Estradiol's Effect on Brain Volume and Connectivity

NCT ID: NCT06312033

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2021-12-31

Brief Summary

Ovarian hormones are not only modulators of cognitive function, emotion regulation and mental health, but also seem to affect brain plasticity and functional connectivity, During the menstrual cycle, women experience cyclic fluctuation of the ovarian hormone estradiol, which is closely associated with neuroplasticity/changes in brain structure in regions with high estradiol receptor density, such as the amygdala, hippocampus/parahippocampus, anterior cingulate cortex (ACC), striatum, and prefrontal cortex (PFC). Further functional connectivity between these areas seems to be associated with hormonal changes dependent on the menstrual cycle phase. But next to estradiol, also other hormones like progesterone fluctuate across the menstrual cycle. In the past, effects of ovarian hormone levels were often investigated in combination. However, one way to disentangle the impact of estradiol from that of other hormones on neuroplasticity, emotion regulation and mood states, can be the experimental increase of estradiol via estradiol administration. In this double-blinded within-subject study, women were administered either estradiol valerate or placebo during the early follicular phase (thus when ovarian hormone concentrations are low) before undergoing neuroimaging.

Parts of the study are already described in Rehbein et al., 2021 and 2022.

Detailed Description

In this project the investigators wanted to assess women with/without experimentally elevated estradiol (E2) levels in order to understand E2's effect on volume and resting state functional connectivity. Thus, women underwent fMRI (functional magnetic resonance imaging) scanning twice (with/without elevated E2) to deduce underlying neuronal activation. All participants underwent a structured assessment including demographical data, psychological/clinical data, e.g., structured clinical interview, anxiety traits, depression, emotion regulation traits, self-esteem as well as cognitive abilities, e.g., verbal intelligence, cognitive flexibility) and two (f)MRI measurements (T1/T2, separated by at least 2-3 months), including resting-state and anatomical scans as well as a behavioural emotion regulation task. At T1/T2 either E2 valerate or placebo was administered in a double-blinded, counterbalanced, randomized order.

E2 valerate administration: To experimentally elevate E2 concentrations each woman has received 6mg on two consecutive days (total 12mg) of E2 valerate (Progynova21©) Administration of E2 has been randomly distributed, so that women either received placebo (i.e. leading to an early follicular phase with low ovarian hormone levels) or E2 (i.e. leading to an early follicular phase with high E2 levels) first. Functional resting-state and anatomical data, emotion regulation performance, state anxiety, mood and depression scores have been acquired after the second pill intake. During the emotion regulation task women were asked to either (a) passively view aversive pictures or (b) down regulate their emotional response by e.g. changing their perspective on the picture and then rate their emotional state.

To assess changes in hormone concentrations (E2, progesterone, testosterone) blood samples were obtained before the first and after the second pill intake.

Conditions

Emotion Regulation; Estradiol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

naturally cycling women starting with placebo

naturally cycling women during early follicular phase starting with placebo (order was randomly selected)

Group Type: EXPERIMENTAL

Estradiol Valerate

Intervention Type: DRUG

To elevate estradiol levels each woman has received 6mg on two consecutive days (total 12mg) of estradiol valerate (Progynova21©)

Placebo

Intervention Type: DRUG

Placebo (blue-colored hard gelatine capsules completely filled with a mixture of 99.5% mannitol and 0.5% Aerosil (fumed silica)) has been administered (placebo-controlled condition)

naturally cycling women starting with estradiol

naturally cycling women during early follicular phase starting with estradiol (order was randomly selected)

Group Type: EXPERIMENTAL

Estradiol Valerate

Intervention Type: DRUG

To elevate estradiol levels each woman has received 6mg on two consecutive days (total 12mg) of estradiol valerate (Progynova21©)

Placebo

Intervention Type: DRUG

Placebo (blue-colored hard gelatine capsules completely filled with a mixture of 99.5% mannitol and 0.5% Aerosil (fumed silica)) has been administered (placebo-controlled condition)

Interventions

Estradiol Valerate

To elevate estradiol levels each woman has received 6mg on two consecutive days (total 12mg) of estradiol valerate (Progynova21©)

Intervention Type: DRUG

Placebo

Placebo (blue-colored hard gelatine capsules completely filled with a mixture of 99.5% mannitol and 0.5% Aerosil (fumed silica)) has been administered (placebo-controlled condition)

Intervention Type: DRUG

Other Intervention Names

Progynova21

Eligibility Criteria

Inclusion Criteria

• Women, biologically female (assigned sex at birth)
• regular menstrual cycle lasting between 26 and 32 days
• right handedness

Exclusion Criteria

• present or past mental, neurological or endocrine disorders
• use of hormonal contraceptives during the last six months
• any other medication intake,
• or past and present pregnancies
• Intake of antidepressants or neuroleptics
• contraindication for MRI

• 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
• Neurological disease or injury
• Moderate or severe head injury
• Restricted vision

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Tübingen

UNKNOWN

Sponsor Role: collaborator

German Research Foundation

OTHER

Sponsor Role: collaborator

Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN)

UNKNOWN

Sponsor Role: collaborator

International Research Training Group 2804

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Birgit Derntl, Prof.

Role: PRINCIPAL_INVESTIGATOR

Departement of Psychiatry & Psychotherapy

Locations

University of Tuebingen; Department of Psychiatry & Psychotherapy

Tübingen, Baden-Wurttemberg, Germany

Countries

Germany

Other Identifiers

MRTG_P01

Identifier Type: -

Identifier Source: org_study_id