Background: It has been suggested that the age-related decline of androgens in men plays a distinct role in the development of several aspects of frailty. Therefore, hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength, decreasing fat mass, and improving the subjective quality of life. Objective: The objective of the study was to assess whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane might improve the course of frailty. Design: This was a double-blind, randomized, controlled trial. Setting: The study was conducted in the general community. Participants: Participants included 100 nonhospitalized, nondiseased, independently living men, aged 70 yr and over with low scores on strength tests. Seventeen participants did not complete the trial. Intervention: Subjects were randomly assigned to one of four intervention arms: atamestane (100 mg/d) and placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and DHEA (50 mg/d), or two placebo tablets for 36 wk. Main Outcome Measures: Physical frailty was measured by means of a specific test battery, including isometric grip strength, leg extensor power, and physical performance. Results: The randomization was successful, and 83 (83%) men completed the intervention. There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention. Conclusions: The results of this double-blind, randomized trial do not support the hypothesis that hormone replacement with DHEA and/or atamestane might improve the course of frailty.