Clinical trial NCT00000559: Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Coronary Disease
Heart Diseases
Myocardial Ischemia
Postmenopause
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

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

Detailed 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).

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Southern California
name: Howard Hodis
References:
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.
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. doi: 10.1016/s0015-0282(97)81856-0.
citation: 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. doi: 10.1056/NEJMoa030830.
citation: Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, Hodis HN. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7. doi: 10.1097/01.AOG.0000251518.56369.eb.