Evidence map›Paper›PMID 40294815›Full record

ArticleContemporary clinical trials2025

Study protocol for a randomized, placebo-controlled, double-masked mechanistic clinical trial of transdermal estrogen replacement in hypoestrogenic eating disorders to explore the role of estrogen on cognitive flexibility and reward processing.

Lauren Breithaupt, Meghan Slattery, Meghan Lauze, Felicia Petterway, Lauren Lindman, Mia Cravitz, Sarah Naticchia, Siddarth Seenivasa, Macy Powers, Kristin N Javaras and 12 more

Abstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Contemporary clinical trials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
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4 · The record

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5 · Who and what money

Authors and funding

22 authors.

Lauren BreithauptDepartment of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Eating Disorders Clinical and Research Program, Massachusetts General Hospital, MA, USA; Mass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Meghan SlatteryMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Meghan LauzeMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Felicia PetterwayMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Lauren LindmanMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Mia CravitzDepartment of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Mass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Sarah NaticchiaMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard University, Department of Neuroscience, Cambridge, MA, USA.
Siddarth SeenivasaMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Macy PowersMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA.
Kristin N JavarasDivision of Women's Mental Health, McLean Hospital, Belmont, MA, USA; Klarman Eating Disorders Center, McLean Hospital, Belmont, MA, USA.
David J AlperovitzKlarman Eating Disorders Center, McLean Hospital, Belmont, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Judith HalperinDivision of Women's Mental Health, McLean Hospital, Belmont, MA, USA; Klarman Eating Disorders Center, McLean Hospital, Belmont, MA, USA.
Esther DechantEating Disorders Clinical and Research Program, Massachusetts General Hospital, MA, USA; Mass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Klarman Eating Disorders Center, McLean Hospital, Belmont, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Jennifer J ThomasDepartment of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Eating Disorders Clinical and Research Program, Massachusetts General Hospital, MA, USA; Mass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Elizabeth A LawsonMass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Hang LeeDivision of Biostatistics, Massachusetts General Hospital, Boston, MA, USA.
Diego A PizzagalliDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA; McLean Imaging Center, McLean Hospital, Belmont, MA, USA.
Adrienne L RomerDepartment of Psychology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Poornima KumarDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.
Franziska PlessowDepartment of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Madhusmita MisraDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Kamryn T EddyDepartment of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Eating Disorders Clinical and Research Program, Massachusetts General Hospital, MA, USA; Mass General Brigham Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: keddy@mgh.harvard.edu.

Funding

The Role of Estrogen in the Neurobiology of Eating Disorders: A Study of Cognitive Flexibility and Reward in Eating DisordersR01MH116205 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI EDDY, KAMRYN T, MISRA, MADHUSMITA · 2019 to 2023
$4.7M
Estrogen's Neuroprotective Effects on the Brain-Barrier in Restrictive Eating DisordersK23MH127465 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Lauren Breithaupt · 2022 to 2026
$793k
NIMH NIH HHS K23 MH127465NIMH NIH HHS R01 MH116205Wellcome Trust
6 · The paper itself

Abstract

backgroundRestrictive eating disorders (EDs) are associated with cognitive inflexibility, reduced reward responsiveness, and tendency to favor delayed rewards, which contribute to illness maintenance and poor outcomes. Low estrogen is common in EDs and has been linked to poor cognitive flexibility and reward processing in other conditions. We describe a randomized controlled double-masked trial of short-term (12 weeks) transdermal estrogen (100 μg 17-β) replacement versus placebo to test estrogen-effects on cognitive flexibility, reward responsiveness, delay discounting, and ED pathology in females with EDs and low estrogen (ED-LE).

methodsParticipants will include N = 120 females with ED-LE (14-35 years) with clinical, neuropsychological, and neural assessments occurring at baseline, eight weeks, and 12 weeks.

resultsPrimary outcomes will include between-group differences in 8-week change in cognitive flexibility, reward responsiveness, and delay discounting, and between-group differences in 12-week change in ED pathology. Secondary outcomes will include between-group differences in 8-week change in neural activation during cognitive flexibility and reward-related functional magnetic resonance imaging paradigms and mediation effects of 8-week change in cognitive flexibility, reward responsiveness, and delay discounting on 12-week change in ED pathology.

conclusionWe hypothesize that estrogen replacement will (1) increase cognitive flexibility, reward responsiveness, and delay discounting, and (2) reduce ED pathology; and (3) 8-week changes in cognitive flexibility, reward responsiveness, and delay discounting will mediate 12-week changes in ED pathology. These data will systematically probe the role of estrogen in key neurocognitive features associated with poor ED outcomes to guide development of novel interventions for this population.

Indexed as

CognitionEstrogen Replacement TherapyEstrogensFeeding and Eating DisordersRewardAdministration, CutaneousAdolescentAdultCognitive FlexibilityDelay DiscountingDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingRandomized Controlled Trials as TopicYoung AdultEstrogensAnorexia nervosaAtypical anorexia nervosaCognitive flexibilityDelay discountingEating disorderEstrogenReward responsiveness

Identifiers

PMID40294815
PMCPMC12403050

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.