The long-term goal of this project is to better understand the physiological significance of the age related decline in serum testosterone (T) levels and the role of T supplementation, with and without exercise, in attenuating the reduced physical function and frailty found in aging men. Studies suggest that T replacement in healthy elderly men has beneficial effects on body composition, muscle, bone, memory and behavior, but the risks of chronic treatment, especially on the prostate, heart and sleep quality, are not entirely clear. Therefore, it is most desirable to supplement into the lowest """"""""effective"""""""" range in elderly men. However, the effects of lower than usual replacement T doses have not been well studied. Furthermore, the possible important interaction of exercise to enhance the positive effects of T supplementation yet mitigate the possible side effects has not been studied in older men. A randomized, double-blinded, placebo-controlled study (complete, balanced, 2-way factorial design) will be performed. The factors are testosterone dose (placebo, low-dose [25 mg/d], usual-dose [50 mg/d]) crossed with progressive resistance training (some versus none). This study will determine: 1) the beneficial (body composition, physical performance, and functional performance) and adverse (erythrocytosis, and prostate growth) effects of low-dose versus usual replacement-dose T therapy (as T gel; AndroGelmM), in healthy older men with low normal to slightly low serum T levels; and 2) the possible positive interaction between low-dose T supplementation and progressive resistance training to further enhance anabolic and functional effects while reducing side effects. These studies will provide important new information regarding the risk/benefit profile of low-dose T supplementation compared to conventional T replacement doses. These studies will also influence future development of androgen formulations and guide intervention trials to assess the benefits and risks of T treatment, in both healthy and frail elderly men, to prevent frailty and help restore function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG019339-04
Application #
7218657
Study Section
Special Emphasis Panel (ZRG1-OBM-2 (03))
Program Officer
Romashkan, Sergei
Project Start
2004-05-01
Project End
2009-04-30
Budget Start
2007-05-15
Budget End
2008-04-30
Support Year
4
Fiscal Year
2007
Total Cost
$958,058
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Hildreth, Kerry L; Schwartz, Robert S; Vande Griend, Joseph et al. (2018) Effects of Testosterone and Progressive Resistance Exercise on Vascular Function in Older Men. J Appl Physiol (1985) :
Broccardo, Carolyn J; Schauer, Kevin L; Kohrt, Wendy M et al. (2013) Multiplexed analysis of steroid hormones in human serum using novel microflow tile technology and LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 934:16-21
Hildreth, Kerry L; Barry, Daniel W; Moreau, Kerrie L et al. (2013) Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab 98:1891-900
Hildreth, Kerry L; Van Pelt, Rachael E; Schwartz, Robert S (2012) Obesity, insulin resistance, and Alzheimer's disease. Obesity (Silver Spring) 20:1549-57
Ginde, A A; Wolfe, P; Camargo Jr, C A et al. (2012) Defining vitamin D status by secondary hyperparathyroidism in the U.S. population. J Endocrinol Invest 35:42-8
Kohrt, Wendy M; Barry, Daniel W; Schwartz, Robert S (2009) Muscle forces or gravity: what predominates mechanical loading on bone? Med Sci Sports Exerc 41:2050-5
Alvord, Lori Arviso; Henderson, William G; Benton, Kathryn et al. (2009) Surgical outcomes in American Indian veterans: a closer look. J Am Coll Surg 208:1085-92.e1
Ginde, Adit A; Scragg, Robert; Schwartz, Robert S et al. (2009) Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc 57:1595-603