The Role of Estrogen in the Neurobiology of Eating Disorders

Purpose

This is a randomized, double blind, placebo-controlled study of the effects of transdermal estradiol versus placebo on cognitive flexibility, reward processing, and eating disorder pathology in hypoestrogenemic female adolescents and young adults (ages 14-35 years) with an eating disorder characterized by extreme dietary restriction and/or excessive exercise. Subjects will be randomized 1:1 to 12 weeks of transdermal estradiol with cyclic progesterone or placebo patches and cyclic placebo pills. Study visits include a screening visit to determine eligibility and visits at baseline, 8 weeks, and 12 weeks. Study procedures comprise behavioral, neuroimaging, and endocrine assessments.

Conditions

  • Eating Disorders
  • Hypoestrogenemia

Eligibility

Eligible Ages
Between 14 Years and 35 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Female - 14-35 years - Bone age ≥13.5 years (applicable only for participants <16 years) - Clinically significant eating disorder characterized by restriction and/or excessive exercise and high drive for thinness - Hypoestrogenemia: Oligo-amenorrhea defined as lack of menses for ≥3 months within a 6-month period of oligomenorrhea (cycle length ≥5 weeks) or absence of menses at >15 years if premenarchal or low estradiol levels evaluated by the study physician - Low or normal weight defined by a body mass index that is <85th percentile for 14-18 year olds and a body mass index <25 kg/m2 for adults

Exclusion Criteria

  • Suicidal ideation where outpatient treatment is determined unsafe by study clinician - Other causes of oligo-amenorrhea, unless a study clinician determines that missed menstrual periods are more likely a consequence of restrictive eating - Medications that contain estrogen ± progesterone within the past 3 months - Levonorgestrel-releasing intrauterine device if subject is unable to provide two to three weekly blood samples for estradiol of if estradiol levels are determined to be too high by study doctor - Neurological or psychiatric disorders that may impact neural circuitry of interest - Lifetime history of seizure disorder or electroconvulsive therapy - Pregnancy/breastfeeding - Gastrointestinal tract surgery - Contraindications to estrogen use - Any other significant illness or condition that the investigator determines could interfere with study participation or safety or put the subject at any unnecessary risk

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
17-β estradiol with cyclic progesterone
  • Drug: 17-β estradiol transdermal patches with cyclic progesterone
    17-β estradiol transdermal patches (100 mcg 17-β estradiol/day) with cyclic progesterone (200 mg micronized progesterone daily for 12 days every month)
Placebo Comparator
Placebo
  • Drug: Placebo patch and pill
    Placebo patch and pill

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Madhusmita Misra, M.D., M.P.H.
617-726-5790
mmisra@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Madhusmita Misra, M.D., M.P.H.
617-726-5790
mmisra@mgh.harvard.edu