Cognitive Impairment, Endothelial Dysfunction, Estrogen Deficiency, Menopause, Vascular Stiffness
Conditions
Keywords
cognitive impairment, menopause, estrogen, functional MRI, executive function, endothelial function, arterial stiffness
Brief summary
Complaints about memory and thinking are common in women as they go through menopause. The female hormone estrogen is important for both the health of both the brain and the blood vessels. In Alzheimer's disease there is damage to the blood vessels in the brain. This study will look at how the loss of the female hormone estrogen affects brain function and the health of blood vessels.
Interventions
OTHERGnRHant + E2
GnRH antagonist with estradiol add-back
OTHERGnRHant + Placebo
GnRH antagonist with placebo add-back
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Stages of Reproductive Aging Workshop (STRAW+10) peak or late reproductive stage (-4, -3b or -3a) * Healthy based on medical history, physical examination and standard blood chemistries * Normotensive (resting blood pressure \<140/90 mmHg) * Normoglycemia (fasting glucose \<110mg/dl and hemoglobin A1c\<6.5%) * Non-smoker (for at least 12 months)
Exclusion criteria
* Serum Follical Stimulating Hormone (FSH) \>25mIU/mL measured during the first 5 days of the menstrual cycle * Use of hormonal therapy within the past 3 months * Use of antihypertensive or lipid-lowering medications * Pregnant or lactating, or planning to become pregnant during the study period * Known hypersensitivity to any of the study medications * Abnormal vaginal bleeding * History of venous thromboembolism or hormone-sensitive cancer * History of neurologic disease or major psychiatric illness * History of diagnosed learning disability or less than high-school education * Contraindication to Magnetic Resonance Imaging (MRI) scanning * Depression (Center for Epidemiological Studies - Depression (CESD) score \>16) * Significant cognitive impairment (Mini Mental State Examination (MMSE) score \<27) * Severe osteopenia or osteoporosis (proximal femur or lumbar spine T-score \< -2.0) * Body Mass Index (BMI) \>40kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Prefrontal cortex brain activation | Baseline, 3 months | Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline and 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Endothelial function | Baseline, 3 months | Endothelial function will be measured using brachial artery flow-mediated dilation at baseline and 3 months |
| Changes in Arterial stiffness | Baseline, 3 months | Carotid artery compliance will be measured using ultrasound at baseline and 3 months |
| Changes in Executive cognitive function | Baseline, 3 months | Changes in executive cognitive function on a battery of neuropsychological tests will be measured at baseline and 3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Mitochondrial dysfunction | Baseline and 3 months | Measures of mitochondrial function including dynamics (fusion, fission), antioxidant defense and biogenesis will be measured in mitochondria isolated from peripheral blood mononuclear cells at baseline and 3 months. |
Countries
United States
Outcome results
None listed