MON-225 A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women with Anorexia Nervosa

Background: Anorexia nervosa is a serious psychiatric illness with significant mortality and no approved medical therapies. Comorbid affective disorders are highly prevalent, and we have shown that relative androgen deficiency in anorexia nervosa is associated with depression and anxiety symptom severity. As women with anorexia nervosa are relatively testosterone deficient, we hypothesized that physiologic testosterone therapy would improve weight, depressive and anxiety symptoms, and eating disorder symptoms and behavior. Methods: 90 women 18-45 yo with anorexia nervosa and free testosterone levels below the median for healthy young women were randomized to testosterone 300 mcg daily or placebo patch (Procter & Gamble) for 6 months. % free testosterone was measured by equilibrium dialysis and total testosterone by HTLC (Mayo Labs). Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV. Depression and anxiety symptom severity were assessed [Hamilton Depression Rating Scale (HAM-D); Hamilton Anxiety Rating Scale (HAM-A)]. Eating disorder psychopathology/behaviors were assessed [Eating Disorder Examination (EDE) and Eating Disorder Inventory-2 (EDI-2)]. Primary outcome was BMI. Secondary outcomes were HAM-D, HAM-A, EDE, and EDI-2 scores. Results: Baseline characteristics, including mean testosterone levels, did not differ between the active and placebo groups. Mean age was 27±7(SD) years, BMI 18.3±1.6 kg/m(2), and free testosterone 0.4±0.2 ng/dL (normal: 0.3-1.9 ng/dL). 64% of subjects met criteria for major depressive disorder and 68% for generalized anxiety disorder. Mean HAM-D score was 15±4 (moderate depression severity) and mean HAM-A score was 15±5 (mild anxiety severity). Groups did not differ in % of subjects who started/discontinued (44%) or changed psychiatric medication dose (30%) during the study. Mean increase in serum free testosterone was 0.9±0.9 ng/dL in the testosterone group. Mean BMI increased by 0.02±1.01 kg/m(2) in the active, and 0.5±1.1 kg/m(2) in the placebo, group (p=0.03) over 6 months. At 4 weeks, there was a trend toward a greater decrease in mean depression (-1.6±2.8 vs -0.7±3.0, p=0.09 by HAM-D), but not anxiety, severity score in the testosterone vs. placebo group. At 6 months, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D -2.9±4.9 (testosterone) vs -3±5 (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 EDE or EDI-2 scores between groups. Testosterone was well-tolerated with no difference between groups in androgenic side effects. Conclusion: Contrary to what was hypothesized, low-dose testosterone therapy for 6 months in women with anorexia nervosa resulted in less weight gain, and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms, relative to placebo.