Effects of Ovarian Hormone Suppression on Vascular and Cognitive Function

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Menopause; Endothelial Dysfunction; Vascular Stiffness; Estrogen Deficiency
• Intervention / Treatment: Other: GnRHant + E2; Other: GnRHant + Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
    • Boulder, Colorado, United States, 80309
      • University of Colorado Boulder Intermountain Neuroimaging Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Mitochondrial dysfunction	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.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Kerry L Hildreth, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Actual): June 6, 2020
• Study Completion (Actual): June 21, 2020

Study Registration Dates

• First Submitted: April 7, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (Actual): April 13, 2017

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: menopause; estrogen; functional MRI; executive function; endothelial function; arterial stiffness; cognitive impairment
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Hormone Antagonists; Estradiol; LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-
• Other Study ID Numbers: 17-0092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No