NCT07831499 · University of Colorado, Denver
Cyclic vs. Constant Estradiol: Regimens' Effects on Brain Health
(CEREBRA)
What this study is about
The purpose of this study is to learn more about how estradiol patch treatment affects brain processes, health, and wellbeing.
View original scientific description
The purpose of this study is to learn more about how estradiol patch treatment affects brain processes, health, and wellbeing.
Interventions
DRUG
Cyclic Estradiol
Participants 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.
DRUG
Continuous Estradiol
Participants 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.
Primary outcome measures
Change in Dorsolateral Prefrontal Cortex (dlPFC) activation during working memory task in women receiving either cyclic or continuous estradiol administration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
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.
Change from baseline in extracellular vesicle concentration.
Time frame: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
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.
Change from baseline in extracellular vesicle size.
Time frame: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
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.
Change from baseline in extracellular vesicle zeta potential.
Time frame: Baseline, Days 1-4, Days 21-24, and approximately 12 weeks after treatment initiation
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.
Change in C-reactive protein concentration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
Serum C-reactive protein concentration measured using the Meso Scale Discovery (MSD) V-PLEX Neuroinflammation Panel.
Change in interleukin concentration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
Interleukin concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in cytokine concentration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
Cytokine concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in chemokine concentration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
Chemokine concentration measured using the MSD V-Plex Neuroinflammation Panel.
Change in growth factor concentration.
Time frame: Baseline and approximately 12 weeks after initiation of study treatment
Growth factor concentration measured using the MSD V-Plex Neuroinflammation Panel.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
- Have estradiol level below 40 pg/ml and follicle stimulating hormone (FSH) level above 25 at Van Visit Day 1. Individuals with high estradiol or low FSH levels may be retested, and eligibility determination will be at the discretion of the Principal Investigator (PI).
- Report final menstrual period (FMP) occurred between 12 months and 48 months at the time of screening.
- Right-handed.
- Participants are required to have at least some college education. Setting a minimum education level reduces variability due to educational disparities and supports the validity and interpretability of cognitive performance data. These tasks involve higher-order verbal learning, memory, and executive processes that can be strongly influenced by educational attainment. The investigators will re-evaluate this criterion in future larger-scale studies as resources allow.
Exclusion criteria
- 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.
- Chronic use of steroid medication and other medications that could impact immune function and alter glucocorticoid levels.
- Inability to forgo use of non-steroidal anti-inflammatory medications for 4 days prior to the Baseline Visit, Van Visits, and Follow Up Visit.
- Any current or recent medical, psychiatric or social condition which, in the investigator's opinion, is likely to interfere with the conduct of the study, confound the interpretation of study results, or endanger the subject's well-being.
- Use of systemic hormone therapy (including but not limited to estradiol, progesterone, testosterone, combined hormonal contraceptives, and other systemic hormonal preparations) within 3 months prior to study enrollment. Use of local vaginal estrogen therapy (e.g., vaginal cream or Estring) is permitted. For participants with a history of systemic hormone use, the study investigator may review treatment history to determine whether postmenopausal status can be confirmed.
- History of suicidal behavior within the past 2 years
- Undiagnosed abnormal genital bleeding.
- Known, suspected, or history of breast cancer.
- Active deep vein thrombosis, pulmonary embolism, or history of these conditions.
- History of cardiovascular disease
- Known liver dysfunction or disease.
- Needle phobia or history of vasovagal response to phlebotomy.
- History of clinically relevant claustrophobia or inability to tolerate a scanning environment in the past.
- Metal in body unsafe for magnetic resonance imaging (MRI) or other conditions that would make MRI unsafe for participants (i.e., aneurysm clip, cardiac pacemaker, etc.).
- Current treatment with Central nervous system (CNS) depressants (e.g., opioids, benzodiazepines).
- Treatment with corticosteroids within the past 30 days.
- Known allergy to progesterone or peanut allergy.
- Any history of chemotherapy as negative effects on cognitive performance have been reported for years post cessation of treatment (Guida et al., 2021; Koppelmans et al., 2012).
Where
- Aurora, Colorado
Collaborators
Pedersen Foundation
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 21, 2026 · Source of record for eligibility and locations