This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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; AndroGelTM), 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.
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