Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women

Abstract

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 estroge n alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, and nonusers who had never used them. Results: Current users had higher mean levels of high-density lipoprotein cholesterol, its subfractions high-density lipoprotein 2 and high-density lipoprotein 3 , 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., In 1985, about 3 million postmenopausal women in the United States were using hormone-replacement therapy to alleviate symptoms associated with menopause 1 . More than 20 studies have been conducted to assess the effects of this therapy on coronary heart disease 2 . The majority of those studies, particularly the prospective studies, revealed a protective effect of the use of estrogen-replacement therapy 2 . Hormone-replacement therapy may modify the risk of coronary heart disease by several mechanisms; possibilities include alterations in plasma concentrations of lipoproteins, 3 hemostatic factors, 3 , 4 glucose, and insulin 4 and of blood pressure 5 . Epidemiologic studies of the physiologic effects of… © 1993, Massachusetts Medical Society. All rights reserved.