Abstract Context Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity. Objective To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN. Design Double-blind, randomized, placebo-controlled trial. Setting Clinical research center. Participants Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women. Intervention Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks. Main Outcome Measures Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors. Results Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: −2.9 ± 4.9 (testosterone) vs −3.0 ± 5.0 (placebo), P = 0.72; HAM-A: −4.5 ± 5.3 (testosterone) vs −4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo. Conclusion Low-dose testosterone therapy for 24 weeks was associated with less weight gain—and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms—compared with placebo in women with AN.