Sarcopenia, the aging-associated loss of muscle mass and function, is an important public health problem that contributes to frailty, decreased functional mobility, increased risk of falls and fractures, and a poor quality of life. The primary objective of the proposed competing continuation application is to determine whether testosterone replacement of older men who have low testosterone levels and are at increased risk for disability because of the presence of sarcopenia will increase their maximal voluntary muscle strength of major upper and lower extremity muscle groups. The second objective is to determine whether testosterone replacement will improve muscle power, performance in standardized, measures of physical function, reaction time, balance, and physical activity, and reduce the risk of disability. The third objective is to determine whether testosterone supplementation improves fatigue, affectivity, and overall sense of well being in older men with sarcopenia and low testosterone level. We will conduct a randomized, placebo-controlled, parallel group, double-blind trial in which 252 medically stable, older men, 65-85 years of age with total testosterone <350 ng/dL and/or free testosterone <50 pg/ml by dialysis, and sarcopenia will be randomized to receive either testosterone (10 g) or placebo gel daily for six months. Sarcopenia will be operationally defined by DEXA scanning as appendicular lean soft tissue mass that is two standard deviations below that for healthy, young men (<19.6 kg). The 10 g daily dose of testosterone gel is expected to increase serum testosterone concentrations into the mid- to high-normal range (-600-700 ng/dL). Maximal voluntary strength in the leg press, chest press, leg curls, and lastissimus pull exercises, leg power, performance in several measures of physical function (Margaria power test, walking speed, load carry, and reach and lift test), reaction time, static and dynamic balance, and self-reported disability will be assessed before, during and after 6-months of treatment. The effects of testosterone on fatigue by Chalder Fatigue Scale, affectivity by DeRogatis Affectivity Balance Scale, and sense of well being by Psychological Wellbeing Index will be assessed before, during and after treatment. For safety, we will monitor blood counts and chemistries, PSA, prostate examination, AUA/IPSS symptom score, sleep apnea, and local skin reactions. Careful subject selection, optimization of testosterone dose, the use of an objective operational definition of sarcopenia and measures of muscle performance that are important for functional activities and have been shown to be androgen-responsive, attention to effect size and power considerations, and a multi-disciplinary team of investigators will maximize the chances of finding a treatment effect, if any. The study will provide unique information about the effectiveness of a rational, but hitherto unproven therapeutic strategy, for older men with sarcopenia who are at increased risk of disability.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AG014369-10S2
Application #
8209312
Study Section
Special Emphasis Panel (ZRG1-ASG (01))
Program Officer
Romashkan, Sergei
Project Start
1997-07-01
Project End
2012-02-28
Budget Start
2011-03-15
Budget End
2012-02-28
Support Year
10
Fiscal Year
2011
Total Cost
$369,469
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Storer, Thomas W; Bhasin, Shalender; Travison, Thomas G et al. (2016) Testosterone Attenuates Age-Related Fall in Aerobic Function in Mobility Limited Older Men With Low Testosterone. J Clin Endocrinol Metab 101:2562-9
Pope Jr, Harrison G; Wood, Ruth I; Rogol, Alan et al. (2014) Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev 35:341-75
Bachman, Eric; Travison, Thomas G; Basaria, Shehzad et al. (2014) Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci 69:725-35
He, J; Bhasin, S; Binder, E F et al. (2013) Cardiometabolic risks during anabolic hormone supplementation in older men. Obesity (Silver Spring) 21:968-75
Huang, Grace; Bhasin, Shalender; Tang, Elizabeth R et al. (2013) Effect of testosterone administration on liver fat in older men with mobility limitation: results from a randomized controlled trial. J Gerontol A Biol Sci Med Sci 68:954-9
Sattler, Fred R (2013) Growth hormone in the aging male. Best Pract Res Clin Endocrinol Metab 27:541-55
Basaria, Shehzad; Davda, Maithili N; Travison, Thomas G et al. (2013) Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci 68:153-60
Guo, Wen; Bachman, Eric; Li, Michelle et al. (2013) Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells. Aging Cell 12:280-91
Schroeder, E Todd; He, Jiaxiu; Yarasheski, Kevin E et al. (2012) Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation. Eur J Appl Physiol 112:1123-31
Kumar, R; Atamna, H; Zakharov, M N et al. (2011) Role of the androgen receptor CAG repeat polymorphism in prostate cancer, and spinal and bulbar muscular atrophy. Life Sci 88:565-71

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