Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators

N Engl J Med. 1993 Apr 15;328(15):1069-75. doi: 10.1056/NEJM199304153281501.


Background: Most epidemiologic studies of cardiovascular disease in postmenopausal women suggest that estrogen-replacement therapy has a protective effect. The effects of the use of estrogen combined with progestin are less well studied.

Methods: To examine the associations of hormone-replacement therapy with concentrations of plasma lipids and hemostatic factors, fasting serum concentrations of glucose and insulin, and blood pressure, we studied 4958 postmenopausal women participating in a population-based investigation. Using cross-sectional data, we classified the women into four groups according to their use of hormone-replacement therapy: current users of estrogen alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, nonusers who had never used them.

Results: Current users had higher mean levels of high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 and high-density lipoprotein3, and apolipoprotein A-I than nonusers and lower mean levels of low-density lipoprotein cholesterol, apolipoprotein B, lipoprotein(a), fibrinogen, antithrombin III, and fasting serum glucose and insulin. However, current users of estrogen alone had higher triglyceride, factor VII, and protein C levels than either nonusers or current users of estrogen with progestin. After making certain assumptions, we estimated that the findings, if causal, would translate into a reduction of 42 percent in the risk of coronary heart disease in users of hormones as compared with nonusers. Women using estrogen with progestin would have an even greater estimated benefit.

Conclusions: A randomized trial is needed to eliminate possible selection biases in our observational study that are related to the prescription of replacement hormones. Nevertheless, hormone-replacement therapy appears to be associated with a favorable physiologic profile, which probably mediates its protective effects on cardiovascular disease. The use of estrogen combined with progestin appears to be associated with a better profile than the use of estrogen alone.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoproteins / blood
  • Blood Coagulation Factors / analysis
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol / blood
  • Cross-Sectional Studies
  • Estrogen Replacement Therapy*
  • Estrogens, Conjugated (USP) / administration & dosage
  • Female
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage
  • Menopause*
  • Middle Aged
  • Risk Factors


  • Apolipoproteins
  • Blood Coagulation Factors
  • Estrogens, Conjugated (USP)
  • Cholesterol
  • Medroxyprogesterone Acetate