Postmenopausal Syndrome
Conditions
Keywords
Post-Menopausal, PET, Estrogen, Progesterone, Heart Metabolism, Cardiovascular Disease
Brief summary
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.
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.
Interventions
DRUGEstrogen
Estrogen only plus placebo: estradiol topical patch 0.3 mg placed on the lower abdomen for 3 days plus an oral placebo. Other procedures: heart metabolism tests which includes a positron-emission tomography (PET) scan, an electrocardiogram (ECG), and an echocardiogram (ECHO).
DRUGProgesterone
Estrogen plus progesterone: estradiol with oral progesterone (Prometrium, 200 mg/day) for 3 days, instead of placebo. Progesterone therapy involves taking a daily oral pill of 200 mg Prometrium for the same 3 days that the estradiol is taken.
DRUGPlacebo
Placebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Robert Wood Johnson Foundation
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization. | 3 days | Measurements of myocardial fatty acid utilization and oxidation with C\[11\]-Palmitate and PET in healthy postmenopausal women who take either estrogen alone or with progesterone. The primary outcome measure was designed to determine prospectively whether estrogen will increase the heart's fatty acid utilization and whether progestins will attenuate this effect, in a manner similar to what was seen in an observational study of hormone replacement therapy (HRT) in post-menopausal women. To this end, we had anticipated enrolling 30 healthy post-menopausal women for assessment of cardiac fatty acid metabolism using positron emission tomography (PET) and radioactive C\[11\]-Palmitate both before and after 3 days of hormone replacement therapy. These volunteers were to be randomized to receive either estrogen alone (E) or combined estrogen/progesterone (EP). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estrogen Plus Progesterone Hormone replacement therapy (HRT): estrogen plus progesterone
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).
Progesterone: Progesterone therapy involves taking a daily pill of 200 mg Prometrium for the same 3 days that the estradiol is taken. | 11 |
| Estrogen Plus Placebo Hormone replacement therapy (HRT): estrogen plus placebo
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).
Placebo Progesterone: Placebo progesterone therapy involves taking a daily placebo pill for the same 3 days that the estradiol is taken. | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Estrogen Plus Progesterone | Estrogen Plus Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization.
Measurements of myocardial fatty acid utilization and oxidation with C\[11\]-Palmitate and PET in healthy postmenopausal women who take either estrogen alone or with progesterone. The primary outcome measure was designed to determine prospectively whether estrogen will increase the heart's fatty acid utilization and whether progestins will attenuate this effect, in a manner similar to what was seen in an observational study of hormone replacement therapy (HRT) in post-menopausal women. To this end, we had anticipated enrolling 30 healthy post-menopausal women for assessment of cardiac fatty acid metabolism using positron emission tomography (PET) and radioactive C\[11\]-Palmitate both before and after 3 days of hormone replacement therapy. These volunteers were to be randomized to receive either estrogen alone (E) or combined estrogen/progesterone (EP).
Time frame: 3 days
Population: 22 healthy post'menopausal women. These volunteers were to be randomized to receive either estrogen alone, or combined estrogen/progesterone. Efforts were made to access the data, PI left institution and there is no access to the data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Estrogen Plus Progesterone | Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization. | NA Participants |
| Estrogen Plus Placebo | Number of Participants That Had an Increase in Myocardial Fatty Acid Utilization. | NA Participants |