© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Both Raloxifene and Estrogen Reduce Major Cardiovascular Risk Factors in Healthy Postmenopausal Women
A 2-Year, Placebo-Controlled Study
From the Ageing Women Project: the Department of Endocrinology (G.W.d.V.-d.R., C.N), Research Institute for Endocrinology, Reproduction, and Metabolism, the Department of Internal Medicine (C.D.A.S.), and the Department of Obstetrics and Gynaecology (V.M., P.K.), Institute for Cardiovascular Research-Vrije Universiteit, University Hospital Vrije Universiteit, Amsterdam, The Netherlands; the Gaubius Laboratory, TNO-PG (P.M., C.K.), Leiden, The Netherlands; and Lilly Research Laboratories (F.C., S.W.), Indianapolis, Ind.
Correspondence to Coen Netelenbos, MD, PhD, Department of Endocrinology, University Hospital Vrije Universiteit, De Boelelaan 1117, Postbus 7057, 1007 MB Amsterdam, the Netherlands. E-mail C.netelen{at}azvu.nl
Abstract—Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54.8±3.5 (mean±SD) years who entered this double-blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (n=15) or 150 mg/d (n=13), placebo (n=13), or CEEs 0.625 mg/d (n=15). At baseline and after 6, 12, and 24 months of treatment, we assessed serum lipids, blood pressure, glucose metabolism, C-reactive protein, and various hemostatic parameters. Compared with placebo, both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L (all P<0.04) and lowered, at 24 months, the level of fibrinogen by 0.71 to 0.86 g/L (all P<0.05). The effects of raloxifene and CEEs did not differ significantly. In contrast to raloxifene, from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL (all P<0.02 versus both placebo and raloxifene). CEEs transiently increased C-reactive protein by 1.0 mg/L at 6 months (P<0.05 versus placebo) and prothrombin-derived fragment F1+2 by 0.79 nmol/L at 12 months (P<0.001 versus placebo). Finally, from 12 months on, CEEs increased triglycerides by 0.33 to 0.56 mmol/L (all P<0.05 versus both placebo and raloxifene). Our findings suggest that in healthy postmenopausal women, raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels. These treatments differ, however, in their effects on high density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1+2 and C-reactive protein.
Key Words: raloxifene • estrogen • lipids • coagulation • fibrinolysis
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