The long-term goal of this proposal is to determine the therapeutic efficacy of testosterone at preserving lean muscle mass, muscle strength, and bone mineral density in healthy humans during spaceflight. We propose to examine the interactive or additive effects of the combination of testosterone and exercise on lean body mass (LBM), muscle strength, and bone health. Our general hypothesis is that the maintenance of normal physiologic levels of testosterone during spaceflight will protect against the functional loss of muscle and bone, and will maximize the efficacy of existing resistance exercise protocols at preventing or reversing functional impairments that occur during bed rest.
To achieve these goals we will test the following specific hypotheses before, during, and after 70 days of bed rest:
1: Cycled testosterone replacement (weekly testosterone injections for 2 weeks, followed by 2 weeks off, etc.) in conjunction with exercise will have an additive effect in preventing loss of muscle mass and muscle strength in men representative of the astronaut population compared to exercise with placebo testosterone.
2: Cycled testosterone replacement (weekly testosterone injections for 2 weeks, followed by 2 weeks off, etc.) in conjunction with exercise will have an additive effect in preventing loss of bone mass and alterations in markers of bone metabolism in men representative of the astronaut population compared to exercise with placebo testosterone.
To address these hypotheses we will investigate the following specific aims before, during, and after 70 days of bed rest:
Aim 1: To determine the effect of cycled testosterone replacement in conjunction with resistance exercise during bed rest on muscle mass, muscle strength, and fatigue in men aged 24-55 years.
Aim 2: To determine the effect of cycled testosterone replacement in conjunction with resistance exercise during bed rest on markers of bone metabolism and bone mass in men aged 24-55 years.
Current evidence suggests that the combination of testosterone and exercise will optimize the effectiveness of the existing exercise and nutritional countermeasures. Results from this proposal will lay the ground work for the implementation of combinational countermeasures that will additively work to maintain preflight physiology of astronauts during long-term spaceflight missions.
Research Impact/Earth Benefits: Results from this study will further elucidate the role of testosterone in the maintenance of skeletal muscle and bone during long term bed rest as a model for spaceflight. The benefits to life on Earth are extensive.
It is hypothesized that maintaining appropriate balance between hormonal status, nutritional status, and physical activity during spaceflight is of critical importance in preventing musculoskeletal losses. It is our contention that the restoration of physiologic levels of testosterone is essential to prevent and/or restore spaceflight- and microgravity-induced losses in the musculoskeletal system. Current evidence suggests that the combination of testosterone and exercise will optimize the effectiveness of the existing exercise and nutritional countermeasures. |