Cyclic vs. Constant Estradiol: Regimens' Effects on Brain Health
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexFemale
Age38-60
SponsorUniversity of Colorado, Denver
About this trial
The purpose of this study is to learn more about how estradiol patch treatment affects brain processes, health, and wellbeing.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Ages 38 to 60.
Ability to give written informed consent.
Fluent in written and verbal English, though may use Spanish to speak with study staff if preferred. This criterion is based on methodological necessity and feasibility, to ensure participants can accurately understand task instructions and questionnaire items which are available only in English for this pilot study.
Participants must be up to date on age-appropriate cancer screening. Specifically, participants must have had a pap smear within the previous 3 years and a mammogram within the previous 2 years (American College of Obstetricians and Gynecologists, 2026; Health Resources and Services Administration, n.d.). Documentation may be requested to verify screening history.
Disqualifiers
Current psychiatric diagnosis as assessed by the Mini International Neuropsychiatric Interview (MINI, Sheehan et al., 1998).
Active psychiatric illness within the previous 12 months or lifetime diagnosis of a psychotic disorder.
Current use of antipsychotic medications or mood stabilizers. Participants may have sporadic use of benzodiazepines during the course of the study as long as they can forgo use at least 4 days prior to study procedures.
Current or history of substance use disorder within previous 12 months. However, individuals with mild disorders, disorders solely limited to cannabis or alcohol, and/or those who have achieved close to one year of remission may be eligible at the discretion of the PI.
Trial design
Design model
Parallel
Treatments tested in this trial
Cyclic Estradiol
DrugParticipants randomized to the cyclic estradiol group apply a transdermal estradiol patch delivering 100 mcg/day for 5 days every 21 days over approximately 12 weeks. The patch is removed on the fifth day of each treatment cycle. The final patch is worn for 7 days.
Continuous Estradiol
DrugParticipants randomized to the continuous estradiol group apply a transdermal estradiol patch delivering 100 mcg/day continuously for approximately 12 weeks. The patch is replaced every 6 days and worn throughout the treatment period. The final patch is worn for 7 days.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Cyclic EstradiolExperimental treatment 1 intervention
Group B: Continuous EstradiolExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in Dorsolateral Prefrontal Cortex (dlPFC) activation during working memory task in women receiving either cyclic or continuous estradiol administration.
Description: Dorsolateral prefrontal cortex (dlPFC) activation will be measured during performance of the letter N-back task using functional magnetic resonance imaging (fMRI). Change scores will be calculated from baseline to follow-up.
Time frame
Baseline and approximately 12 weeks after initiation of study treatment2
Change from baseline in extracellular vesicle concentration.
Extracellular vesicle (EV) concentration will be measured from plasma samples and reported as particles per milliliter (particles/mL). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Time frame
Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation3
Change from baseline in extracellular vesicle size.
Extracellular vesicle (EV) size will be measured from plasma samples and reported in nanometers (nm). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Time frame
Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation4
Change from baseline in extracellular vesicle zeta potential.
Extracellular vesicle (EV) zeta potential will be measured from plasma samples and reported in millivolts (mV). Changes from baseline will be assessed following cyclic or continuous estradiol administration.
Time frame
Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiationSecondary outcomes
1
Change in executive function symptoms on the Brown Attention-Deficit Disorder Scale (BADDS).
The BADDS is a validated 40-item self-report measure of executive function difficulties. Total scores range from 0 to 120, with higher scores indicating greater executive dysfunction.
Time frame
Baseline and approximately 12 weeks after initiation of study treatment2
Change in perceived stress on the Perceived Stress Scale (PSS).
The PSS is a 10-item self-report measure of perceived stress. Total scores range from 0 to 40, with higher scores indicating greater perceived stress.
Time frame
Baseline and approximately 12 weeks after initiation of study treatment3
Change in depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).
The CES-D is a 20-item self-report measure of depressive symptoms. Total scores range from 0 to 60, with higher scores indicating greater severity of depressive symptoms.
Time frame
Baseline and approximately 12 weeks after initiation of study treatment4
Change in anxiety symptoms on the Generalized Anxiety Disorder-7 (GAD-7).
The GAD-7 is a 7-item self-report measure of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity.
Time frame
Baseline and approximately 12 weeks after initiation of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
Pedersen Foundation
Collaborator
Source ClinicalTrials.gov