Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

Conditions
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Vascular Stiffness, Cognitive Impairment, Menopause, Estrogen Deficiency, Endothelial Dysfunction

Intervention / Treatment
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* Other: GnRHant + E2
* Other: GnRHant + Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GnRHant + E2<br>Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal estradiol add-back; Climara patch, 0.075mg/day, weekly for 12 weeks | Other: GnRHant + E2<br>* GnRH antagonist with estradiol add-back<br>* Other names: Degarelix acetate, Firmagon + Estradiol, Climara transdermal system;|
| Placebo Comparator: GnRHant + Placebo<br>Single dose of GnRH antagonist degarelix acetate for depot injection (80mg) Transdermal placebo patch, weekly for 12 weeks | Other: GnRHant + Placebo<br>* GnRH antagonist with placebo add-back<br>* Other names: Degarelix acetate, Firmagon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Prefrontal cortex brain activation | 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 | Baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Endothelial function | Endothelial function will be measured using brachial artery flow-mediated dilation at baseline and 3 months | Baseline, 3 months | 
| Changes in Arterial stiffness | Carotid artery compliance will be measured using ultrasound at baseline and 3 months | Baseline, 3 months | 
| Changes in Executive cognitive function | Changes in executive cognitive function on a battery of neuropsychological tests will be measured at baseline and 3 months | Baseline, 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arterial stiffness, cognitive impairment, menopause, estrogen, functional MRI, executive function, endothelial function