Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)

Cardiovascular Diseases Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000559
• Other study ID #: 103
• Status: Completed
• Phase: Phase 3
• First received: October 27, 1999
• Last updated: July 11, 2016
• Start date: March 1995
• Est. completion date: August 2001

Study information

• Verified date: May 2005
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

To determine the effects, in postmenopausal women, of hormone replacement therapy on progression/regression of coronary heart disease, as measured by quantitative angiography.

Description:

BACKGROUND:

The trial was a logical extension of preceding observational and cross-sectional studies on estrogen replacement therapy. Overall, the studies suggested a 50 percent reduction in risk of coronary heart disease in current estrogen users compared to non-users. In spite of such striking findings, most studies had been prone to a number of biases. One major criticism of observational studies had been that women receiving estrogen were generally healthier and more compliant than non-estrogen users.

There was a very large body of observational data suggesting that the use of estrogen in postmenopausal women reduced coronary heart disease mortality by approximately 45 percent. At the same time, there had been some concern that replacement therapy increased the likelihood of uterine cancer and perhaps breast cancer as well, although it was generally accepted that this risk was probably significantly less than the benefits obtained from the reduction of coronary heart disease mortality.

DESIGN NARRATIVE:

Randomized, double-blind, placebo-controlled. After baseline angiograms, patients were randomized to one of three arms: micronized 17-beta estradiol, 1 milligram per day; 17-beta estradiol plus medroxyprogesterone, 5 milligrams per day for twelve days per month; and placebo. Subjects in all three arms received lipid-lowering therapy, low fat/low cholesterol diet, and the HMG-CoA reductase inhibitor, pravastatin, in sufficient dosage to reduce low density lipoprotein (LDL) cholesterol levels below 130 mg/dl. The primary endpoint was progression/regression of coronary obstructive disease as measured by angiography, including the expert human panel and quantitative computer analysis. The secondary endpoint was carotid media-intima thickness determined by ultrasound. Clinical measures included lipids, lipoproteins, apolipoproteins, estradiol and medroxyprogesterone levels, urinary prostanoid metabolites, and insulin/glucose metabolism. Subjects were recruited at three centers with active coronary angiography units. Several core facilities supported the study: a Core Lipid Lab, a Reproductive Endocrine Lab, the Biostatistics Lab (Data Coordinating Center) and the Angiographic Imaging Laboratory.

The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: August 2001
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 75 Years

Eligibility

Postmenopausal women with angiographically-documented coronary disease. Approximately 70 percent minority

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Ischemia
• Myocardial Ischemia
• Postmenopause

Intervention

Drug:
• estrogen replacement therapy

• hormone replacement therapy

• estradiol

• medroxyprogesterone

Locations

Country	Name	City	State
n/a

Sponsors (1)

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

References & Publications (3)

Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL, Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M, Vogelbach KH, Selzer RH; Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003 Aug 7;349(6):535-45. — View Citation

Slater CC, Zhang C, Hodis HN, Mack WJ, Boostanfar R, Shoupe D, Paulson RJ, Stanczyk FZ. Comparison of estrogen and androgen levels after oral estrogen replacement therapy. J Reprod Med. 2001 Dec;46(12):1052-6. — View Citation

Wilcox JG, Hwang J, Hodis HN, Sevanian A, Stanczyk FZ, Lobo RA. Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein. Fertil Steril. 1997 Jan;67(1):57-62. — View Citation