NCT06312033

Estradiol's Effect on Brain Volume and Connectivity

Estradiol's Effect on Brain Volume and Connectivity in Naturally Cycling Women

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: International Research Training Group 2804 · Academic / Other
• Sex: Female
• Age: 19 Years – 35 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	Estradiol Valerate	To elevate estradiol levels each woman has received 6mg on two consecutive days (total 12mg) of estradiol valerate (Progynova21©)
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)

Timeline

• Start date: 2018-08-01
• Primary completion: 2019-07-31
• Completion: 2021-12-31
• First posted: 2024-03-15
• Last updated: 2024-03-15

Locations

1 site across 1 country: Germany