Clinical trial NCT01268046: Aging and Estrogen on Cortical Function
Official title: The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Memory Loss
Cognitive Changes
Postmenopausal Symptoms
Keywords: aging
postmenopausal women
estrogen
memory
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2010-12-29
Enrollment: 38
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant was randomized to placebo or estrogen using a block randomized design by age group
Primary purpose: OTHER

Brief summary: This study will focus on how estrogen affects parts of the brain associated with memory and how the effect of estrogen is altered with aging in postmenopausal women.

Detailed description: The broad goal of this proposal is to determine the effect of aging on areas of the brain whose function is impacted by gonadal steroids in women. The overarching hypothesis is that aging differentially alters the effects of estrogen on the brain. Our preliminary data indicated that aging alters the effect of estrogen on brain regions involved in cognition and thus, the current study focused on the impact of aging on functional changes induced by estrogen in cortical and subcortical areas associated with verbal working memory and declarative/episodic memory.

As our model, we will use women in whom the absence of gonadal function makes it possible to control the duration and amount of estrogen exposure, specifically postmenopausal women who are younger (45-55) or older (65-80) who receive either oral or transdermal estradiol to achieve premenopausal early follicular phase estradiol levels.. We evaluate the effects of low dose estrogen exposure at 48 hr and 1 month to determine whether the short-term changes in brain regions involved in cognition with low dose estrogen exposure seen in our preliminary studies are confirmed and whether changes with short-term estrogen exposure persist with more prolonged exposure, a finding that would have enormous clinical relevance. These studies, using sophisticated neuroimaging tools (structural and functional magnetic resonance imaging \[MRI\] and \[18F\] 2-fluoro-2-deoxy-D-glucose positron emission tomography \[FDG-PET\]), provide a unique window into the brain in women.

Eligibility criteria: Inclusion Criteria:

1. young postmenopausal (age 45-55) or older (age 65-80) postmenopausal women
2. otherwise healthy, non-obese women with normal blood pressure and a history of normal menopause, defined by the absence of menses for at least 12 months
3. prescription hormone replacement treatment discontinued at least 3 months before study
4. Normal or corrected normal vision
5. Intelligence quotient (IQ) \> 70 on the Wechsler Adult Reading Test (WTAR)\*
6. Absence of Mild Cognitive Impairment (MCI) and depression on the Mini Mental State Examination (MMSE)\*\* and Beck Depression Inventory II (BDI-II).\*\*\*
7. Normal mammogram or breast MRI within the past 2 years

Exclusion Criteria

1. On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment within three months of study
2. History of radiotherapy or chemotherapy.
3. Absolute contraindications to the use of physiologic replacement doses of estrogen and/or history of coronary artery disease
4. History of breast cancer, blood clot, pulmonary embolus, hypercoagulability and stroke.
5. On centrally acting medications
6. History of head trauma and/or neurologic disorder
7. Contraindication to MRI (eg. metal implants) or PET imaging (eg. PET imaging studies in the previous 12 months)
8. Concurrent participation in research studies involving medications and/or PET scans.
9. Left handedness.
10. Current breast lump(s) or family/genetic history of breast cancer in younger women (\< 40 years old).
11. Current smoking

Primary outcomes:
measure: Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)
timeFrame: baseline to 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Reproductive Endocrine Unit, Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Janet E Hall, MD
role: PRINCIPAL_INVESTIGATOR
References: