Growth Hormone Replacement in Healthy Older Men Improves Body Composition but Not Functional Ability Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. Hormone therapy and physical function change among older women in the Women's Health Initiative: a randomized controlled trial The effects of five‐year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients The effect of hormone replacement therapy on appendicular lean tissue mass in early postmenopausal women A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women. Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women. Resistance training in postmenopausal women with and without hormone therapy. Long-Term Prevention with Hormone-Replacement Therapy after the Menopause: Which Women should be Targeted? HRT and cardiovascular disease.
Aging is associated with alterations in body composition and a decline in functional status . Healthy older persons have decreased muscle mass , increased fat mass , and decreased strength [ 1 - 3 ] . The muscle strength of 70-year-old men is about half that of young adults [ 3 ] . The risk for falls , fractures , and frailty increases with age-related decreases in muscle strength [ 4 - 6 ] . Pituitary secretion of growth hormone and circulating levels of insulin-like growth factor 1 decrease with aging [ 7 ] ; these events are called somatopause . Growth hormone is both anabolic and lipolytic [ 8 - 10 ] , and the action of growth hormone on peripheral tissues is mediated , in part , by circulating insulin-like growth factor 1 [ 11 ] . Growth hormone deficiency results in body composition changes that are similar to the changes seen with aging [ 1 , 7 ] . Growth hormone replacement in patients with hypopituitarism and in older men reverses some of the body composition changes associated with both growth hormone deficiency and aging [ 12 - 14 ] . In a study by Rudman and colleagues [ 14 ] on the effects of growth hormone replacement therapy on body composition , the administration of growth hormone to 12 men 61 to 73 years of age for 6 months increased lean body mass by 9 % and decreased adipose tissue mass by 15 % ( P < 0.005 ) . Circulating insulin-like growth factor 1 levels increase similarly in young and old men after exogenous administration of either growth hormone or growth hormone-releasing hormone [ 7 , 11 ] . Therefore , low insulin-like growth factor 1 levels reflect decreased growth hormone secretion rather than a loss of hepatic responsiveness to the hormone . On the basis of these data , it has been proposed that diminished secretion of growth hormone is responsible , in part , for the somatic changes of aging [ 14 ] . Growth hormone replacement has been shown to improve muscle volume , isometric strength , and exercise capacity in young adults with hypopituitarism [ 12 , 13 ] . In one study of growth hormone-deficient young adults treated with growth hormone [ 12 ] , thigh muscle volume increased by 6 % ( P < 0.01 ) , and isometric strength increased by 8 % ( P = 0.08 ) compared with controls . Increases in isometric strength were associated with increases in muscle volume ( r = 0.75 ; P < 0.001 ) . Exercise capacity also increased by 12 % ( P < 0.05 ) . Such data on the effects of growth hormone replacement therapy on strength or function are not available for older persons . To test the hypothesis that the muscle weakness and functional decline associated with aging are in part due to decreased growth hormone secretion , we conducted a 6-month r and omized , controlled , double-blind trial comparing recombinant human growth hormone therapy with placebo in 56 elderly men whose baseline insulin-like growth factor 1 levels were less than the tenth percentile found in younger healthy adults . Methods Participants We recruited healthy , ambulatory , community-dwelling men older than 69 years of age . Because growth hormone secretion is pulsatile and diurnal , a more convenient measure of growth hormone secretion is insulin-like growth factor 1 , which has constant and nonpulsatile plasma levels [ 1 , 7 , 15 , 16 ] . Inclusion criteria included two fasting morning plasma insulin-like growth factor 1 levels ( assayed after plasma was extracted with acid ethanol by the Nichols Institute [ 17 ] ) less than 161 ng/mL that were obtained at least 2 weeks apart , a fasting blood glucose level less than 8.4 mmol/L ( 140 mg/dL ) , stable body weight between 80 % and 120 % of ideal body weight [ 18 ] during the previous year , and a normal complete blood count at baseline . Participants had to be able to follow the study instructions and perform the strength measurements . Exclusion criteria included diseases that might contraindicate the use of growth hormone ( such as carcinoma within the previous 5 years , diabetes mellitus , and the carpal tunnel syndrome ) , uncontrolled hypertension ( blood pressure more than 180/100 mm Hg ) , oral corticosteroid use within the previous year , or a recent change in ambulatory status ( for example , as the result of a stroke ) . Design After the participants gave informed written consent , the following baseline measurements were obtained : question naires ( demographic characteristics and medical conditions ) ; fasting blood chemistry ( levels of electrolytes , urea nitrogen , creatinine , glucose , calcium , phosphate , and albumin ) ; complete blood count ; serum and rogen levels ( total and free testosterone and dehydroepi and rosterone ) ; fasting lipoprotein levels ( total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and triglycerides ) and thyroid-stimulating hormone and free thyroxine levels ; 24-hour urinary calcium excretion ; and creatinine clearance . At baseline , we also measured the body composition , strength , and functional ability of all participants . We then used a computer-generated r and omization table to assign each participant to receive either growth hormone or placebo . Participants , investigators who had contact with the participants , and laboratory personnel were blinded to treatment status . Treatment consisted of recombinant human growth hormone ( somatropin [ Nutropin , Genentech ] ) , 0.03 mg/kg of body weight , or an equivalent placebo volume ( supplied in identical vials by Genentech ) injected subcutaneously three times per week in the morning for 6 months . We evaluated the participants after 2 , 4 , 8 , 12 , 18 , and 24 weeks of treatment to determine whether side effects developed and to ensure compliance . Participants were examined and specifically asked about the presence of the following side effects : malaise , fatigue , edema , arthralgias , arthritis , the carpal tunnel syndrome , muscle discomfort , dyspnea , depression , polydipsia , polyuria , nocturia , and tender or enlarged breasts . At each visit , we measured fasting morning plasma insulin-like growth factor 1 levels 48 hours after the last treatment dose and repeated most of the baseline blood and urinary tests . We adjusted the dose of recombinant human growth hormone to maintain serum insulin-like growth factor 1 levels between 190 and 350 ng/mL ( the 25th to 75th percentiles of a young adult population ) 48 hours after a dose . To preserve blinding , each growth hormone recipient was paired with a placebo recipient . An unblinded physician who had not had contact with the participants review ed insulin-like growth factor 1 levels during the trial . If the levels were less than 190 ng/mL or greater than 350 ng/mL , the unblinded physician instructed study personnel to make identical dose adjustments for both participants in the pair . The dose was also decreased in any participant who reported troublesome side effects that were potentially attributable to growth hormone . We repeated all study outcome measurements after 6 months of treatment . We also measured fasting plasma renin activity , cortisol and aldosterone levels , and 24-hour urine aldosterone excretion . The investigational review boards of the University of California , San Francisco , and the Department of Veterans Affairs Medical Center , San Francisco , approved the study protocol . Measurements Body Composition We used dual-energy x-ray absorptiometry ( Lunar DPX-Plus , Madison , Wisconsin ) total-body composition scans to measure lean tissue mass and fat mass , and we used anterior-posterior lumbar scans to measure bone mineral content . We measured skin thickness using ultrasonography with a 10-MHz transducer ( Diasonics , Milpitas , California ) that was positioned transversely 5 cm below the umbilicus . Using the same transducer , we made two ultrasonographic measurements on each participant . The average of the two measurements was used for analysis . The study radiologist , who was blinded to the participants ' treatment status , interpreted all test results . Muscle Strength The study 's physical therapist measured the muscle strength of the participants ' knee flexor and extensor muscles using an isokinetic dynamometer ( Cybex 340 , Lumex , Bay Shore , New York ) . Using a st and ard protocol , we measured peak torque of knee flexion and extension at joint speeds of 90 , 120 , and 180 degrees per second . We measured h and grip strength according to a st and ardized protocol using a grip dynamometer ( Smedley Grip Dynamometer , JA Preston , Jackson , Mississippi ) . The greater of the two measurements was used for analysis . Systemic Endurance To assess systemic endurance , we measured maximal oxygen consumption ( Vo 2 max ) during exercise cycle testing . Upright exercise testing was done using an electronically braked cycle ergometer ( Erich Jaeger , Rockford , Illinois ) . Exercise was initially done unloaded and was then increased by 25 watts every 2 minutes . Participants continued to exercise until they were exhausted or unable to maintain critical pedal frequency ( greater than 50 revolutions per minute ) . During exercise cycle testing , we continuously measured respiratory gas exchange to determine Vo 2 max ( Ergopneumotest , Erich Jaeger ) . Physical Performance The study 's physical therapist used the Physical Performance Test [ 19 ] to assess the participants ' performance on nine physical functions . Participants were asked to write a prescribed sentence , transfer kidney beans using a teaspoon , place a heavy book on a shelf , remove a jacket , pick up a penny from the floor , turn 360 degrees , walk a 50-foot walking test course , and climb stairs to determine speed and the number of flights climbed before the development of fatigue . The test score is based on the time required to complete each task . Higher scores ( the best performance is a maximum score of 36 ) are associated with the shortest time required to complete a task and with better functional status . Cognitive Function and Mood Each participant completed the Trails B Test , the Mini-Mental State Examination , the Digit Symbol Substitution Test , and the Geriatric Depression Scale [ 20 - 23 ] . The Trails B Test ( from the Halstead-Reitan Neuropsychological Test The aim of this study was to study the influence of hormone replacement therapy ( HRT ) on weight changes , body composition , and bone mass in early postmenopausal women in a partly r and omized comprehensive cohort study design . A total of 2016 women ages 45 - 58 years from 3 months to 2 years past last menstrual bleeding were included . One thous and were r and omly assigned to HRT or no HRT in an open trial , whereas the others were allocated according to their preferences . All were followed for 5 years for body weight , bone mass , and body composition measurements . Body weight increased less over the 5 years in women r and omized to HRT ( 1.94 + /- 4.86 kg ) than in women r and omized to no HRT ( 2.57 + /- 4.63 , p = 0.046 ) . A similar pattern was seen in the group receiving HRT or not by their own choice . The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat . The main determinant of the weight gain was a decline in physical fitness . Women opting for HRT had a significantly lower body weight at inclusion than the other participants , but the results in the self-selected part of the study followed the pattern found in the r and omized part . The change in fat mass was the strongest predictor of bone changes in untreated women , whereas the change in lean body mass was the strongest predictor when HRT was given . Body weight increases after the menopause . The gain in weight is related to a decrease in working capacity . HRT is associated with a smaller increase in fat mass after menopause . Fat gain protects against bone loss in untreated women but not in HRT-treated women . The data suggest that women 's attitudes to HRT are more positive if they have low body weight , but there is no evidence that the conclusions in this study are skewed by selection bias Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population Objective : Few studies have investigated the relationships between body composition , functional ability , and age-related disability in postmenopausal women . We investigated the relative role of fat mass , lean mass , and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years . Design : We performed a cross-sectional study among 396 independently living women aged 56 - 73 years , r and omly selected between 8 and 30 years after menopause .  Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry . Muscle strength ( grip and leg extensors ) was assessed using dynamometry . Functional ability was estimated by Physical Performance Score , physical activity during the preceding year , and impairment in activities of daily living . Results : Of the participants , 43.7 % were overweight ( 25 ≥ BMI < 30 kg/m2 ) , and 17.7 % were obese ( BM I ≥ 30 kg/m2 ) . Higher muscle strength was observed with increasing lean body mass , and participants with higher muscle strength scored better in the physical performance score and activities of daily living . Higher fat mass was significantly associated with a lower physical performance score , lower physical activity , and a higher frequency of disability . Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio . The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs . Conclusions : Our results support the role of fat mass as the primary risk marker for disability , which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years OBJECTIVE Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes , possibly related to reduced output of ovarian steroids . In this study we examined the effect of combined postmenopausal hormone replacement therapy ( HRT ) on the total and regional distribution of fat and lean body mass . RESEARCH METHODS AND PROCEDURES Sixteen healthy postmenopausal women ( age : 55 + /- 3 years ) were studied in a placebo-controlled , crossover study and were r and omized to 17beta estradiol plus cyclic norethisterone acetate ( HRT ) or placebo in two 12-week periods separated by a 3-month washout . Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods . Changes were compared by a paired Student 's t test . RESULTS The change in body weight during HRT was equal to the change during placebo ( -24.6 g vs. -164 g , p = 0.42 ) , but relative fat mass was significantly reduced ( -0.5 % vs. + 1.24 % , p < 0.01 ) . During HRT , compared with during placebo , lean body mass increased ( + 347 g vs. -996 g , p < 0.01 ) and total fat mass decreased ( -400 g vs. + 836 g , p = 0.06 ) . Total bone mineral content increased ( + 28.9 g vs. -4.4 g , p = 0.04 ) and abdominal fat decreased ( -185 g vs. + 253 g , p = 0.04 ) during HRT compared with placebo . DISCUSSION HRT is linked to the reversal of both menopause-related obesity and loss of lean mass , without overall change in body weight . The increase in lean body mass during HRT is likely explained by muscle anabolism , which in turn , prevents disease in the elderly Patients with chronic obstructive pulmonary disease ( COPD ) often develop weight loss , which is associated with increased mortality . Recombinant human growth hormone ( rhGH ) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients . The aim of this study was to assess the effects of rhGH administration on the nutritional status , resting metabolism , muscle strength , exercise tolerance , dyspnea , and subjective well-being of underweight patients with stable COPD . Sixteen patients attending a pulmonary rehabilitation program ( age : 66 + /- 9 yr ; weight : 77 + /- 7 % of ideal body weight ; FEV1 : 39 + /- 13 % of predicted ) were r and omly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion . Measurements were made at the beginning ( DO ) and at the end ( D21 ) of treatment and 2 mo later ( D81 ) . Body weight was similar in the two groups during the study , but lean body mass was significantly higher in the rhGH group at D21 ( p < 0.01 ) and D81 ( p < 0.05 ) . The increase in lean body mass was 2.3 + /- 1.6 kg in the rhGH group and 1.1 + /- 0.9 kg in the control group at D21 and 1.9 + /- 1.6 kg in the rhGH group and 0.7 + /- 2.1 kg in the control group at D81 . At D21 , the resting energy expenditure was increased in the rhGH group ( 107.8 % of DO , p < 0.001 compared with the control group ) . At D21 and D81 , the changes in maximal respiratory pressures , h and grip strength , maximal exercise capacity , and subjective well-being were similar in the two groups . At D21 , the 6-min walking distance decreased in the rhGH group ( -13 + /- 31 % ) and increased in the control group ( + 10 + /- 14 % ; p < 0.01 ) . We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD 1 . A r and omized controlled trial of the effect of oral hormone replacement therapy plus calcium compared with calcium alone on balance , muscle performance and falls was conducted over 48 weeks in 116 post-menopausal women ( aged 45 - 70 years ) , all of whom had suffered a distal radial fracture during the previous 3 months . Treatment was with Prempak C or Premarin 0.625 mg in the test group with 1 g calcium daily ( S and ocal ) in both groups . Measurements were made of balance , assessed as sway , leg extensor power and self-paced walking speed , at 12-week intervals over 24 weeks . H and grip strength was measured every 12 weeks for 48 weeks , and falls in the preceding 12 weeks were recorded at each visit . 2 . There was no relation between initial levels of oestradiol and any other variable assessed , except body mass . Levels of follicle-stimulating hormone in the test group were in the premenopausal range . There was no significant change attributable to hormone replacement therapy at any time point in any of the outcome variables . The only significant difference was an increase of 4.2 % ( 95 % confidence interval 0.7 - 7.6 % ) in leg extensor power in the control group ( calcium alone ) compared with the group treated with hormone replacement therapy . 3 . Of the total group , 37 % fell again during the year , with three patients suffering a further fracture . Frequent fallers swayed significantly more often than the others , but there was no evidence that their muscle strength was poorer or that the group treated with hormone replacement therapy fell less frequently . 4 . Hormone replacement therapy did not increase muscle performance , improve balance or reduce falls over a year in middle-aged women BACKGROUND Apparently discrepant findings have been reported by the Women 's Health Initiative ( WHI ) trial compared with observational studies of postmenopausal hormone therapy ( HT ) and coronary heart disease ( CHD ) . METHODS We prospect ively examined the relation of HT to CHD , according to timing of hormone initiation relative to age and time since menopause . Participants were postmenopausal women in the Nurses ' Health Study , with follow-up from 1976 to 2000 . Information on hormone use was ascertained in biennial , mailed question naires . We used proportional hazards models to calculate multivariable adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) . We also conducted sensitivity analyses to determine the possible influence of incomplete capture of coronary events occurring shortly after initiation of HT . RESULTS Women beginning HT near menopause had a significantly reduced risk of CHD ( RR = 0.66 , 95 % CI 0.54 - 0.80 for estrogen alone ; RR = 0.72 , 95 % CI 0.56 - 0.92 for estrogen with progestin ) . In the subgroup of women demographically similar to those in the WHI , we found no significant relation between HT and CHD among women who initiated therapy at least 10 years after menopause ( RR = 0.87 , 95 % CI 0.69 - 1.10 for estrogen alone ; RR = 0.90 , 95 % CI 0.62 - 1.29 for estrogen with progestin ) . Among women who began taking hormones at older ages , we also found no relation between current use of estrogen alone and CHD ( for women aged 60 + years , RR = 1.07 , 95 % CI 0.65 - 1.78 ) , although there was a suggestion of possible reduced risk for combined HT ( RR = 0.65 , 95 % CI 0.31 - 1.38 ) . In sensitivity analyses , we found that the incomplete capture of coronary events occurring shortly after initiation of HT could not explain our observation of a reduced risk of coronary disease for current users of HT . CONCLUSIONS These data support the possibility that timing of HT initiation in relation to menopause onset or to age might influence coronary risk Objective : Although estrogen may be linked to biological pathways that maintain higher physical function , the evidence is derived mostly from observational epidemiology and therefore has numerous limitations . We examined whether hormone therapy affected physical function in women 65 to 79 years of age at enrollment . Methods : This study involves an analysis of the Women 's Health Initiative r and omized controlled trials of hormone therapy in which 922 nondisabled women who had previous hysterectomies were r and omized to receive estrogen therapy or a placebo and 1,458 nondisabled women with intact uteri were r and omized to receive estrogen + progestin therapy or a placebo . Changes in physical function were analyzed for treatment effect , and subgroup differences were evaluated . All women completed performance-based measures of physical function ( grip strength , chair st and s , and timed walk ) at baseline . These measures were repeated after 1 , 3 , and 6 years . Results : Overall , participants ' grip strength declined by 12.0 % , chair st and s declined by 3.5 % , and walk pace slowed by 11.4 % in the 6 years of follow-up ( all P values < 0.0001 ) . Hormone therapy , as compared with placebo , was not associated with an increased or decreased risk of decline in physical function in either the intention-to-treat analyses or in analyses restricted to participants who were compliant in taking study pills . Conclusions : Hormone therapy provided no overall protection against functional decline in nondisabled postmenopausal women 65 years or older in 6 years of follow-up . This study did not address the influence of hormone therapy for women of younger ages Objective Little is known of the long‐term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency ( GHD ) . In this study , the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD Objective The impact of hormone replacement therapy ( HRT ) on skeletal muscle mass is still a controversial issue in women 's health . Some authors hypothesize anabolic effects , others catabolic . These hypotheses , however , await confirmation by longitudinal observations based on more direct measurements of muscle mass . The aim of the present preliminary study was to evaluate the effect of a 3-year HRT program on appendicular lean tissue mass ( LTMA ) in early postmenopausal women aged 45–54 years . Design This was a r and omized , double-blind and placebo-controlled trial . Women received HRT with 2 mg estradiol valerate combined either continuously with 1 mg cyproterone acetate ( days 1–28;n = 15 ) or sequentially with 75 & mgr;g levonorgestrel ( days 17–28;n = 15 ) , or placebo ( n = 18 ) . Serum estradiol was measured by radioimmunoassay . LTMA was measured by dual photon absorptiometry ( baseline ) and dual energy X-ray absorptiometry ( years 2 and 3 ) . Results Baseline serum estradiol did not show significant correlation with the respective LTMA ( r = 0.018 , p = 0.88 , n = 75 ) . Cross-sectional analysis found no significant differences between the intervention groups at any time points . The longitudinal changes between years 2 and 3 showed a trend toward decreasing LTMA in those receiving HRT ( −0.08 ± 0.12 kg , n = 30 ) compared to those receiving placebo ( 0.12 ± 0.25 kg , n = 18 , p = 0.44 ) . Conclusions The present preliminary study did not find significant effects on LTMA caused by HRT . The trends toward decreasing LTMA in the HRT groups might suggest catabolic rather than anabolic effects . These trends , however , await confirmation by larger clinical trials Background Sarcopenia , the age-related loss of muscle mass [ defined as appendicular LBM/Height2 ( aLBM/ht2 ) below peak value by>1SD ] , strength and function , is a major contributing factor to frailty in the elderly .  MK-0773 is a selective and rogen receptor modulator design ed to improve muscle function while minimizing effects on other tissues . Objectives The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass ( LBM ) in sarcopenic frail elderly women treated with MK-0773 relative to placebo . Design This was a r and omized , double-blind , parallel-arm , placebo-controlled , multicenter , 6-month study . Participants were r and omized in a 1:1 ratio to receive either MK-0773 50 mg b.i.d . or placebo ; all participants received Vitamin D and protein supplementation . Setting General community . Participants 170 Women aged ≥65 with sarcopenia and moderate physical dysfunction . Measurements Dual energy X-ray absorptiometry , muscle strength and power , physical performance measures . Results Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo ( p<0.001 ) . Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6 , but the mean difference between the two groups was not significant ( p=0.269 ) . Both groups showed significant improvement from baseline at Month 6 in physical performance measures , but there were no statistically significant differences between participants receiving MK-0773 and placebo . A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo , which resolved after discontinuation of study therapy . MK-0773 was generally well-tolerated with no evidence of and rogenization . Conclusions The MK-0773-induced  increase in LBM did not translate to improvement in strength or function vs. placebo . The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation BACKGROUND Menopause is associated with decreases in lean mass and increases in fat mass . Serum hormone levels and hormone replacement therapy ( HRT ) may modify the effects of exercise training on body composition in postmenopausal women . METHODS We assessed the changes in total body and regional lean soft tissue and fat mass ( using dual-energy x-ray absorptiometry ) in 94 sedentary postmenopausal women , aged 40 - 65 years , after 12 months of resistance and weight-bearing aerobic exercise training . Women currently on oral HRT ( n = 39 ) and not on HRT ( n = 55 ) were r and omized within groups to exercise and no exercise , result ing in four groups : exercise + HRT ( n = 20 ) , HRT ( n = 22 ) , exercise ( n = 24 ) , and control ( n = 28 ) . Fasting blood sample s were measured for resting serum total levels of estrone , estradiol , cortisol , and rostenedione , growth hormone , and insulin-like growth factor 1 at baseline and 12 months . RESULTS We found significant effects of exercise on increases in total body , arm , and leg lean soft tissue mass , and decreases in leg fat mass and percentage of body fat . There were no interaction effects of exercise and HRT on the changes in muscle strength and body composition . No significant changes in total hormone levels were found after 12 months . CONCLUSIONS Exercise training result ed in significant beneficial changes in lean soft tissue and fat mass in early postmenopausal women . These changes in body composition were neither influenced by prolonged HRT use nor accompanied by changes in total levels of the hormones determined in this study OBJECTIVES To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women . DESIGN Double-blind , placebo-controlled trial . SETTING Clinical research center in Connecticut . PARTICIPANTS Healthy , community-dwelling women aged 65 and older ( n=167 ) . INTERVENTION Eligible women were r and omly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months . All women ( estradiol or placebo ) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months . All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day . MEASUREMENTS Appendicular skeletal muscle mass ( ASM ) , lean body mass ( LBM ) , and percentage body fat were measured using dual x-ray absorptiometry . Sarcopenia was defined as skeletal muscle mass ( ASM/height2 ) 2 st and ard deviations or less than young , healthy reference population mean . Physical activity ( Physical Activity Scale in the Elderly ( PASE ) ) and performance were measured . Serum estrone , estradiol , and sex hormone-binding globulin were measured . RESULTS The prevalence of sarcopenia at baseline was 13 % . There were no baseline differences between groups except for PASE score and chair rise time , in which the estrogen group had better performance . No changes in ASM , LBM , percentage of body fat , or physical performance were found after 3 years of estrogen therapy . CONCLUSION Sarcopenia was present in 13 % of this group of community-dwelling , postmenopausal older women . Ultra-low-dose estrogen therapy neither improves nor harms ASM . Similarly , no changes in body fat or physical performance were detected PURPOSE The main purpose of this study was to analyze the impact of a 1-yr resistance-training program on body composition and muscle strength in postmenopausal women , and to describe the impact of hormone replacement therapy ( HRT ) on body composition changes , with and without exercise . Secondarily , we wanted to study dose-response relationships between measures of program compliance and changes in primary outcomes . METHODS Subjects were postmenopausal women ( 40 - 66 yr ) r and omly assigned to an exercise ( EX ) group ( N = 117 ) and a nonexercise group ( N = 116 ) . The EX group participated in a 1 yr trainer-supervised resistance-training program , 60 - 75 min.d-1 , 3 d.wk-1 . Lean soft tissue ( LST ) and fat tissue ( FT ) changes were measured by dual-energy x-ray absorptiometry and strength by one-repetition maximum testing . RESULTS Significant ( P < 0.001 ) gains in LST were observed for women who exercised , regardless of HRT status , whereas women who did not exercise lost LST ( P < 0.05 ) if they were not taking HRT , and gained LST ( P = 0.08 ) if they were on HRT . The only significant FT losses were observed for women who exercised while on HRT ( P < 0.05 ) . Strength increases were observed at all sites ( P < 0.001 ) . Total weight lifted by subjects in their training sessions was a significant predictor of changes in LST ( P < 0.001 ) and strength ( P < 0.01 ) . CONCLUSIONS Resistance and weight-bearing exercise significantly changed total and regional body composition in postmenopausal women by increasing LST in all women and decreasing FT in women on HRT . Hormone therapy showed no independent effects on body composition , but it protected nonexercising women from losses in LST . The lean and muscle strength changes observed were partially dependent on the volume of training , as expressed by attendance and total weight lifted in 1 yr of training For decades , hormone-replacement therapy ( HRT ) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency . Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherogenesis and coronary heart disease ( CHD ) in women after the menopause . However , the fact that these promising results were not translated into lower incidences of CHD events in hormone-treated women compared with placebo in subsequent , large , r and omized studies of healthy subjects as well as women with known CHD raised a very intense debate concerning the safety of HRT in terms of cardiovascular risk . A critical mass of data points toward a protective influence of HRT on cardiovascular disease end points in early postmenopausal women , but increased harm in elderly women , especially those with abdominal adiposity or metabolic syndrome . Once the quasi-hysterical reaction to the largest of the r and omized studies ( the Women 's Health Initiative ) has abated , a future strategy should be to concentrate on identifying those relatively few individuals who are not suitable for HRT , as HRT still remains the most thoroughly investigated pharmacological prevention strategy of osteoporosis Hormone replacement therapy ( HRT ) has profound effects on the cardiovascular system , with plausible biological mechanisms explaining both the benefits and harm . Benefits may result from oestrogen action on metabolic risk factors , such as lipids , glucose and insulin metabolism , as well as direct arterial effects , reducing atherogenesis . Harm may arise from inappropriately high starting doses causing transient increases in coagulation activation and adverse vascular remodelling . Observational studies of HRT suggest that there is a beneficial effect on the incidence of coronary heart disease ( CHD ) . Any benefit of HRT seen in r and omized clinical trials appears to be confined to those women within several years of their menopause , and it is clear from the r and omized trials that age at initiation is a crucially important consideration . Women initiating HRT within 10 years of menopause onset may achieve cardiovascular benefit , particularly in terms of primary CHD prevention , whilst avoiding risks of stroke and venous thrombo-embolism
Conclusions and Relevance This systematic review and meta- analysis did not show a significant beneficial or detrimental association of HT with muscle mass .
Importance Hormone therapy ( HT ) has been suggested for protection against age-related muscle weakness in women .
However , the potential for HT-associated health risks necessitates a better underst and ing of the direction and magnitude of the association between HT and health outcomes , such as lean body mass ( LBM ) .
Objective To determine whether HT was associated with reduced LBM loss compared with not receiving HT  among postmenopausal women aged 50 years and older .