Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001752

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Estrogen therapy has been associated with reduced risk of coronary heart disease events in observational studies of postmenopausal women. Although favorable effects of estrogen on lipoprotein cholesterol levels probably account for much of this benefit, direct vascular effects (vasomotor, hemostatic, anti-inflammatory) regulated by nitric oxide (NO) may also be of importance. We have recently shown that vasodilator effects of estrogen in the coronary circulation are due to enhanced bioactivity of NO released from the endothelium. Estrogen has been shown to stimulate synthesis and activity of the enzyme NO synthase with enhanced NO synthesis in endothelial cells in culture. Because L-arginine is the natural substrate for the enzyme NO synthase, we propose that the combination of L-arginine and estrogen might have additive vasomotor, hemostatic and anti-inflammatory effects in hypercholesterolemic postmenopausal women.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia Postmenopause	Drug: L-arginine Drug: Estrogen	Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women

Study Start Date :

Sep 1, 1998

Study Completion Date :

Jul 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

All volunteer subjects will be assessed for study participation, including a cardiovascular physical examination and resting electrocardiogram. Fasting blood will be taken for SMAC, CBC, thyroid battery, lipid levels, estradiol and FSH levels under screening protocol 94-H-0045. A urine pregnancy test will be performed in women with a uterus and cessation of menses less than 6 months. Aspirin and non-steroidal anti-inflammatory drugs and steroidal drugs (oral, ointment, drops or inhalation) will be stopped 10 days prior to starting the study and discontinued throughout the study.

Thirty hypercholesterolemic (LDL greater than 130 mg/dL) postmenopausal women who have not taken estrogenic hormone, antioxidant vitamins (A, C, E), or lipid-lowering therapy in the preceding 2 months will be selected to take part in this double-blind, cross-over study.

No subjects with plasma estradiol level greater than 50 pg/ml and FSH less than 50 pg/ml.

No subjects with blood pressure greater than 160/100 mm/Hg (off medication).

No subjects smoking cigarettes within 6 months.

No pregnant subjects.

No subjects with a history of deep venous thrombosis/pulmonary embolus.

No subjects with important chronic medical conditions (cancer, coronary artery disease, diabetes mellitus, COPD, renal disease) other than hypothyroidism if the subject is euthyroid on thyroid replacement.

No subjects who refuse to follow nitrate-restricted diet for 3 days prior to each study.