Estradiol (E2) Vs. Placebo (PLAC)NCT06773429
Estradiol and Brain Age
An observational study of Estradiol (E2) Vs. Placebo (PLAC) and Estradiol, run by International Research Training Group 2804 at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 to 32 years, women only
- Conditions the study is for
- Estradiol (E2) Vs. Placebo (PLAC), Estradiol
- What is being tested?
- E2 Valerate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteGermany
- Study dates
- 1 Aug 2018to 31 Jul 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 32 years
- Women only
- No healthy volunteers
- Adult
Study population: The study population mainly consists of residents of Tübingen and surrounding areas.
Who may be able to join
- Biologically females (assigned sex at birth)
- Regular menstrual cycle lasting between 26 and 35 days
- Right-handedness
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
University of Tuebingen; Department of Psychiatry & Psychotherapy
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: 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.
Read the 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.
- Conditions
- Estradiol (E2) Vs. Placebo (PLAC), Estradiol
- Being tested
- E2 Valerate, Placebo
- Keywords
- Neuroprotection, brain-age, neuroimaging, menstrual cycle, sex hormones, estradiol, women's mental health
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E2 ValerateDrug
To experimentally elevate E2 levels females received 6mg of E2 valerate (Progynova21©) on two consecutive days (in total 12mg).
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Naturally cycling women | Naturally cycling women during the early follicular menstrual cycle phase Receives: Drug: E2 Valerate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between E2 administration and brain age
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.
Measured: 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.
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.
Measured: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Secondary outcomes (7)
Association between progesterone level and brain age.
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.
Measured: 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
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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.
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.
Measured: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2025
- Study start1 Aug 2018
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Estradiol (E2) Vs. Placebo (PLAC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Research Training Group 2804
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Tuebingen, DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation), Mini Research Training Group (MRTG)
- Responsible party
- Sponsor
- Investigators
- Birgit Derntl, Prof., Principal investigator, Departement of Psychiatry & Psychotherapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06773429
- Sponsor's protocol ID
- E2BrainAge
- Status last verified
- Jan 2025
- First submitted
- 8 Jan 2025
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estradiol's Effect on Brain Age
- ClinicalTrials.gov ID
- NCT06773429
- Acronym / sponsor ID
- E2BrainAge
- Conditions
- Estradiol (E2) Vs. Placebo (PLAC), Estradiol
- Keywords
- Neuroprotection, brain-age, neuroimaging, menstrual cycle, sex hormones, estradiol, women's mental health
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- International Research Training Group 2804University, hospital or other
- Collaborators
- University Hospital Tuebingen, DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation), Mini Research Training Group (MRTG)
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 14 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Naturally cycling women | – | Drug: E2 Valerate, Drug: PlaceboNaturally cycling women during the early follicular menstrual cycle phase |
Who may qualify
- Ages
- 19 to 32 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study population mainly consists of residents of Tübingen and surrounding areas.
Key inclusion criteria (3 listed)
- Biologically females (assigned sex at birth)
- Regular menstrual cycle lasting between 26 and 35 days
- Right-handedness
Key exclusion criteria (11 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E2 ValerateTo experimentally elevate E2 levels females received 6mg of E2 valerate (Progynova21©) on two consecutive days (in total 12mg). | Drug | Naturally cycling women |
| PlaceboPlacebo 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. | Drug | Naturally cycling women |
Primary outcome
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.
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.
7 secondary outcomes
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
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
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Birgit Derntl, Prof. principal investigator
Departement of Psychiatry & Psychotherapy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Estradiol (E2) Vs. Placebo (PLAC) and Estradiol, run by International Research Training Group 2804 at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.