Estradiol and Brain Age

January 28, 2025 updated by: International Research Training Group 2804

Estradiol's Effect on Brain Age

The ovarian hormone estradiol (E2) is suspected to have a neuroprotective effect on the brain. Further, it is associated with mental health and brain plasticity, function and connectivity. During the menstrual cycle, women experience fluctuation of E2. This is closely associate with neuroplasticity in regions with high estradiol receptor density, such as the hippocampus, anterior cingulate cortex, amygdala, hypothalamus, or the striatum. In the current study we are interested on the effects of E2 on the brain age, indicated by the comparison between the chronological age and the predicted brain age. In a double-blind within-subject study design, naturally cycling females during their follicular menstrual cycle phase (when their endogenous ovarian hormone levels are low) were either administered estradiol valerate (E2) or a placebo (PLAC) to rapidly increase E2 levels independent of other cycling ovarian hormones. Structural brain scans were assessed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this project we assessed regularly cycling females in their early follicular menstrual cycle phase with/without experimentally elevated estradiol (E2) levels in order to examine E2's effect on the brain age. Thus, women were scanned twice in the MR-scanner (E2 vs. PLAC; separated by at least 2-3 months) to deduce underlying structural changes. E2 vs. PLAC were administered in a double-blind, counterbalanced, randomized order. E2 has been administered orally (in total 12mg; two doses à 6mg on two consecutive days). All participants additionally underwent a neuropsychological assessment (demographical data, psychological and clinical data: structured clinical interview, anxiety and depression traits, mood, verbal intelligence, cognitive flexibility, emotion regulation traits, self-esteem). Blood samples were taken to assess endogenous gonadal hormone levels before and after E2/PLAC intake.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • BW
      • Tuebingen, BW, Germany, 72076
        • University of Tuebingen; Department of Psychiatry & Psychotherapy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population mainly consists of residents of Tübingen and surrounding areas.

Description

Inclusion Criteria:

  • Biologically females (assigned sex at birth)
  • Regular menstrual cycle lasting between 26 and 35 days
  • Right-handedness

Exclusion Criteria:

  • Present or past mental, neurological or endocrine disorders, neurological or head injuries
  • Use of hormonal contraceptives during the last six months
  • Any other medication intake including intake of antidepressants or neuroleptics
  • Past and present pregnancies

  • Contraindication for MRI such as:

    • People with non-removable metal objects on or in the body
    • Tattoos if not MRI-incompatible according to expert guidelines
    • Pathological hearing or increased sensitivity to loud noises
    • Claustrophobia
    • Surgery less than three months ago
    • Restricted vision

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Naturally cycling women
Naturally cycling women during the early follicular menstrual cycle phase
Drug: E2 Valerate
To experimentally elevate E2 levels females received 6mg of E2 valerate (Progynova21©) on two consecutive days (in total 12mg).
Drug: Placebo
Placebo pills (blue-colored hard gelatine capsules filled with a mixture of 99.5% mannitol and 0.5% Aerosil (fumed silica)) have been administered for the placebo-controlled condition.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Association between E2 administration and brain age
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration. Predicted brain age during the E2- and the PLAC-condition will be compared to the chronological age.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between E2 level and brain age.
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and corresponding hormone levels. Association of E2-level increase with the difference between the predicted brain age and the chronological age ("brain-age-gap", BAG) will be compared.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Association between progesterone level and brain age.
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and corresponding hormone levels. Association of progesterone levels [nmol/l] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between testosterone level and brain age
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and corresponding hormone levels. Association of testosterone levels [nmol/l] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between subjective mood and brain age.
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and mood ratings. Association of mood ratings [Positive and negative affect PANAS, ratings from 1 to 5] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between depression scores and brain age
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and depression scores. Association of depression scores [Becks depression index BDI] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between anxiety scores and brain age
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and anxiety scores. Association of anxiety scores [State anxiety index STAI] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between self-esteem and brain age
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and self-esteem scores. Association of self-esteem scores [Rosenberg selfesteem] with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Association between emotion-regulation and brain age.
Time Frame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Assessed via anatomical MRI scans after E2 and PLAC administration and emotion-regulation scores. Association of emotion-regulation [Heidelberg form of emotion regulation HFRST and emotion regulation questionnaire ERQ] scores with the BAG [years] will be assessed.
Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
International Research Training Group 2804

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation)
University Hospital Tübingen
Mini Research Training Group (MRTG)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Birgit Derntl, Prof., Departement of Psychiatry & Psychotherapy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E2BrainAge

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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