|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||||||||||||||||||||||||||||
| Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00005108 |
Purpose
This study will determine the effects of hormone replacement therapy (estrogen alone or estrogen and progesterone) on the walls of arteries in postmenopausal women. Inflammation and stiffness of artery walls are two risk factors for atherosclerosis-deposits of fatty substances (plaques) that can block the vessel, causing a heart attack or stroke. Estrogen raises the levels of certain substances in the blood that cause vessel inflammation and lowers the levels of others. This study will measure the net effects of estrogen on artery wall inflammation and stiffness.
Postmenopausal women in good health may participate in this study. Volunteers will be screened for eligibility with a complete medical history, heart examination, and blood tests. Participants will be randomly assigned to receive either: 1) hormone therapy (estradiol 2 mg daily alone for women who have had a hysterectomy or estradiol plus micronized progesterone 200 mg daily for women with an intact uterus); or 2) placebo (look-alike pills that contain no active drug). Women in both groups will take pills for 3 months, then no pills for 1 month, and then will crossover to the alternate therapy for 3 months (i.e., those in the original placebo group will take hormones, and those in the hormone group will take placebo). At the end of each 3-month treatment period, participants will undergo the following procedures to assess blood vessel inflammation and stiffness:
Information from this study will increase knowledge about the effects of estrogen on vessel wall inflammation. As such, it may be used in the future to help guide decisions about chronic hormone replacement therapy in postmenopausal women.
| Condition | Intervention | Phase |
|---|---|---|
|
Atherosclerosis Healthy Vascular Disease |
Drug: Estradiol Drug: Progesterone |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Safety/Efficacy Study |
| Official Title: | Effects of Hormone Therapy on Vascular Inflammation and Compliance |
| Estimated Enrollment: | 25 |
| Study Start Date: | April 2000 |
| Estimated Study Completion Date: | January 2002 |
Vascular inflammation plays an important role in the pathogenesis of atherosclerosis and may contribute to stiffening of arteries that increases the risk of myocardial infarction and stroke. Accordingly, therapies that reduce vascular inflammation may reduce cardiovascular risk. The effect of estrogen therapy on serum markers of inflammation in postmenopausal women is divergent: Estrogen increases the levels of C-reactive protein, interleukin-6, and matrix metalloproteinase-9 ( MMP-9), but decreases levels of the soluble cell adhesion molecules ICAM-1, VCAM-1 and E-selectin. MMP-9 is secreted by macrophages and cytokine-activated smooth muscle cells, with increased expression in the vicinity of atherosclerotic plaques. Although activation of MMP-9 by estrogen could be deleterious in women with coronary artery disease by digesting the fibrous caps of vulnerable plaques and provoking thrombosis (consistent with the Heart and Estrogen/progestin Replacement Study), activation of MMP-9 in healthy postmenopausal women may remove excess matrix proteins that contribute to arterial stiffness (reduced compliance), thus reducing cardiovascular risk (consistent with the Nurses' Health Study). Reduction of levels of cell adhesion molecules might protect against new plaque development in both groups of women. The purposes of this protocol are to determine the net effects of estrogen therapy on 1) vascular inflammation in postmenopausal women, using MRI/MRA imaging of the carotid arteries, and 2) arterial compliance, derived from carotid ultrasonography and blood pressure measurements.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Ability to comprehend or unwillingness to sign the consent form.
No use of estrogen therapy within 2 months of this study.
No history of breast cancer, uterine cancer, or estrogen-dependent tumor.
No history of deep vein thrombosis or pulmonary embolus.
No cigarette smokers (within 2 years).
No diabetes mellitus (FBS greater than 120 mg/dL).
Triglycerides less than 400 mg/dL.
Blood pressure less than 160/90 without antihypertensive therapy.
No history of coronary artery disease.
No history of carotid artery disease or stroke.
No history of pancreatitis.
No history of claustrophobia.
No history of involuntary motion disorder.
Specific MRI exclusion criteria (i.e., no pacemaker, no cochlear implants, no AICD, no internal infusion pump, no metal implants or clips in field of view).
No systemic inflammatory disorder (e.g., rheumatoid arthritis, periarteritis nodosa, systemic lupus erythromatosus, temporal arteritis).
Must not have a need for chronic aspirin or NSAID therapy.
Contacts and Locations More Information
| Study ID Numbers: | 000111, 00-H-0111 |
| Study First Received: | April 11, 2000 |
| Last Updated: | March 3, 2008 |
| ClinicalTrials.gov Identifier: | NCT00005108 |
| Health Authority: | United States: Federal Government |
|
Menopause Atherosclerosis Estrogen MRI Ultrasound |
|
Atherosclerosis Arterial Occlusive Diseases Progesterone Estradiol valerate Vascular Diseases Arteriosclerosis Healthy |
Estradiol 17 beta-cypionate Estradiol Inflammation Estradiol 3-benzoate Polyestradiol phosphate Menopause |
|
Pathologic Processes Progestins Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists |
Cardiovascular Diseases Hormones Pharmacologic Actions |
