Cardiovascular Diseases
Conditions
Keywords
Cardiovascular, vascular
Brief summary
This study compares the effects of two common hormone medications on the heart and blood vessels of healthy post-menopausal women over the age of 45. The study will take place over the course of about 5 months. Each subject will take two different medications over two six-week periods. They will be randomized at the beginning of the study to either estradiol+medroxyprogesterone acetate or estradiol+drospirenone for the first period, and will receive the other medication the second six-weeks of the study. At the very beginning of the study and at the end of each six-week treatment period, subjects will come to the hospital various tests including non-invasive blood vessel imaging tests, blood draws to test the levels of certain hormones in the body, an oral glucose tolerance test, a test to monitor renal blood flow, and 24-hour blood pressure monitoring. Between treatment periods, there will be a four-week medication-free washout period.
Interventions
DRUGEstradiol+MPA
1 single pill dose daily containing estradiol 1 mg + medroxyprogesterone acetate 2.5 mg
DRUGEstradiol+Drospirenone
1 single pill dose daily containing estradiol 1mg + drospirenone 0.5 mg
Sponsors
Bayer
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy female postmenopausal volunteers, as defined by absence of menses for at least 12 months and follicle stimulating hormone (FSH) 30 IU/L; 2. Age 45 to 75 years; 3. Systolic blood pressure \<140 and \>90 mmHg and diastolic blood pressure \<90 and \>60 mmHg at the screening visit; 4. No personal history of diabetes; 5. Body mass index \< 30 kg/m2; 6. No clinically significant abnormalities on screening tests (complete blood count, serum electrolytes, liver enzymes, thyroid stimulating hormone, urinalysis, and electrocardiogram).
Exclusion criteria
1. Current smoking, defined as smoking within the 12 months before the screening visit; 2. Alcohol intake \>1 beverage per night or history of alcohol abuse; 3. Current or past recreational drug use; 4. Personal history of hypertension, cardiovascular disease (coronary artery disease, congestive heart failure, valvular heart disease, stroke, transient ischemic attack, or intermittent claudication), hyperlipidemia, diabetes (defined as a fasting glucose ≥126 mg/dL), kidney disease, liver disease, venous or arterial thromboembolic disease, adrenal insufficiency, depression, or illness requiring overnight hospitalization in the past 6 months; 5. Risk factors for arterial or venous thromboembolism; 6. Personal history of breast cancer or any other type of cancer; 7. Personal history of endometrial hyperplasia, endometrial cancer, or unexplained vaginal bleeding; 8. History of cervical cancer or abnormal pap smear 9. Prescription or herbal medication use, excluding thyroid hormone supplementation; 10. Ischemic changes on resting electrocardiogram; 11. Serum creatinine ≥ 1.3 mg/dL. 12. Serum potassium level \> 5.0 mmol/L; 13. Known hypersensitivity to any of the study drugs; 14. Other active medical problems detected by examination or laboratory testing, except for treated hypothyroidism. 15. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD) | %FMD after 6 weeks of treatment | This crossover study examined the effects of E+MPA versus E+DRSP on brachial artery reactivity (BAR) assessed after six weeks of treatment. BAR is a noninvasive measure of endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. With this technique, inflation of an arm blood pressure cuff to suprasystolic blood pressure causes relative ischemia downstream to the cuff. Upon deflation, a brief state of increased blood flow occurs (reactive hyperemia), and the resulting increase in shear stress causes nitric oxide release and resulting vasodilation of the brachial artery (flow-mediated vasodilation). The flow-mediated changes in brachial artery diameter can be imaged by ultrasound and measured as an index of peripheral vasomotor function. BAR correlates with invasive assessments of coronary endothelial function as well as multiple cardiovascular risk factors. |
Countries
United States
Participant flow
Recruitment details
Postmenopausal women ages 45 and 75 were recruited 2009- 2011 via flyers, newspaper advertisements, Craigslist, RSVP for Health, and websites.
Pre-assignment details
Subjects were excluded after screening procedures due to history of hypertension, cardiovascular disease, hyperlipidemia, diabetes, liver disease, cancer, elevated creatinine/potassium levels, abnormal thyroid function, and evidence that menopause was not completed.
Participants by arm
| Arm | Count |
|---|---|
| E+MPA, Then E+DRSP Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks | 12 |
| E+DRSP, Then E+MPA Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | E+MPA, Then E+DRSP | E+DRSP, Then E+MPA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 10 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 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 | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD)
This crossover study examined the effects of E+MPA versus E+DRSP on brachial artery reactivity (BAR) assessed after six weeks of treatment. BAR is a noninvasive measure of endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. With this technique, inflation of an arm blood pressure cuff to suprasystolic blood pressure causes relative ischemia downstream to the cuff. Upon deflation, a brief state of increased blood flow occurs (reactive hyperemia), and the resulting increase in shear stress causes nitric oxide release and resulting vasodilation of the brachial artery (flow-mediated vasodilation). The flow-mediated changes in brachial artery diameter can be imaged by ultrasound and measured as an index of peripheral vasomotor function. BAR correlates with invasive assessments of coronary endothelial function as well as multiple cardiovascular risk factors.
Time frame: %FMD after 6 weeks of treatment
Population: The number of participants for analysis includes only the participants that completed a baseline assessment and at least one of the treatment arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E+MPA | Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD) | 5.49 % FMD after 6 weeks of treatment | Standard Deviation 3.32 |
| E+DRSP | Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD) | 3.39 % FMD after 6 weeks of treatment | Standard Deviation 3.18 |
p-value: 0.04Wilcoxon (Mann-Whitney)