Women's Estrogen/Progestin Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia; Postmenopause
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Ischemia
Study type: Interventional
Phase: Phase 3

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).
    

Intervention name(s): estrogen replacement therapy; hormone replacement therapy; estradiol; medroxyprogesterone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Medroxyprogesterone Acetate; Medroxyprogesterone; Hormones; Estradiol; Estrogens
Allocation: Randomized
Masking: Double
Primary purpose: Prevention