Testosterone Supplementation as a Countermeasure against Musculoskeletal Losses during Space Exploration

The long-term goal of this proposal was to determine the therapeutic efficacy of testosterone at preserving lean muscle mass, muscle strength, and bone mineral density in healthy humans during spaceflight. We proposed 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 tested 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 investigated 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.

Results from this study will further elucidate the role of testosterone in the maintenance of skeletal muscle and bone during long term bed rest and spaceflight. The benefits to life on Earth are extensive.

This study demonstrates that testosterone treatment in conjunction with exercise countermeasures is corrective against head down bed rest (HDBR) induced changes in body composition of healthy men. Exercise countermeasures were protective against HDBR induced declines in LBM and strength. However, the addition of low dose intermittent testosterone treatment was necessary to promote increases in LBM and protect against increases in fat mass. Furthermore, changes in leg LBM correlated directly with changes in lower body strength. Understanding the unique synergy between exercise dosing and testosterone supplementation could have important implications for both clinical outcomes and spaceflight operations.

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