Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism 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. 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. Prevalence of symptomatic androgen deficiency in men. Effects of testosterone supplementation in the aging male. Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Testosterone therapy increases sexual desire in ageing men with low–normal testosterone levels and symptoms of androgen deficiency Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly 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 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 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 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 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 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 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 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 And rogen therapy may precipitate  obstructive sleep apnea in men . Despite increasing and rogen use in older men , few studies have examined sleep and breathing . R and omized , double-blind , placebo-controlled studies examining effects of testosterone simultaneously on sleep , breathing , and function in older men are not available . Seventeen community-dwelling healthy men over the age of 60 yr were r and omized to receive three injections of i m testosterone esters at weekly intervals ( 500 mg , 250 mg , and 250 mg ) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout .  Polysomnography , anthropometry , and physical , mental , and metabolic function were assessed at baseline and after each treatment period . Testosterone treatment reduced total time slept ( approximately 1 h ) , increased the duration of hypoxemia ( approximately 5 min/night ) , and disrupted breathing during sleep ( total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour ) ( all P < 0.05 ) . Despite expected effects on body composition ( increase in total and lean mass , reduction in fat mass , P < 0.05 , bioimpedance method ) , upper airway dimensions did not change ( acoustic reflectometry ) . Driving ability ( computer simulation ) , physical activity ( accelerometry , Physical Activity Scale in the Elderly ) , quality of life ( SF36 , Functional Outcomes of Sleep Question naire ) , mood ( Profile of Mood States Question naire ) , sleepiness ( Epworth , Stanford scales ) , and insulin resistance ( homeostasis model ) also were not changed by treatment . Short-term administration of high-dose testosterone  shortens sleep and worsens sleep apnea in older men but did not alter physical , mental , or metabolic function . These changes did not appear to be due to upper airway narrowing . Further study of longer-term lower-dose and rogen therapy on sleep and breathing is needed to evaluate its safety in older men 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 Postmenopausal women with elevated circulating and rogen concentrations have an increased risk of developing breast cancer , yet interventions to reduce and rogen levels have not been identified . We examined the effects of a 12-month moderate intensity exercise intervention on serum and rogens . The study was a r and omized clinical trial in 173 sedentary , overweight ( body mass index > or = 24.0 kg/m(2 ) , body fat > 33 % ) , postmenopausal women , ages 50 to 75 years , not using hormone therapy and living in the Seattle , WA area . The exercise intervention included facility-based and home-based exercise ( 45 minutes , 5 days per week of moderate intensity sports/recreational exercise ) . A total of 170 ( 98.3 % ) women completed the study , with exercisers averaging 171 minutes per week of exercise . Women in the exercise and control groups experienced similar , nonsignificant declines in most and rogens . Among women who lost > 2 % body fat , testosterone and free testosterone concentrations fell by 10.1 % and 12.2 % between baseline and 12 months in exercisers compared with a decrease of 1.6 % and 8.0 % in controls ( P = 0.02 and 0.03 compared with exercisers , respectively ) . Concentrations of testosterone and free testosterone among exercisers who lost between 0.5 % and 2 % body fat declined by 4.7 % and 10.4 % . In controls who lost this amount of body fat , concentrations of testosterone and free testosterone declined by only 2.8 % and 4.3 % ( P = 0.03 and 0.01 compared with exercisers , respectively ) . In summary , given similar levels of body fat loss , women r and omized to a 12-month exercise intervention had greater declines in testosterone and free testosterone compared with controls . The association between exercise and breast cancer risk may be partly explained by the effects of exercise on these hormones 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 To investigate the role of and rogens in increasing bone density and improving low libido in postmenopausal women , we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospect i ve , 2 year , single-blind r and omised trial . Thirty-four postmenopausal volunteers were r and omised to treatment with either estradiol implants 50 mg alone ( E ) or estradiol 50 mg plus testosterone 50 mg ( E&T ) , administered 3-monthly for 2 years . Cyclical oral progestins were taken by those women with an intact uterus . Thirty-two women completed the study .  BMD ( DEXA ) of total body , lumbar vertebrae ( L1-L4 ) and hip area increased significantly in both treatment groups . BMD increased more rapidly in the testosterone treated group at all sites . A substantially greater increase in BMD occurred in the E&T group for total body ( P < 0.008 ) , vertebral L1-L4 ( P < 0.001 ) and trochanteric ( P < 0.005 ) measurements . All sexual parameters ( Sabbatsberg sexual self-rating scale ) improved significantly in both groups . Addition of testosterone result ed in a significantly greater improvement compared to E for sexual activity ( P < 0.03 ) , satisfaction ( P < 0.03 ) , pleasure ( P < 0.01 ) , orgasm ( P < 0.035 ) and relevancy ( P < 0.05 ) . Total cholesterol and LDL-cholesterol fell in both groups as did total body fat . Total body fat-free mass ( DEXA , anthropometry , impedance ) increased in the E&T group only . We concluded that in postmenopausal women , treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone . Significantly greater improvement in sexuality was observed with combined therapy , verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women . The favourable estrogenic effects on lipids were preserved in women treated with T , in association with beneficial changes in body composition To investigate the role of and rogens in increasing bone density and improving low libido in postmenopausal women , we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospect i ve , 2 year , single-blind r and omised trial . Thirty-four postmenopausal volunteers were r and omised to treatment with either estradiol implants 50 mg alone ( E ) or estradiol 50 mg plus testosterone 50 mg ( E&T ) , administered 3-monthly for 2 years . Cyclical oral progestins were taken by those women with an intact uterus . Thirty-two women completed the study .  BMD ( DEXA ) of total body , lumbar vertebrae ( L1-L4 ) and hip area increased significantly in both treatment groups . BMD increased more rapidly in the testosterone treated group at all sites . A substantially greater increase in BMD occurred in the E&T group for total body ( P < 0.008 ) , vertebral L1-L4 ( P < 0.001 ) and trochanteric ( P < 0.005 ) measurements . All sexual parameters ( Sabbatsberg sexual self-rating scale ) improved significantly in both groups . Addition of testosterone result ed in a significantly greater improvement compared to E for sexual activity ( P < 0.03 ) , satisfaction ( P < 0.03 ) , pleasure ( P < 0.01 ) , orgasm ( P < 0.035 ) and relevancy ( P < 0.05 ) . Total cholesterol and LDL-cholesterol fell in both groups as did total body fat . Total body fat-free mass ( DEXA , anthropometry , impedance ) increased in the E&T group only . We concluded that in postmenopausal women , treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone . Significantly greater improvement in sexuality was observed with combined therapy , verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women . The favourable estrogenic effects on lipids were preserved in women treated with T , in association with beneficial changes in body composition 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 Young adult males who can not produce or respond to estrogen ( E ) are osteopenic , suggesting that E may regulate bone turnover in men , as well as in women . Both bioavailable E and testosterone ( T ) decrease substantially in aging men , but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss . Thus , we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men ( mean age 68 years ) , study ing them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E , withdrawing only T , or only E , or continuing both . Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones . By two-factor ANOVA , E played the major role in preventing the increase in the bone resorption markers , whereas T had no significant effect . By contrast , serum osteocalcin , a bone formation marker , decreased in the absence of both hormones , and both E and T maintained osteocalcin levels . We conclude that in aging men , E is the dominant sex steroid regulating bone resorption , whereas both E and T are important in maintaining bone formation
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 .