Hormones and Cognitive Processing in Early Postmenopausal Women
Overview
- Phase
- Not Applicable
- Intervention
- Estradiol (E2)
- Conditions
- Menopausal Syndrome
- Sponsor
- University of Michigan
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The objective of this study is to evaluate the neurobiological effects of hormone therapy (HT) in healthy early postmenopausal women. The studies proposed in this project seek to define the association between different hormone forms (estradiol only and progesterone only) versus placebo on brain functional measures. The functional measures will include the performance of the volunteers on a comprehensive neuropsychological testing battery, and the brain functional responses to episodic memory (verbal and non-verbal) challenges as well as emotional processing determined with functional magnetic resonance imaging (fMRI).
Detailed Description
Specific Aims Aim 1. To examine the effects of estradiol alone on brain functioning in early post-menopausal women during verbal and non-verbal cognitive tasks. Hypothesis: It is expected that with estradiol treatment brain activation will be more prominent in the hippocampus and prefrontal cortical areas compared to placebo. The magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall. Aim 2. To determine the effects of progesterone alone on brain functioning in early postmenopausal women during verbal and non-verbal cognitive tasks. Hypothesis: It is expected that with progesterone treatment brain activation in the hippocampus and prefrontal cortical areas will be decreased compared to both the placebo condition (within subjects) and the estradiol condition (between subjects). Interindividual variations in the magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall. Aim 3. To determine the individual effects of estradiol and progesterone on brain functioning in early postmenopausal women during emotional processing stimuli. Hypothesis: During negative stimuli estradiol-treated women compared to placebo group, are expected to have increased activity in the amygdala, posterior cingulate, and orbitofrontal cortex, while in progesterone-treated women compared to placebo, decreased activity is expected in these brain regions.
Investigators
Yolanda Smith, M.D.
Professor
University of Michigan
Eligibility Criteria
Inclusion Criteria
- •Postmenopausal women
- •Ages 45-55, 6 - 36 months from their last menstrual period.
Exclusion Criteria
- •Left handedness
- •Acute medical illness
- •Neurologic illness
- •Psychiatric illness
- •Heart disease
- •Thromboembolic disease
- •Liver disease
- •Uncorrected thyroid disease
- •Neurological disease
- •Porphyria
Arms & Interventions
Estrogen followed by Placebo
Estrogen treatment with Estradiol (E2) followed by Placebo.
Intervention: Estradiol (E2)
Estrogen followed by Placebo
Estrogen treatment with Estradiol (E2) followed by Placebo.
Intervention: Progesterone (P10) x10
Progesterone followed by Placebo
Progesterone (P10) treatment followed by Placebo.
Intervention: Progesterone (P10) x90
Placebo followed by Estrogen
Placebo followed by Estrogen treatment with Estradiol (E2)
Intervention: Estradiol (E2)
Placebo followed by Estrogen
Placebo followed by Estrogen treatment with Estradiol (E2)
Intervention: Progesterone (P10) x10
Placebo followed by Progesterone
Placebo followed by Progesterone (P10) treatment.
Intervention: Progesterone (P10) x90
Outcomes
Primary Outcomes
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Time Frame: August 2010 - March 2012
Measure the changes in brain activity in visual tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a visual working memory task, where the women are presented with 3 geometric grids on the screen. The target grid is on top, and 2 test grids are on the bottom. The women must decide if the right or left test grid matches the grid on top. There are 3 conditions: a match condition where all 3 grids are shown simultaneously, and 2 delay conditions, where the target grid is shown first, disappears, and the test grids appear after a 1 or a 4 second delay. The test was administered 3 months after baseline and 38 weeks after baseline.
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Time Frame: August 2010 - March 2012
Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing). The test was administered 3 months after baseline and 38 weeks after baseline.
Secondary Outcomes
- Neuropsychological Testing Scores - Visual Learning Retention(August 2010 - March 2012)
- Neuropsychological Testing Scores - Verbal Learning Retention(August 2010 - March 2012)