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Androgen Deficiency: Association With Increased Anxiety and Depression Symptom Severity in Anorexia Nervosa

Karen K. Miller, M.D.; Tamara L. Wexler, M.D., Ph.D.; Alicia M. Zha, B.S.; Elizabeth A. Lawson, M.D.; Erinne M. Meenaghan, N.P.; Madhusmita Misra, M.D.; Anna B. Binstock, B.A.; David B. Herzog, M.D.; and Anne Klibanski, M.D.

Objective: Anorexia nervosa is associated with a high prevalence of psychiatric comorbidities, including anxiety and depression, and with endocrine dysfunction, including relative androgen deficiency compared with healthy young women. Because androgens are known to affect mood and behavior, we hypothesized that low endogenous androgen production in anorexia nervosa would predict anxiety and depression severity.

Method: Serum androgen levels and severity of depression (Hamilton Rating Scale for Depression) and anxiety (Hamilton Rating Scale for Anxiety) were measured in 43 community-dwelling women with DSM-IV-defined anorexia nervosa from May 2004 to July 2006.

Results: Strong inverse associations were observed between both total and free testosterone and anxiety and depression severity, independent of weight. Free testosterone was also inversely associated with 4 eating-disordered thinking and behavior subscales of the Eating Disorder Inventory 2 (EDI-2). Mean free testosterone blood levels were lower in women with clinically significant anxiety and in women with clinically significant depression, compared with those without. In stepwise regression models, free testosterone was an important predictor of anxiety and depression severity. EDI-2 ineffectiveness, perfectionism, interpersonal distress, and social insecurity scores were also inversely associated with androgen levels, independent of weight.

Conclusions: Our data suggest that low androgen levels may contribute to anxiety, depression, and eating-disordered thinking and behavior in women with anorexia nervosa and form the basis for future studies to investigate the effectiveness of androgen replacement therapy.

Clinical Trials Registration: identifier NCT00089843.

(J Clin Psychiatry 2007;68:959-965)

Received Dec. 8, 2006; accepted March 22, 2007. From the Neuroendocrine Unit (Drs. Miller, Wexler, Lawson, Misra, and Klibanski and Mss. Zha, Meenaghan, and Binstock) and the Harris Center and Department of Psychiatry (Dr. Herzog), Massachusetts General Hospital and Harvard Medical School, Boston.

This work was supported in part by the following National Institutes of Health grants: NIH-R01-DK52625 and MO1 RR01066.

The authors thank the nurses and bionutritionists of the Massachusetts General Hospital General Clinical Research Center and the patients for participating in this study.

The authors report no additional financial or other relationship relevant to the subject of this article.

Corresponding author and reprints: Karen K. Miller, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, MA 02114 (e-mail: