Estradiol's Effect on Brain Volume and Connectivity in Naturally Cycling Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Impact of E2 concentration on brain structure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Neither participant or investigator knew the timepoint of drug or placebo administration. Pills were prepared by independent members of the university hospital.
入排标准
- 年龄范围
- 19 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women, biologically female (assigned sex at birth)
- •regular menstrual cycle lasting between 26 and 32 days
- •right handedness
排除标准
- •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
研究组 & 干预措施
naturally cycling women starting with placebo
naturally cycling women during early follicular phase starting with placebo (order was randomly selected)
干预措施: Estradiol Valerate (Drug)
naturally cycling women starting with placebo
naturally cycling women during early follicular phase starting with placebo (order was randomly selected)
干预措施: Placebo (Drug)
naturally cycling women starting with estradiol
naturally cycling women during early follicular phase starting with estradiol (order was randomly selected)
干预措施: Estradiol Valerate (Drug)
naturally cycling women starting with estradiol
naturally cycling women during early follicular phase starting with estradiol (order was randomly selected)
干预措施: Placebo (Drug)
结局指标
主要结局
Impact of E2 concentration on brain structure
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging
Brain structure (assessed via anatomical MRI scans, MPRAGE) will be compared between E2 and placebo conditions in regions of interest (ROI) (including amygdala, hippocampus/parahippocampus, ACC, striatum, and PFC).
Impact of E2 concentration and state emotion regulation on brain structure
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging (structure) and 20 minutes (emotion regulation task)
Brain structure (assessed via anatomical MRI scans, MPRAGE, in cm³) will be compared between E2 and placebo conditions in dependence of state emotion regulation ratings in ROIs (as above). State emotion regulation ratings obtained via the emotion regulation task (subjective rating ranging from -200 to 200).
Impact of E2 concentration and emotion regulation traits on brain structure
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging
Brain structure (assessed via anatomical MRI scans) will be compared between E2 and placebo conditions in dependence of emotion regulation traits in ROIs (as above). Emotion regulation traits assessed via the Heidelberg Form of Emotion Regulation (HFERST, ranging from 1 to 5) and the Emotion Regulation Questionnaire (ERQ, likert scale 1-7).
Impact of E2 concentration and emotion regulation traits on functional connectivity
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes (connectivity) during neuroimaging
Resting state functional connectivity (assessed via resting state fMRI) will be compared between E2 and placebo conditions in dependence of emotion regulation traits in ROIs (as above). Emotion regulation traits assessed via the Heidelberg Form of Emotion Regulation (HFERST, ranging from 1 to 5) and the Emotion Regulation Questionnaire (ERQ, likert scale 1-7).
Impact of E2 concentration and associated structural brain changes on connectivity
时间窗: From first measurement up to 6 months, with at least two months apart; each time before and after pill intake (6 minutes structure and 7 minutes connectivity)
In order to investigate to which degree structural changes in association with E2 concentrations are related to changes in connectivity, both structure and connectivity were assessed via anatomical (MPRAGE) and resting state MRI scans.
Impact of E2 concentration on resting state functional connectivity
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes during neuroimaging
Resting state functional connectivity (assessed via resting state fMRI) will be compared between E2 and placebo condition in the whole brain and ROIs (as above).
Impact of E2 concentration and state emotion regulation on connectivity
时间窗: From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes (connectivity) and 20 minutes (emotion regulation task)
Resting state functional connectivity (assessed via resting state fMRI) will be compared between E2 and placebo conditions in dependence of emotion regulation ratings in ROIs (as above). State emotion regulation ratings obtained via the emotion regulation task (subjective rating ranging from -200 to 200).
次要结局
- Impact of E2 concentration and self-esteem on functional connectivity(From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes during neuroimaging)
- Impact of E2 concentration and subjective mood on brain structure(From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging)
- Impact of E2 concentration and self-esteem on brain structure(From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging)
- Impact of E2 administration on E2 concentrations(From first measurement up to 6 months, with at least two months apart; each time before and after pill intake)
- Impact of E2 concentration and state anxiety on brain structure(From first measurement up to 6 months, with at least two months apart; each time: approx. 6 minutes during neuroimaging)
- Impact of E2 administration on testosterone and progesterone concentration(From first measurement up to 6 months, with at least two months apart; each time before and after pill intake)
- Impact of E2 concentration and subjective mood on functional connectivity(From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes during neuroimaging)
- Impact of E2 concentration and state anxiety on functional connectivity(From first measurement up to 6 months, with at least two months apart; each time: approx. 7 minutes during neuroimaging)
- Impact of E2 administration on E2-progesterone ratio(From first measurement up to 6 months, with at least two months apart; each time before and after pill intake)