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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001752
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: August 1999
  Purpose

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 Intervention Phase
Hypercholesterolemia
Postmenopause
Drug: L-arginine
Drug: Estrogen
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Vascular and Metabolic Effects of Hormone Therapy Combined With L-Arginine in Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 30
Study Start Date: September 1998
Estimated Study Completion Date: July 2000
Detailed 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00001752

Locations
United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001752     History of Changes
Other Study ID Numbers: 980158, 98-H-0158
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Adhesion Molecules
Endothelial Function
Inflammation
Lipoproteins
Nitric Oxide
Hormone Therapy
Postmenopausal Women

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014