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
Abstract
Background: Restrictive 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 mcg 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). Methods: Participants 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. Results: Primary 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. Conclusion: We hypothesize that estrogen replacement will (1) increase cognitive flexibility, reward responsiveness,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 120 participants or records.
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