Estradiol and Brain Age

NCT06773429 | Completed

• 1 other identifier: E2BrainAge
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Estradiol (E2) Vs. Placebo (PLAC); Estradiol

Keywords

Neuroprotection; brain-age; neuroimaging; menstrual cycle; sex hormones; estradiol; women's mental health

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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.

  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

  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.

  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

  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

  Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans

Study Arms (1)

Naturally cycling women

Naturally cycling women during the early follicular menstrual cycle phase

Drug: E2 Valerate; Drug: Placebo

Interventions

E2 Valerate DRUG

To experimentally elevate E2 levels females received 6mg of E2 valerate (Progynova21©) on two consecutive days (in total 12mg).

Naturally cycling women

Placebo DRUG

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.

Naturally cycling women

Eligibility Criteria

• Age: 19 Years - 32 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• International Research Training Group 2804: lead
• University Hospital Tübingen: collaborator
• DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation): collaborator
• Mini Research Training Group (MRTG): collaborator

Study Sites (1)

University of Tuebingen; Department of Psychiatry & Psychotherapy

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Study Officials

• Birgit Derntl, Prof.

  Departement of Psychiatry & Psychotherapy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 14, 2025
• Study Start: August 1, 2018
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

DE (1)