concentration of sex hormone-binding globulin ( SHBG ) is inversely related to weight and in animal studies is inversely related to protein intake . As SHBG can affect the biological activity of testosterone and estradiol , we wished to determine the role of protein intake on SHBG levels in men . Using data from the Massachusetts Male Aging Study we examined cross-sectional relationships between dietary components and SHBG levels in 1552 men ( aged 40 - 70 yr ) for whom these factors were known . Analyzed by multiple regression , controlling for testosterone and estradiol levels , age ( P<0.001 ) and fiber intake ( P = 0.02 ) were positively correlated to SHBG concentration , whereas body mass index ( P<0.001 ) and protein intake ( P<0.03 ) were negatively correlated to SHBG concentration . The intakes of calories , fat ( animal or vegetable ) , and carbohydrate were not related to SHBG concentration . We conclude that age and body mass index are major determinants of SHBG concentrations in older men , and fiber and protein intake are also significant contributors to SHBG levels , but total caloric intake and the intake of carbohydrate or fat are not significant . Thus , diets low in protein in elderly men may lead to elevated SHBG levels and decreased testosterone bioactivity . The decrease in bioavailable testosterone can then result in declines in sexual function and muscle and red cell mass , and contribute to the loss of bone density PURPOSE In a recently completed 3-year , r and omized , double-blind study , denosumab , a fully human monoclonal antibody against receptor activator of nuclear factor kappaB lig and , significantly increased bone mineral density and decreased new vertebral fractures in men receiving and rogen deprivation therapy for prostate cancer . We conducted subgroup analyses to evaluate the relationships between subject characteristics and the effects of denosumab on bone mineral density at multiple skeletal sites . MATERIAL S AND METHODS A total of 1,468 subjects were r and omized 1:1 to receive 60 mg subcutaneous denosumab every 6 months or  placebo  for 36 months . In these analyses we evaluated the effects of denosumab on bone mineral density at the lumbar spine , total hip and distal 1/3 radius ( sub study of 309 subjects ) during 36 months in specific subgroups according to age , duration and type of prior and rogen deprivation therapy , bone mineral density T score , weight , body mass index , bone turnover marker levels and prevalent vertebral fractures . RESULTS After 36 months denosumab significantly increased bone mineral density of the lumbar spine , total hip and distal 1/3 radius by 7.9 % , 5.7 % and 6.9 % , respectively , compared with placebo ( p < 0.0001 for each comparison ) . Denosumab significantly increased bone mineral density to a degree similar to that observed in the overall analysis for every subgroup including older men as well as those with prevalent fractures , lower baseline bone mineral density , and higher serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b . Mean increases in bone mineral density at each skeletal site were greatest for men with the highest levels of serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b . CONCLUSIONS Denosumab significantly and consistently increased bone mineral density at all skeletal sites and in every subgroup , including men at greatest risk for bone loss and fractures Objective . To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers , bone mineral density and body composition in oophorectomized women . Methods . Fifty women , 45–60 years old , who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders , were r and omly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily . Twenty-four weeks later , cross-over was performed to the other treatment regimen . Forty-four women completed the study . Their serum concentrations of insulin-like growth factor (IGF)-I , IGF binding protein (IGFBP)-3 , osteocalcin , carboxyterminal telopeptide aminoterminal ( ICTP ) , of type I collagen propeptide of type I procollagen ( PICP ) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments , as were also their body mass index ( BMI ) and blood pressure . Bone mineral density of the total body , spine and hip and total body fat , total lean body mass , trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens . Results . During treatment , the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone . Osteocalcin and ICTP were significantly reduced to the same extent by both therapies . No change ocurred in the IL-1 receptor antagonist . A significant increase was seen in total lean body mass with the estrogen/testosterone regimen , but the total fat mass , trunk lean or fat mass remained unchanged after 24 weeks of both treatments . No effect was detected on total , hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone . Likewise , BMI and blood pressure were unaffected . Conclusions . The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP levels . An anabolic effect on muscle was reflected by an increase in the total lean body mass . No adverse effects were noted on BMI , fat distribution or blood pressure during the 6-month treatment with oral testosterone undecanoate Testosterone increases muscle mass and strength and regulates other physiological processes , but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various and rogen-dependent processes are similar . To determine the effects of grade d doses of testosterone on body composition , muscle size , strength , power , sexual and cognitive functions , prostate-specific antigen ( PSA ) , plasma lipids , hemoglobin , and insulin-like growth factor I ( IGF-I ) levels , 61 eugonadal men , 18 - 35 yr , were r and omized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone ( GnRH ) agonist , to suppress endogenous testosterone secretion , and weekly injections of 25 , 50 , 125 , 300 , or 600 mg of testosterone enanthate for 20 wk . Energy and protein intakes were st and ardized . The administration of the GnRH agonist plus grade d doses of testosterone result ed in mean nadir testosterone concentrations of 253 , 306 , 542 , 1,345 , and 2,370 ng/dl at the 25- , 50- , 125- , 300- , and 600-mg doses , respectively . Fat-free mass increased dose dependently in men receiving 125 , 300 , or 600 mg of testosterone weekly ( change + 3.4 , 5.2 , and 7.9 kg , respectively ) . The changes in fat-free mass were highly dependent on testosterone dose ( P = 0.0001 ) and correlated with log testosterone concentrations ( r = 0.73 , P = 0.0001 ) . Changes in leg press strength , leg power , thigh and quadriceps muscle volumes , hemoglobin , and IGF-I were positively correlated with testosterone concentrations , whereas changes in fat mass and plasma high-density lipoprotein ( HDL ) cholesterol were negatively correlated . Sexual function , visual-spatial cognition and mood , and PSA levels did not change significantly at any dose . We conclude that changes in circulating testosterone concentrations , induced by GnRH agonist and testosterone administration , are associated with testosterone dose- and concentration-dependent changes in fat-free mass , muscle size , strength and power , fat mass , hemoglobin , HDL cholesterol , and IGF-I levels , in conformity with a single linear dose-response relationship . However , different and rogen-dependent processes have different testosterone dose-response relationships As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol .  Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer The consequences of GH deficiency may differ if the disease is childhood onset or adulthood onset . In this single-center , prospect i ve study , 21 consecutive adults with childhood onset GH deficiency and 21 adults with adulthood onset GH deficiency , matched for age , gender , body mass index , and number of anterior pituitary hormonal deficiencies , were included . Baseline differences and differences in the responses in body composition , muscle strength , bone mass , and metabolic indices during 5-yr GH replacement were determined . The duration of GH deficiency was longer and serum IGF-I level and body height were lower in the childhood onset patients than in the adulthood onset patients . Body fat ( observed/predicted ratio ) was increased , and lean mass and muscle strength were decreased , in the childhood onset patients . Total body and lumbar ( L2-L4 ) bone mineral content and bone mineral density were lower in the childhood onset patients . Serum total cholesterol level was higher in the adulthood onset patients . The childhood onset and adulthood onset patients received a similar dose of GH . After adjustment for body weight , however , the dose of GH was higher in the childhood onset patients . The treatment responses were more marked in the childhood onset patients in lean mass , knee extensor strength , left-h and grip strength , and in total body and lumbar ( L2-L4 ) bone mineral content and bone mineral density . The reduction in serum total cholesterol concentration was more marked in the adulthood onset patients . At study end , no differences remained between the two study groups after the correction for body height in the statistical analysis . In conclusion , the baseline analysis suggests more decreased lean mass , muscle strength , and bone mass in the childhood onset patients whereas the lipid profile was more disturbed in the adulthood onset patients . The 5-yr GH replacement eliminated all the anthropodometric and metabolic differences between the two groups 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 Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength . The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown . OBJECTIVE To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss . DESIGN AND SETTING Placebo-controlled , double-blind , r and omized clinical trial conducted from September 1995 to July 1998 at a general clinical research center . PARTICIPANTS Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L ( 349 ng/dL ) and weight loss of 5 % or more in the previous 6 months , 49 of whom completed the study . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : placebo , no exercise ( n = 14 ) ; testosterone enanthate ( 100 mg/wk intramuscularly ) , no exercise ( n = 17 ) ; placebo and exercise ( n = 15 ) ; or testosterone and exercise ( n = 15 ) . Treatment duration was 16 weeks . MAIN OUTCOME MEASURES Changes in muscle strength , body weight , thigh muscle volume , and lean body mass compared among the 4 treatment groups . RESULTS Body weight increased significantly by 2.6 kg ( P<.001 ) in men receiving testosterone alone and by 2.2 kg ( P = .02 ) in men who exercised alone but did not change in men receiving placebo alone ( -0.5 kg ; P = .55 ) or testosterone and exercise ( 0.7 kg ; P = .08 ) . Men treated with testosterone alone , exercise alone , or both experienced significant increases in maximum voluntary muscle strength in leg press ( range , 22%-30 % ) , leg curls ( range , 18%-36 % ) , bench press ( range , 19%-33 % ) , and latissimus pulls ( range , 17%-33 % ) . Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group . There was a greater increase in thigh muscle volume in men receiving testosterone alone ( mean change , 40 cm3 ; P<.001 vs zero change ) or exercise alone ( 62 cm3 ; P = .003 ) than in men receiving placebo alone ( 5 cm3 ; P = .70 ) . Average lean body mass increased by 2.3 kg ( P = .004 ) and 2.6 kg ( P<.001 ) , respectively , in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone ( 0.9 kg ; P = .21 ) . Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo . CONCLUSION Our data suggest that testosterone and resistance exercise promote gains in body weight , muscle mass , muscle strength , and lean body mass in HIV-infected men with weight loss and low testosterone levels . Testosterone and exercise together did not produce greater gains than either intervention alone Several r and omized trials of and rogen supplementation in older men have been undertaken . However , the relative contributions of testosterone ( T ) and estrogens on bone metabolism in aging men are controversial . Within the setting of two double-blind , placebo-controlled studies , we evaluated the effect of dihydrotestosterone ( DHT ) and recombinant human chorionic gonadotropin ( rhCG ) on bone turnover in healthy , community-dwelling older men with partial and rogen deficiency ( total T < or = 15 nmol/liter ) . In the first study , 35 men ( age 68.3 + /- 6.8 yr ; baseline T , 13.9 + /- 3.3 nmol/liter ) were r and omized to receive either daily transdermal DHT ( n = 17 ) or placebo for 3 months . In the second study , 40 men ( age 67.4 + /- 5.4 yr ; baseline T , 11.4 + /- 2.2 nmol/liter ) were r and omized to receive either rhCG s.c . ( n = 20 ) , two injections weekly , or placebo for 3 months . The following parameters were measured before , monthly during , and 1 month after treatment : serum T , estradiol ( E2 ) , and LH ; markers of bone formation , serum amino-terminal propeptide of type I procollagen ( S-PINP ) and osteocalcin ; markers of bone resorption , serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline . Compared with placebo , treatment with DHT significantly increased serum DHT and suppressed LH and T levels , whereas E2 concentrations and markers of bone turnover did not change . In contrast , rhCG therapy significantly increased both T and E2 , with the increases in E2 being supraphysiological . At the same time , rhCG significantly increased S-PINP concentrations with peak levels after 1 month ( Delta40 % ; P = 0.02 compared with placebo ) . In contrast , serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change . The change in S-PINP levels correlated with the change in E2 levels ( r = 0.59 ; P = 0.02 ) but not with a change in T. We conclude that in older men with partial age-related and rogen deficiency , rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption . In contrast , treatment with a pure , nonaromatizable and rogen ( DHT ) has no effect on bone turnover despite a 20-fold increase in serum levels . Bone resorption was not accelerated during unchanged ( DHT ) or increased ( rhCG ) E2 levels , suggesting that minimal E2 levels are needed to maintain stable resorption , although direct and rogen receptor-mediated effects can not be excluded . If and rogen supplementation is required for aging men , aromatizable and rogens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone
The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men .
OBJECTIVES Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass , accumulation of central adiposity , impaired mobility and increased risk of bone fractures .
Whether and rogen treatment might be beneficial in these subjects is still under debate .
We have carried out a systematic review of r and omized controlled trials ( RCTs ) evaluating the effects of testosterone ( T ) administration  to middle-aged and ageing men on body composition , muscle strength , bone density , markers of bone metabolism and serum lipid profile .