Neurobiology of Bulimia Nervosa
Condition: Bulimia Nervosa
MeSH terms: Bulimia; Bulimia Nervosa
Study type: Interventional
Phase: Phase 2

Summary: 
      This pilot study experimentally manipulates ovarian hormones to examine the direct impact of
      estrogen (E2) and progesterone (P4) on binge eating symptom burden and the behavioral reward
      response in women with bulimia nervosa (n=15). This is completed by taking medications that
      change ovarian hormone levels. This line of research could lead to the development of
      pharmacological interventions developed to target specific areas of the brain, brain
      receptors, or pathways identified to be involved in the mechanism underlying ovarian hormone
      change and binge eating.
    

Detailed description: 
      Eating disorders (EDs) affect 15 million women in the United States and have one of the
      highest mortality rates of any mental illness. Despite this, the underlying neurobiology
      remains poorly understood. EDs predominantly occur in women, and the frequency of certain
      symptoms change in a predictable pattern over the menstrual cycle; specifically, symptom
      changes appear to be triggered by normal fluctuations in the ovarian hormones estradiol (E2)
      and progesterone (P4).

      The objective of this study is to examine the direct and mechanistic role of E2 and P4 on
      binge eating in women with bulimia nervosa (BN; n = 15). The experimental design parallels an
      established design developed to determine the hormonal triggers of premenstrual dysphoric
      disorder and depression: temporarily stopping the menstrual cycle using a
      Gonadotropin-releasing hormone (GnRH) agonist (Lupron) and addback E2 and P4 independently in
      a double-blind crossover design. The overarching hypothesis is that BN represents a
      hormone-sensitive phenotype, and this sensitivity is modulated by E2's effects on aspects of
      the reward response such that reward-motivated behaviors increase in the context of low E2.
      This line of research will provide direction for future research addressing neuroendocrine,
      neurobiological, and brain activity and function in BN. To date, there are no medications
      that have been developed specifically for the treatment of individuals with BN.

      Our specific aims are to:

      Aim 1: Quantify the direct effect of E2 and P4 on binge eating in women with BN.

      Aim 2: Determine the effect of E2 on reward response in women with BN.

      Aim 3: Examine the association between reward response and binge eating before and after E2
      addback.
    

Intervention name(s): Estradiol; Micronized progesterone; Leuprolide Acetate; Placebo Oral Capsule
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): During estradiol administration, 2mg of estradiol is given twice daily via oral capsule.; During progesterone administration, 200mg of progesterone is given twice daily via oral capsule.; Initial 3.75 mg intramuscular injection administered approximately Day 6 of menstrual cycle and then monthly thereafter for a total of 3 months.; Placebo is administered during the addback phase when participants are not taking active medication. Placebo is given so that medication administration occurs throughout the entire 8-week addback period in order to blind participants to when and for how long they are on the active medication.
Other intervention name(s): E2; Estrace; P4; Prometrium; Lupron Depot; Sugar pill
Intervention MeSH terms: Leuprolide; Estradiol; Progesterone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: bulimia nervosa; binge eating; eating disorder; estrogen