Evaluating the Roles of Estrogen and Progesterone in Heart Metabolism

This study has been completed.
Sponsor:
Collaborators:
Robert Wood Johnson Foundation
Information provided by (Responsible Party):
Deborah Delano, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00565916
First received: November 29, 2007
Last updated: April 27, 2012
Last verified: April 2012
  Purpose

Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies have shown that the breakdown of fatty acids in cardiac muscle is important in maintaining a healthy heart, and that estrogen may enhance this process. Also, cardiovascular disease (CVD) occurs more frequently in postmenopausal women than in premenopausal women. This study will determine in postmenopausal women whether estrogen increases the heart's ability to use fats as energy and whether progesterone decreases this effect.


Condition Intervention
Postmenopause
Drug: Estrogen
Drug: Progesterone
Drug: Placebo Progesterone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Role of Estrogen/SERMS on Cardiac Fatty Acid Metabolism (Aim #1- Human Studies)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Roles of estrogen and progesterone in myocardial fatty acid utilization and oxidation in healthy postmenopausal women [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Extent to which the candidate specific estrogen receptor modulators (SERMs) tamoxifen and raloxifene increase myocardial fatty acid metabolism in ovariectomized mice and the comparison of the increase to that observed with estrogen [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]
  • Roles of the estrogen receptor isoforms alpha (α) and beta (ß) in modifying the roles of estrogen and the SERMs tamoxifen or raloxifene in heart metabolism of estrogen receptor knockout mice [ Time Frame: Measured at Year 2 ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: August 2004
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Hormone replacement therapy (HRT): estrogen plus progesterone
Drug: Estrogen
HRT with estrogen involves wearing a topical patch of 0.3 mg estradiol. The patch is to be placed on the lower abdomen and worn for 3 days. All participants will also undergo various heart metabolism tests, including a positron-emission tomographic (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).
Other Name: Estradiol
Drug: Progesterone
Progesterone therapy involves taking a daily pill of 200 mg Prometrium for the same 3 days that the estradiol is taken.
Other Name: Prometrium
Active Comparator: 2
Hormone replacement therapy (HRT): estrogen plus placebo
Drug: Estrogen
HRT with estrogen involves wearing a topical patch of 0.3 mg estradiol. The patch is to be placed on the lower abdomen and worn for 3 days. All participants will also undergo various heart metabolism tests, including a positron-emission tomographic (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).
Other Name: Estradiol
Drug: Placebo Progesterone
Placebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken.

Detailed Description:

Menopause is a natural event that generally occurs in women between the ages of 45 and 55. During menopause, the body starts producing less estrogen and progesterone until menstruation eventually stops. Estrogen and progesterone are involved in many important functions in a woman's body, and the drastic decline of these hormones in menopause leads to significant changes in the body. Along with such changes, postmenopausal women are at a higher risk than premenopausal women for certain health problems, such as CVD. Previous studies have revealed that alterations in the breakdown of fatty acids in cardiac muscle play a key role in a variety of cardiac disorders. In studies involving human skeletal muscle, estrogen has been shown to increase the breakdown of fatty acids, while progesterone lessens this effect. This study will determine in postmenopausal women whether estrogen increases the heart's ability to break down fats for energy use and whether progesterone decreases this effect. This study will also analyze ovariectomized mice to determine if the candidate specific estrogen receptor modulators (SERMs) raloxifene and tamoxifen increase the heart's ability to use fats as energy and whether the increase is similar to that seen with estrogen. Study investigators will also create estrogen receptor knock-out mice (mice with estrogen receptors removed) to further explore the roles of estrogen and SERMs in heart metabolism.

Participation in this double-blind study will last up to 1 month and will include three study visits. During Visit 1, participants will undergo three standard clinical evaluations. The first evaluation, a medical screening, will include a medical history exam and blood tests to measure estrogen and progesterone levels, liver and kidney function, cholesterol levels, and blood sugar and insulin levels. For the second evaluation, participants will undergo a body composition study to measure total body fat and muscle content using a dual-energy x-ray absorptiometry (DEXA) scan. During the third evaluation, participants will undergo an electrocardiogram (ECG) and an echocardiogram (ECHO), each performed immediately before and after walking on a treadmill. The ECG will measure electrical activity of the heart, and the ECHO will involve imaging the heart with an ultrasound.

Visits 2 and 3, occurring 3 days apart, will each include two imaging tests of the heart: a positron-emission tomographic (PET) scan and a resting ECHO. Throughout both tests an ECG and blood pressure cuff will be used to monitor heart rhythm and blood pressure, respectively. During the PET scan, participants will lie flat in an imaging machine for three 45- to 60- minute intervals. Blood will be drawn and radioactive tracers will be injected via intravenous lines placed in the arms. The ECHO test will also be done during the PET scan.

Between Visits 2 and 3, participants will be randomly assigned to one of two hormone replacement therapy (HRT) regimens: estrogen plus placebo or estrogen plus progesterone. All participants will wear a patch containing estrogen and take a pill of either placebo or progesterone for the 3 days leading up to Visit 3. All participants will be asked for permission to store a sample of their blood for up to 10 years to be used in future research studies.

  Eligibility

Ages Eligible for Study:   55 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy postmenopausal woman
  • Body mass index less than 30
  • Practices normal eating habits
  • Stops hormone replacement therapy at least 6 months prior to study entry

Exclusion Criteria:

  • Currently taking hormone replacement therapy
  • History of cardiovascular disease
  • Family history of coronary artery disease
  • Recent history of smoking, high blood pressure, or hyperlipidemia
  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: NCT00565916

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63366
Sponsors and Collaborators
Washington University School of Medicine
Robert Wood Johnson Foundation
Investigators
Principal Investigator: Pablo Soto, MD Washington University Medical School
  More Information

Publications:
Responsible Party: Deborah Delano, Research Laboratory Manager, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00565916     History of Changes
Other Study ID Numbers: 489, K23HL077179, IRB# 04-0812, RDRC# 538F, GCRC# 966
Study First Received: November 29, 2007
Last Updated: April 27, 2012
Health Authority: United States: Federal Government

Keywords provided by Washington University School of Medicine:
Post-Menopausal
PET
Estrogen
Progesterone
Heart Metabolism
Cardiovascular Disease

Additional relevant MeSH terms:
Estradiol
Estrogens
Progesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins

ClinicalTrials.gov processed this record on July 29, 2014