Testosterone Supplementation for Aging-Associated Sarcopenia (original) (raw)
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Testosterone Supplementation Therapy for Older Men: Potential Benefits and Risks
Journal of the American Geriatrics Society, 2000
Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded.
Does testosterone supplementation improve health and function in elderly men?
Nature Clinical Practice Endocrinology & Metabolism, 2008
BACKGROUND-Low serum testosterone levels are associated with age-related changes in physical and cognitive function. Replacement therapy could, therefore, help alleviate symptoms of aging. OBJECTIVE-To determine whether 6 months' supplementation with testosterone improved signs of aging in a population of elderly men with low-normal testosterone levels. DESIGN AND INTERVENTION-This was a double-blind, randomized, placebo-controlled trial of testosterone supplementation conducted at a single center in the Netherlands between January 2004 and April 2005. Participants were recruited by direct mailing. Inclusion criteria included age 60-80 years and a serum testosterone level below the 50 th percentile of the study population-based testosterone distribution (cutoff 13.7 nmol/l). Exclusion criteria included myocardial infarction, heart failure, malignancy, serious liver or renal disease, epilepsy, diabetes mellitus, elevated prostatespecific antigen, use of corticosteroids, and use of testosterone esters within the previous 60 days. Eligible participants were randomly allocated to receive either 80 mg oral testosterone undecenoate or placebo twice daily for 6 months. Functional ability was measured with the timed 'get up and go' test, the Stanford Health Assessment Questionnaire, an isometric handgrip strength test, and a maximal voluntary isometric leg strength test. Cognitive parameters assessed included verbal episodic memory, cognitive and perceptual speed, attention and mental flexibility, extrapersonal spatial perception, and visuospatial performance. BMD and total body composition were measured by dual-energy X-ray absorptiometry. Quality of life was assessed with the Short-Form 36 Health Survey (SF-36) and the Questions on Life Satisfaction Modules questionnaires. OUTCOME MEASURES-The main outcome measures were functional mobility, cognitive function, BMD, anthropometry, body composition, biochemical measures, quality of life, and safety parameters. RESULTS-The study enrolled 113 men in the testosterone group (mean age 67.1 years; mean serum testosterone level 11.0 nmol/l) and 110 men in the placebo group (mean age 67.4 years; mean serum testosterone level 10.4 nmol/l). Treatment adherence was >90% for both groups. When compared with the placebo group, treatment with testosterone was associated with increased lean body mass, decreased body fat mass and decreased body fat percentage (P <0.001 for all comparisons); however, no significant changes in parameters of functional ability were observed in either group. Total cholesterol and HDL cholesterol decreased in the testosterone group, whereas insulin and glucose concentrations and measures of insulin resistance increased in the placebo group.
International Journal of Impotence Research, 2008
Our intention was to examine if subnormal testosterone levels in older men were associated with a reduction in quality of life and physical and mental health, and secondly to examine if testosterone treatment could improve these conditions. We performed a nested case-control study and a 1-year testosterone intervention study. Men with subnormal testosterone had significantly higher weight, fat mass and abdominal adipose tissue. They also had significantly higher glucose and insulin levels, and they had higher triglyceride levels. Testosterone treatment had a large impact on body composition with reduced fat mass and abdominal adipose tissue and increased fat-free mass, but it did not affect weight and glucose and lipid metabolism. Bone mineral density in the hip was significantly higher after the testosterone treatment. Older men with subnormal testosterone levels had an unfavorable metabolic profile. Testosterone treatment improved body composition, but it did not reverse the unfavorable metabolic profile.
The Journal of Clinical Endocrinology & Metabolism, 2016
Context: Findings of studies of testosterone's effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied. Objective: To determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability, and physical function. Design, Setting, and Participants: This was a double-blind, placebo-controlled, randomized trial of healthy men $60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels ,50 pg/mL. Interventions: Random assignment to 7.5 g of 1% testosterone or placebo gel daily for 3 years. Outcome Measures: Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months. Results: The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean estimated between-group difference, 10.7 W [95% confidence interval (CI), 24.0 to 25.5], P = 0.026; and 22.4 W [95% CI, 4.6 to 40.3], P = 0.027), respectively. Changes in chest-press strength (estimated mean difference, 16.3 N; 95% CI, 5.5 to 27.1; P , 0.001) and power (mean difference 22.5 W; 95% CI, 7.5 to 37.5; P , 0.001), and leg-press power were significantly greater in men randomized to testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group. Conclusion: Compared with placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass, and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied.
Experimental Gerontology, 2020
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2001
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 Ϯ 4 years, range 65-87) with bioavailable testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were randomized 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 Ϯ 1.2 nmol/l (SD) to 5.6 Ϯ 3.5 nmol/l (p Ͻ .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 Ϯ 26 pmol/l to 117 Ϯ 33 pmol/l; p Ͻ .017). The testosterone group had a 0.3% gain in femoral neck BMD, whereas the control group lost 1.6% over 12 months (p ϭ .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 ϭ .017) in the testosterone group and 27% in the control group (p ϭ .06), with no statistical difference between the groups. In the testosterone group, body fat decreased from 26.3 Ϯ 5.8% to 24.6 Ϯ 6.5% (p ϭ .001), and lean body mass increased from 56.2 Ϯ 5.3 kg to 57.2 Ϯ 5.1 kg (p ϭ .001), whereas body mass did not change. Men receiving testosterone had an increase in PSA from 2.0 Ϯ 1.4 g/l to 2.6 Ϯ 1.8 g/l (p ϭ .04), whereas men receiving placebo had an increase in PSA from 1.9 Ϯ 1.0 g/l to 2.2 Ϯ 1.5 g/l (p ϭ .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 resulted in no change in signs or symptoms of prostate hyperplasia.
The Journal of Clinical Endocrinology & Metabolism, 2008
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 androgen 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 randomized 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 ϭ 0.01), and LH decreased by 50% (P Ͻ 0.001). Relative to placebo, total body FFM (P ϭ 0.03) and skeletal muscle (P ϭ 0.008) were increased and thigh skeletal muscle loss was prevented (P ϭ 0.045) with testosterone therapy and visceral fat accumulation decreased (P ϭ 0.001) without change in total body or abdominal sc FM; change in visceral fat was correlated with change in TT levels (r 2 ϭ 0.36; P ϭ 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.