Anorexia nervosa is a disease characterized by severe loss of weight with increased morbidity. The disorder is associated with multiple severe medical consequences, resulting in the highest mortality rate among psychiatric disorders. The disorder represents an important public health concern, given its significant incidence among adolescents and young adults. Treatment strategies used to date have been largely ineffective and there is a critical need to develop and explore novel therapeutic paradigms. Psychiatric co-morbidities including anxiety and depressions are common in patients with anorexia nervosa. Studies have also shown that co- morbid anxiety and depressive symptoms are often associated with eating disorder persistence and outcome, and, that severe depression and higher levels of anxiety predict poor eating disorder outcome. We have shown that a previously unrecognized endocrine deficiency, low levels of the hormone testosterone is common in women with anorexia nervosa and directly related to disease severity. In preliminary data, physiologic testosterone replacement is associated with a reduction in Eating Disorders Inventory-2 scores, and increase in BMI and decreases in psychiatric co-morbidities. We hypothesize that testosterone is an effective means to reduce to major co-morbidities, depression and anxiety and in doing so will lead to an improvement in Eating Disorders Examination scores and overall improvement in core anorexia nervosa symptoms. The overall goal of this study is to determine the efficacy of low-dose testosterone replacement in the treatment of anorexia nervosa. This will be accomplished by physiologic testosterone administration through a novel transdermal delivery system. Patients will be randomized to either testosterone or a placebo patch. The main endpoints will be BMI, Eating Disorders Inventory-2 scores, depression and anxiety scores. The demonstration of testosterone efficacy in this population would represent a novel strategy to treating this disorder.

Public Health Relevance

Anorexia nervosa is a disease with increased morbidity and has the highest mortality rate of any psychiatric disease and treatment strategies used to date have been largely ineffective. Low levels of the hormone testosterone occur in this disease and physiologic testosterone replacement is associated with a reduction core symptoms and associated morbidities. We propose to investigate whether long-term testosterone replacement improves symptoms of anorexia nervosa.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1-ERB-N (06))
Program Officer
Chavez, Mark
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Dichtel, Laura E; Lawson, Elizabeth A; Schorr, Melanie et al. (2018) Neuroactive Steroids and Affective Symptoms in Women Across the Weight Spectrum. Neuropsychopharmacology 43:1436-1444
Tabari, Azadeh; Torriani, Martin; Miller, Karen K et al. (2017) Anorexia Nervosa: Analysis of Trabecular Texture with CT. Radiology 283:178-185
Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G et al. (2017) Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab 102:57-68
Schorr, Melanie; Thomas, Jennifer J; Eddy, Kamryn T et al. (2017) Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5. Int J Eat Disord 50:343-351
Kandemir, Nurgun; Becker, Kendra; Slattery, Meghan et al. (2017) Impact of low-weight severity and menstrual status on bone in adolescent girls with anorexia nervosa. Int J Eat Disord 50:359-369
Bachmann, Katherine N; Bruno, Alexander G; Bredella, Miriam A et al. (2016) Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women. J Bone Miner Res 31:281-8
Gill, Corey M; Torriani, Martin; Murphy, Rachel et al. (2016) Fat Attenuation at CT in Anorexia Nervosa. Radiology 279:151-7
Eddy, Kamryn T; Lawson, Elizabeth A; Meade, Christina et al. (2015) Appetite regulatory hormones in women with anorexia nervosa: binge-eating/purging versus restricting type. J Clin Psychiatry 76:19-24
Faje, Alexander T; Fazeli, Pouneh K; Miller, Karen K et al. (2014) Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord 47:458-66
Bredella, Miriam A; Gill, Corey M; Keating, Leigh K et al. (2013) Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity. Obesity (Silver Spring) 21:2458-64

Showing the most recent 10 out of 15 publications