Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Endothelial Dysfunction; Cognitive Impairment; Executive Dysfunction; Cardiovascular Disease

Treatments: Drug: Leuprolide acetate; Drug: Medroxyprogesterone; Drug: Placebo; Drug: Estradiol

Study type: Interventional

Funder types: Other

Identifiers

NCT02122198

14-0193

UL1TR001082 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Complaints about memory and thinking are common in women as they go through menopause and estrogen levels fall. The ovarian hormone estrogen is important for supporting normal cognitive function, and changes in brain activity and function occur when estrogen levels are decreased. Estrogen is also important for maintaining healthy blood vessels which also support normal cognitive function. In Alzheimer's disease and other types of dementia, there is significant damage to the blood vessels in the brain. This study will test whether changes in brain activity and function with the loss of estrogen are related to changes in vascular function. The investigators will measure vascular function using ultrasound, and brain activity using MRI scans in women who are enrolled in the Females, Aging, Metabolism and Exercise (FAME) study (NCT01712230). In the FAME study, healthy premenopausal women either take a medication to decrease their estrogen levels, or a placebo. This sub-study may provide new information about how estrogen affects vascular function and cognitive function, and lead to new ways to prevent or delay cognitive impairment or dementia.

Enrollment: 17 patients

Sex: Female

Ages: 40 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Volunteers will be healthy women aged 40 to 60 years
2. Are enrolled in the parent FAME study (NCT01712230).

The Investigators will consent up to 80 subjects with the aim of enrolling 17 in each of the 2 groups (placebo, GnRH agonist).

Exclusion criteria

1. mini-mental state examination (MMSE) score 27 or less
2. history of neurologic disease or major psychiatric illness
3. major depressive episode within the past 12 months
4. history of learning disability
5. less than high-school education
6. current smoking
7. use of psychoactive medications in the past 3 months (stable use of anti- depressant medication is allowed)
8. contraindications to MRI scanning

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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17 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230)

Treatment:

Drug: Placebo

GnRH agonist

Active Comparator group

Description:

Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30.

Treatment:

Drug: Estradiol

Drug: Medroxyprogesterone

Drug: Leuprolide acetate