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Impact of Physiologic Estrogen Replacement on Anxiety Symptoms, Body Shape Perception, and Eating Attitudes in Adolescent Girls With Anorexia Nervosa: Data From a Randomized Controlled Trial

Madhusmita Misra, MD, MPH; Debra K. Katzman, MD;Nara Mendes Estella, BA; Kamryn T. Eddy, PhD; Thomas Weigel, MD;Mark A. Goldstein, MD; Karen K. Miller, MD; and Anne Klibanski, MD

Published: August 15, 2013

Article Abstract

Objective: Anorexia nervosa is characterized by low weight, aberrant eating attitudes, body image distortion, and hypogonadism. Anxiety is a common comorbid condition. Estrogen replacement reduces anxiety in animal models, and reported variations in food intake across the menstrual cycle may be related to gonadal steroid levels. The impact of estrogen replacement on anxiety, eating attitudes, and body image has not been reported in anorexia nervosa. We hypothesized that physiologic estrogen replacement would ameliorate anxiety and improve eating attitudes without affecting body image in anorexia nervosa.

Method: Girls 13-18 years old with anorexia nervosa (DSM-IV) were randomized to transdermal estradiol (100 μg twice weekly) with cyclic progesterone or placebo patches and pills for 18-months, between 2002 and 2010. The State-Trait Anxiety Inventory for Children (STAIC), the Eating Disorders Inventory-2 (EDI-2), and the Body Shape Questionnaire (BSQ-34) were administered. 72 girls completed these measures at baseline (n = 38 [girls receiving estrogen] and n = 34 [girls receiving placebo]) and 37 at 18 months (n = 20 [girls receiving estrogen] and n = 17 [girls receiving placebo]). The primary outcome measure was the change in these scores over 18 months.

Results: Estrogen replacement caused a decrease in STAIC-trait scores (−3.05 [1.22] vs 2.07 [1.73], P = .02), without impacting STAIC-state scores (−1.11 [2.17] vs 0.20 [1.42], P = .64). There was no effect of estrogen replacement on EDI-2 or BSQ-34 scores. Body mass index (BMI) changes did not differ between groups, and effects of estrogen replacement on STAIC-trait scores persisted after controlling for BMI changes (P = .03). Increases in serum estradiol were significantly associated with decreases in STAIC-trait scores (Spearman ρ = −0.45, P = .03).

Conclusions: Estrogen replacement improved trait anxiety (the tendency to experience anxiety) but did not impact eating attitudes or body shape perception.

Trial Registration: identifier: NCT00088153

J Clin Psychiatry 2013;74(8):e765-e771

Submitted: January 11, 3013; accepted March 22, 2013 (doi:10.4088/JCP.13m08365).

Corresponding author: Madhusmita Misra, MD, MPH, BUL 457, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114 (

Volume: 74

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