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. Lowering testosterone in men to pre-pubertal levels causes adverse effects on many body functions. Specifically, men with very low testosterone levels experience bone loss, decreased muscle strength, decreased muscle size, increased fat mass, lower sexual drive, and generally feel less well than normal men. As men age, testosterone levels decline gradually (though they rarely become extremely low) and men often experience changes in testosterone-related functions. Still, the degree to which the natural reduction of testosterone may be responsible for these adverse effects is unknown. The goal of this study is to determine the level of testosterone at which these changes begins to occur and the effect of estrogen withdrawal on these dose-response relationships. This study will enroll 200 healthy men ages 20-50. Subjects will be given an injection every 4 weeks that reversible lowers their testosterone to pre-pubertal levels. (Note that when the injections are stopped, testosterone levels return promptly to normal). Each subject is also given a controlled amount of replacement testosterone gel. There are 5 possible doses of replacement testosterone (placebo, 1.25, 2.5, 5, and 10 gm/day) that are designed to produce blood testosterone levels that range from very low to normal. The dose given to each patient is randomly determined. All men also receive an aromatase inhibitor (anastrazole 1 mg po daily) to lower estrogen levels. Over the course of 16 weeks a number of measures will be tracked including bone breakdown, muscle size and strength, fat mass, sexual drive, energy levels, and mood levels. By comparing these dose-response relationships with those from SPID 0665 we will be able to assess the role that estrogen plays in key physiologic functions in men.