Clinical trial NCT06773429: Estradiol and Brain Age
Official title: Estradiol's Effect on Brain Age
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Estradiol (E2) Vs. Placebo (PLAC)
Estradiol
Keywords: Neuroprotection
brain-age
neuroimaging
menstrual cycle
sex hormones
estradiol
women&amp;#39;s mental health
Lead sponsor: International Research Training Group 2804
Sponsor class: OTHER
Collaborators: name: University Hospital Tübingen
name: DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation)
name: Mini Research Training Group (MRTG)
First posted: 2025-01-14
Enrollment: 32
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population mainly consists of residents of Tübingen and surrounding areas.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Association between E2 administration and brain age
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between E2 level and brain age.
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Secondary outcomes:
measure: Association between progesterone level and brain age.
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between testosterone level and brain age
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between subjective mood and brain age.
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between depression scores and brain age
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between anxiety scores and brain age
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between self-esteem and brain age
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
measure: Association between emotion-regulation and brain age.
timeFrame: Females were measured twice with at least two-three months apart; each time: approx. 10 minutes assessment of MRI-scans
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University of Tuebingen; Department of Psychiatry & Psychotherapy
state: BW
Study officials:
affiliation: Departement of Psychiatry & Psychotherapy
name: Birgit Derntl, Prof.
role: PRINCIPAL_INVESTIGATOR
References: