Effects of Aging and Estrogen on Memory and Cognition

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01268046
First received: December 28, 2010
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

This study will focus on how aging affects changes in the way the brain works when affected by estrogen in areas of the brain associated with memory.


Condition Intervention
Memory Loss
Cognitive Changes
Postmenopausal Symptoms
Drug: Estradiol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Aging and Estrogen on Cortical Function

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Neuroimaging changes in response to estrogen [ Time Frame: 48 hrs and 28-30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neuropsychological testing changes in response to receiving estradiol [ Time Frame: 48 hrs and 28-30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: November 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Postmenopausal women 45-55 years old Drug: Estradiol
1mg/day for 30 days administered through a capsule
Other Name: Micronized Estradiol from Mylan Pharmaceuticals
Postmenopausal women 65-80 years old Drug: Estradiol
1mg/day for 30 days administered through a capsule
Other Name: Micronized Estradiol from Mylan Pharmaceuticals
Women with Premature Ovarian Insufficiency (POI) < 45 yrs Drug: Estradiol
1mg/day for 30 days administered through a capsule
Other Name: Micronized Estradiol from Mylan Pharmaceuticals

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 indicate that aging alters the effect of estrogen on brain regions involved in cognition and thus, the current proposal will focus 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 young women with Premature Ovarian Insufficiency (POI) < 45 yrs. old (but diagnosed at < 40 yrs.) and postmenopausal women who are younger (45-55) or older (65-80). We will investigate the effects of both short-term (48 hr) and prolonged (28-30 days) estrogen exposure to determine whether the changes in brain regions involved in cognition that were seen with short-term estrogen exposure persist with 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 the human.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  1. Three groups of menopausal women will be recruited for these studies:

    • young (age 45-55)
    • older (age65-80) postmenopausal women (PMW)
    • women with Premature Ovarian Insufficiency (POI) < 45 yrs. old (but diagnosed at < 40 yrs.)
  2. The subjects will be otherwise healthy, non-obese women, normotensive and non-smokers
  3. History of normal menopause, defined by the absence of menses for at least 12 months
  4. Subjects with premature menopause will have had:

    • menarche between the ages of 10 and 15
    • regular menstrual cycles before the onset of ovarian failure at < 35
    • at least 1 year of amenorrhea before study or no unscheduled menses while on HRT (discontinued at least 3 months before study, as above)
    • have normal adrenal function and not be carriers for the Fragile X premutation
  5. FSH > 26 IU/L (2nd IRP HMG) and E2 < 25 pg/mL at screening and on the initial day of study and normal TSH, and Factor V activity
  6. Normal or corrected normal vision
  7. IQ > 70 on the Wechsler Adult Reading Test (WTAR)*
  8. Absence of Mild Cognitive Impairment (MCI) and depression on the Mini Mental State Examination (MMSE)** and Beck Depression Inventory II (BDI-II).***
  9. Normal mammogram or breast MRI within the past 2 years (age 45 and older only).

Exclusion Criteria

  1. On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment for 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268046

Contacts
Contact: Taylor A Huhta, BA 617-726-5384 thuhta@partners.org

Locations
United States, Massachusetts
Reproductive Endocrine Unit, Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Janet E Hall, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01268046     History of Changes
Other Study ID Numbers: 2009P-002311, R01AG013241
Study First Received: December 28, 2010
Last Updated: July 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
aging
postmenopausal women
estrogen
memory

Additional relevant MeSH terms:
Memory Disorders
Amnesia
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on August 25, 2014