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

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001752
• Other study ID #: 980158
• Secondary ID: 98-H-0158
• Status: Completed
• Phase: Phase 2
• First received: November 3, 1999
• Last updated: March 3, 2008
• Start date: September 1998
• Est. completion date: July 2000

Study information

• Verified date: August 1999
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2000
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Postmenopause

Intervention

Drug:
• L-arginine

• Estrogen

Locations

Country	Name	City	State
United States	National Heart, Lung and Blood Institute (NHLBI)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Guetta V, Quyyumi AA, Prasad A, Panza JA, Waclawiw M, Cannon RO 3rd. The role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women. Circulation. 1997 Nov 4;96(9):2795-801. — View Citation

Hayashi T, Fukuto JM, Ignarro LJ, Chaudhuri G. Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11259-63. — View Citation