Effects of Hormone Replacement Therapy on Inflammation and Stiffening of Artery Walls

• Status: Completed
• Trial end date: 2002-01-01
• Target enrollment: 0
• Participant gender: Female

Summary

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:

1. Blood tests - 60 cc (about 2 ounces) of blood will be drawn to measure levels of hormones, cholesterol, and substances in the blood that indicate inflammation of the vessels.

2. Ultrasonography - an ultrasound probe will be applied gently on the neck to image the right and left carotid arteries (arteries in the neck that lead to the brain). During the procedure, the heart's electrical activity will also be monitored with an electrocardiogram and a blood pressure cuff will be wrapped around the arm to obtain blood pressure measurements every 5 minutes.

3. Magnetic resonance imaging (MRI) - Images of the carotid arteries are taken while the volunteer lies on a table in a narrow cylinder containing a magnetic field. A padded sensor called an MRI coil is placed over the neck and earplugs are placed in the ears to muffle the loud noise of the machine during scanning. During the second half of the exam, gadolinium is injected through a catheter (thin, flexible tube) inserted into a vein. Gadolinium is a contrast agent that is used to brighten the scan images.

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Estradiol; Hormones; Progesterone

Criteria

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.