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NCT Number: NCT03740204

The Role of Estrogen in the Neurobiology of Eating Disorders

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Eating Disorders Amenorrhea Anorexia Nervosa Feeding and Eating Disorders Hypoestrogenemia Menstruation Disturbances Mental Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Age range

14 year–35 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

17-β estradiol transdermal patches with cyclic progesterone

Drug

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 patch and pill

Drug

Placebo patch and pill

Primary outcomes

  1. Change in inhibition-switching performance on the Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWIT) with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  2. Change in Temporal Experience of Pleasure Scale (TEPS) Consummatory Pleasure score (Range: 8-48; direction: Higher values indicate more pronounced consummatory pleasure/better outcome) with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  3. Change in delay discounting parameter k using the Monetary Choice Questionnaire with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  4. Change in Eating Disorder Inventory-3 (EDI-3) Body Dissatisfaction score (Range: 0-36; direction: Higher values indicate more pronounced body dissatisfaction/worse outcome) with 17-β estradiol versus placebo

    Time frame: Baseline to 12 weeks

  5. Change in EDI-3 Drive for Thinness score (Range: 0-28; direction: Higher values indicate more pronounced drive for thinness/worse outcome) with 17-β estradiol versus placebo

    Time frame: Baseline to 12 weeks

Secondary outcomes

  1. Change in functional magnetic resonance imaging (fMRI) activation of the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) during a task switching paradigm with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  2. Change in fMRI activation of the ventromedial prefrontal cortex (VMPFC) and ventral striatum in response to reward receipt with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  3. Change in fMRI activation of the VMPFC and ventral striatum during delay discounting with 17-β estradiol versus placebo

    Time frame: Baseline to 8 weeks

  4. Change in the Eating Disorder Examination (EDE) Dietary Restraint subscale (Range: 0-6; direction: Higher values indicate more pronounced dietary restraint/worse outcome) with 17-β estradiol versus placebo

    Time frame: Baseline to 12 weeks

  5. Change in caloric intake by 4-day food diary with 17-β estradiol versus placebo

    Time frame: Baseline to 12 weeks

Sponsors and collaborators

Lead sponsor

Massachusetts General Hospital

Other

Registry information

Official study title

The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating Disorders

Important dates

Study start
2019
Primary completion
2025
Study completion
2026
First posted
Nov 14, 2018
Registry last updated
May 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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