This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (438)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Women's Health  • Menopause  • Alert me on articles by topic  Social Bookmarking   What's this?

Brian W. Walsh, MD; Lewis H. Kuller, MD; Robert A. Wild, MD; Sofia Paul, PhD; Mildred Farmer, MD; Jeffry B. Lawrence, MD; Aarti S. Shah, PhD; Pamela W. Anderson, MD

JAMA. 1998;279:1445-1451.

Context.— Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.

Objective.— To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT).

Design.— Double-blind, randomized, parallel trial.

Setting.— Eight sites in the United States.

Participants.— 390 healthy postmenopausal women recruited by advertisement.

Intervention.— Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo.

Main Outcome Measures.— Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment.

Results.— At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P<.001), similar to the 14% reduction with HRT (P<.001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P<.001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL₂-C) by 15% to 17% (P<.05), less than the 33% increase with HRT (P<.001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P< .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P<.001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2.

Conclusions.— Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL₂-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL₂-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.

From the Brigham and Women's Hospital, Boston, Mass (Dr Walsh); University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); University of Oklahoma Health Sciences Center, Oklahoma City (Dr Wild); Lilly Research Laboratories, Indianapolis, Ind (Drs Paul, Lawrence, Shah, and Anderson); and Clinical Studies, St Petersburg, Fla (Dr Farmer).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLE

Of Designer Drugs, Magic Bullets, and Gold Standards
Basil M. Rifkind and Jacques E. Rossouw
JAMA. 1998;279(18):1483-1485.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Effects of the Selective Estrogen Receptor Modulator Raloxifene on Coronary Outcomes in The Raloxifene Use for the Heart Trial: Results of Subgroup Analyses by Age and Other Factors
Collins et al.
Circulation 2009;119:922-930.
ABSTRACT | FULL TEXT  

Review Article: A New Approach to Menopausal Therapy: The Tissue Selective Estrogen Complex
Komm
Reproductive Sciences 2008;15:984-992.
ABSTRACT  

The Rise of Raloxifene and the Fall of Invasive Breast Cancer
Jordan
JNCI J Natl Cancer Inst 2008;100:831-833.
FULL TEXT  

Toremifene Improves Lipid Profiles in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer: Interim Analysis of a Multicenter Phase III Study
Smith et al.
JCO 2008;26:1824-1829.
ABSTRACT | FULL TEXT  

SERMs: Meeting the Promise of Multifunctional Medicines
Jordan
JNCI J Natl Cancer Inst 2007;99:350-356.
ABSTRACT | FULL TEXT  

Raloxifene Increases Proliferation and Up-regulates Telomerase Activity in Human Umbilical Vein Endothelial Cells
Doshida et al.
J. Biol. Chem. 2006;281:24270-24278.
ABSTRACT | FULL TEXT  

Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.
Barrett-Connor et al.
NEJM 2006;355:125-137.
ABSTRACT | FULL TEXT  

Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial
Vogel et al.
JAMA 2006;295:2727-2741.
ABSTRACT | FULL TEXT  

Progression of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in Relation to Incident Type 2 Diabetes
Festa et al.
Circulation 2006;113:1753-1759.
ABSTRACT | FULL TEXT  

Effect of Raloxifene on Serum Triglycerides in Women With a History of Hypertriglyceridemia While on Oral Estrogen Therapy
Carr et al.
Diabetes Care 2005;28:1555-1561.
ABSTRACT | FULL TEXT  

Raloxifene relaxes rat intrarenal arteries by inhibiting Ca2+ influx
Leung et al.
Am. J. Physiol. Renal Physiol. 2005;289:F137-F144.
ABSTRACT | FULL TEXT  

Selective Estrogen-Receptor Modulators for Primary Prevention of Breast Cancer
Fabian and Kimler
JCO 2005;23:1644-1655.
FULL TEXT  

The Effects of Tamoxifen and Its Metabolites on Platelet Function and Release of Reactive Oxygen Intermediates
Vitseva et al.
J. Pharmacol. Exp. Ther. 2005;312:1144-1150.
ABSTRACT | FULL TEXT  

Estrogen Regulation of Growth Hormone Action
Leung et al.
Endocr. Rev. 2004;25:693-721.
ABSTRACT | FULL TEXT  

The Consequences of Exhaustive Antiestrogen Therapy in Breast Cancer: Estrogen-Induced Tumor Cell Death
Osipo et al.
Exp. Biol. Med. 2004;229:722-731.
ABSTRACT | FULL TEXT  

Raloxifene Relaxes Rat Cerebral Arteries In Vitro and Inhibits L-Type Voltage-Sensitive Ca2+ Channels
Tsang et al.
Stroke 2004;35:1709-1714.
ABSTRACT | FULL TEXT  

Tamoxifen and ICI 182,780 negatively influenced cardiac cell growth via an estrogen receptor-independent mechanism
Mercier et al.
Cardiovasc Res 2003;59:883-892.
ABSTRACT | FULL TEXT  

Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease
Griffiths et al.
J Am Coll Cardiol 2003;42:698-704.
ABSTRACT | FULL TEXT  

Fibrinogen - marker or mediator of vascular disease?
Reinhart
Vasc Med 2003;8:211-216.
ABSTRACT  

Efficacy and Safety of Raloxifene 60 Milligrams/Day in Postmenopausal Asian Women
Kung et al.
J. Clin. Endocrinol. Metab. 2003;88:3130-3136.
ABSTRACT | FULL TEXT  

New Markers for Cardiovascular Disease Risk in Women: Impact of Endogenous Estrogen Status and Exogenous Postmenopausal Hormone Therapy
Davison and Davis
J. Clin. Endocrinol. Metab. 2003;88:2470-2478.
ABSTRACT | FULL TEXT  

Endothelial Function and Menopause: Effects of Raloxifene Administration
Colacurci et al.
J. Clin. Endocrinol. Metab. 2003;88:2135-2140.
ABSTRACT | FULL TEXT  

Estrogen and Cognitive Functioning in Women
Sherwin
Endocr. Rev. 2003;24:133-151.
ABSTRACT | FULL TEXT  

Lignes directrices de pratique clinique 2002 pour le diagnostic et le traitement de l'osteoporose au Canada
Brown and Josse
CMAJ 2003;168:SF1-38.
ABSTRACT | FULL TEXT  

Selective Estrogen-Receptor Modulators -- Mechanisms of Action and Application to Clinical Practice
Riggs and Hartmann
NEJM 2003;348:618-629.
FULL TEXT  

Hormone Replacement Therapy and Risk of Cardiovascular Disease: Implications of the Results of the Women's Health Initiative
Kuller
Arterioscler. Thromb. Vasc. Bio. 2003;23:11-16.
ABSTRACT | FULL TEXT  

Influence of Tamoxifen on Carotid Intima-Media Thickness in Postmenopausal Women
Simon et al.
Circulation 2002;106:2925-2929.
ABSTRACT | FULL TEXT  

Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial
Palomba et al.
Hum Reprod 2002;17:3213-3219.
ABSTRACT | FULL TEXT  

2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada
Brown and Josse
CMAJ 2002;167:s1-34.
ABSTRACT | FULL TEXT  

Raloxifene Administration in Women Treated with Gonadotropin-Releasing Hormone Agonist for Uterine Leiomyomas: Effects on Bone Metabolism
Palomba et al.
J. Clin. Endocrinol. Metab. 2002;87:4476-4481.
ABSTRACT | FULL TEXT  

Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart
Ogita et al.
J Am Coll Cardiol 2002;40:998-1005.
ABSTRACT | FULL TEXT  

Raloxifene Does Not Modify Insulin Sensitivity and Glucose Metabolism in Postmenopausal Women
Cagnacci et al.
J. Clin. Endocrinol. Metab. 2002;87:4117-4121.
ABSTRACT | FULL TEXT  

The Effect of Raloxifene on Glyco-Insulinemic Homeostasis in Healthy Postmenopausal Women: A Randomized Placebo-Controlled Study
Cucinelli et al.
J. Clin. Endocrinol. Metab. 2002;87:4186-4192.
ABSTRACT | FULL TEXT  

IV. Meta-Analysis of Raloxifene for the Prevention and Treatment of Postmenopausal Osteoporosis
Cranney et al.
Endocr. Rev. 2002;23:524-528.
FULL TEXT  

Raloxifene Administration in Premenopausal Women with Uterine Leiomyomas: A Pilot Study
Palomba et al.
J. Clin. Endocrinol. Metab. 2002;87:3603-3608.
ABSTRACT | FULL TEXT  

Chemoprevention of Breast Cancer: A Summary of the Evidence for the U.S. Preventive Services Task Force
Kinsinger et al.
ANN INTERN MED 2002;137:59-69.
ABSTRACT | FULL TEXT  

Nongenomic Mechanisms of Endothelial Nitric Oxide Synthase Activation by the Selective Estrogen Receptor Modulator Raloxifene
Simoncini et al.
Circulation 2002;105:1368-1373.
ABSTRACT | FULL TEXT  

Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis
Johnell et al.
J. Clin. Endocrinol. Metab. 2002;87:985-992.
ABSTRACT | FULL TEXT  

Inhibition of Intimal Hyperplasia Using the Selective Estrogen Receptor Modulator Raloxifene
Selzman et al.
Arch Surg 2002;137:333-336.
ABSTRACT | FULL TEXT  

Raloxifene and Cardiovascular Events in Osteoporotic Postmenopausal Women: Four-Year Results From the MORE (Multiple Outcomes of Raloxifene Evaluation) Randomized Trial
Barrett-Connor et al.
JAMA 2002;287:847-857.
ABSTRACT | FULL TEXT  

Risk factors for coronary heart disease: implications of gender
Roeters van Lennep et al.
Cardiovasc Res 2002;53:538-549.
ABSTRACT | FULL TEXT  

Estrogen replacement therapy, atherosclerosis, and vascular function
Mikkola and Clarkson
Cardiovasc Res 2002;53:605-619.
ABSTRACT | FULL TEXT  

Antiresorptive Treatment of Postmenopausal Osteoporosis: Comparison of Study Designs and Outcomes in Large Clinical Trials with Fracture as an Endpoint
Marcus et al.
Endocr. Rev. 2002;23:16-37.
ABSTRACT | FULL TEXT  

Alcohol-Extracted, but Not Intact, Dietary Soy Protein Lowers Lipoprotein(a) Markedly
Meinertz et al.
Arterioscler. Thromb. Vasc. Bio. 2002;22:312-316.
ABSTRACT | FULL TEXT  

Raloxifene Does Not Affect Insulin Sensitivity or Glycemic Control in Postmenopausal Women with Type 2 Diabetes Mellitus: A Randomized Clinical Trial
Andersson et al.
J. Clin. Endocrinol. Metab. 2002;87:122-128.
ABSTRACT | FULL TEXT  

Induction of Endothelial Nitric-oxide Synthase Phosphorylation by the Raloxifene Analog LY117018 Is Differentially Mediated by Akt and Extracellular Signal-regulated Protein Kinase in Vascular Endothelial Cells
Hisamoto et al.
J. Biol. Chem. 2001;276:47642-47649.
ABSTRACT | FULL TEXT  

Selective Estrogen Receptor Modulation and Reduction in Risk of Breast Cancer, Osteoporosis, and Coronary Heart Disease
Jordan et al.
JNCI J Natl Cancer Inst 2001;93:1449-1457.
ABSTRACT | FULL TEXT  

Prospective Randomized Study of Effects of Unopposed Estrogen Replacement Therapy on Markers of Coagulation and Inflammation in Postmenopausal Women
Luyer et al.
J. Clin. Endocrinol. Metab. 2001;86:3629-3634.
ABSTRACT | FULL TEXT  

Selective Estrogen Receptor Modulation: A Personal Perspective
Jordan
Cancer Res. 2001;61:5683-5687.
FULL TEXT  

Hormone Replacement in Women with a History of Breast Cancer
Pritchard
The Oncologist 2001;6:353-362.
ABSTRACT | FULL TEXT  

Indicators of Lifetime Estrogen Exposure: Effect on Breast Cancer Incidence and Interaction With Raloxifene Therapy in the Multiple Outcomes of Raloxifene Evaluation Study Participants
Lippman et al.
JCO 2001;19:3111-3116.
ABSTRACT | FULL TEXT  

Hormone replacement therapy and blood pressure in normotensive and hypertensive women
Sharma et al.
Nephrol Dial Transplant 2001;16:888-890.
FULL TEXT  

The menopause and its treatment in perspective
Al-Azzawi
Postgrad. Med. J. 2001;77:292-304.
FULL TEXT  

Cognitive Function in Postmenopausal Women Treated with Raloxifene
Yaffe et al.
NEJM 2001;344:1207-1213.
ABSTRACT | FULL TEXT  

Tamoxifen Effects on Endothelial Function and Cardiovascular Risk Factors in Men With Advanced Atherosclerosis
Clarke et al.
Circulation 2001;103:1497-1502.
ABSTRACT | FULL TEXT  

Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance
Clarke et al.
Pharmacol. Rev. 2001;53:25-72.
ABSTRACT | FULL TEXT  

Tamoxifen and Cardiac Risk Factors in Healthy Women : Suggestion of an Anti-inflammatory Effect
Cushman et al.
Arterioscler. Thromb. Vasc. Bio. 2001;21:255-261.
ABSTRACT | FULL TEXT  

Estrogen, Selective Estrogen Receptor Modulation, and Coronary Heart Disease: Something or Nothing
Jordan
JNCI J Natl Cancer Inst 2001;93:2-4.
FULL TEXT  

Long-term Effects of Raloxifene on Bone Mineral Density, Bone Turnover, and Serum Lipid Levels in Early Postmenopausal Women: Three-Year Data From 2 Double-blind, Randomized, Placebo-Controlled Trials
Johnston et al.
Arch Intern Med 2000;160:3444-3450.
ABSTRACT | FULL TEXT  

Effects of Continuous Estrogen and Estrogen-Progestin Replacement Regimens on Cardiovascular Risk Markers in Postmenopausal Women
Davidson et al.
Arch Intern Med 2000;160:3315-3325.
ABSTRACT | FULL TEXT  

Effects of hormonal replacement therapy on lipid and haemostatic factors in post-menopausal ESRD patients
Park et al.
Nephrol Dial Transplant 2000;15:1835-1840.
ABSTRACT | FULL TEXT  

Raloxifene: A Selective Estrogen Receptor Modulator (SERM) with Multiple Target System Effects
Muchmore
The Oncologist 2000;5:388-392.
ABSTRACT | FULL TEXT  

The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease
Mosca
Arch Intern Med 2000;160:2263-2272.
ABSTRACT | FULL TEXT  

Reducing the Risk of Breast Cancer
Chlebowski
NEJM 2000;343:191-198.
FULL TEXT  

Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women
Herrington et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:1606-1612.
ABSTRACT | FULL TEXT  

Oral, but Not Transdermal, Administration of Estrogens Lowers Tissue-Type Plasminogen Activator Levels in Humans Without Affecting Endothelial Synthesis
Giltay et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:1396-1403.
ABSTRACT | FULL TEXT  

Postmenopausal Hormone Replacement Therapy Increases Coagulation Activity and Fibrinolysis
Teede et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:1404-1409.
ABSTRACT | FULL TEXT  

The Effects of Hormone Replacement Therapy and Raloxifene on C-Reactive Protein and Homocysteine in Healthy Postmenopausal Women: A Randomized, Controlled Trial
Walsh et al.
J. Clin. Endocrinol. Metab. 2000;85:214-218.
ABSTRACT | FULL TEXT  

Selective Estrogen Receptor Modulators (SERMs) in Clinical Practice
louffe
Reproductive Sciences 2000;7:S38-S46.
ABSTRACT  

Both Raloxifene and Estrogen Reduce Major Cardiovascular Risk Factors in Healthy Postmenopausal Women : A 2-Year, Placebo-Controlled Study
de Valk-de Roo et al.
Arterioscler. Thromb. Vasc. Bio. 1999;19:2993-3000.
ABSTRACT | FULL TEXT  

Cardiovascular Actions of Estrogens in Men
Sudhir and Komesaroff
J. Clin. Endocrinol. Metab. 1999;84:3411-3415.
FULL TEXT  

Raloxifene as a multifunctional medicine?
Jordan and Morrow
BMJ 1999;319:331-332.
FULL TEXT  

Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women
Col et al.
Arch Intern Med 1999;159:1458-1466.
ABSTRACT | FULL TEXT  

The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial
Cummings et al.
JAMA 1999;281:2189-2197.
ABSTRACT | FULL TEXT  

Encouraging News From the SERM Frontier
Franks and Steinberg
JAMA 1999;281:2243-2244.
FULL TEXT  

The Protective Effects of Estrogen on the Cardiovascular System
Mendelsohn and Karas
NEJM 1999;340:1801-1811.
FULL TEXT  

Tamoxifen, Raloxifene, and the Prevention of Breast Cancer
Jordan and Morrow
Endocr. Rev. 1999;20:253-278.
ABSTRACT | FULL TEXT  

Selective Estrogen Receptor Modulators: Clinical Spectrum
Cosman and Lindsay
Endocr. Rev. 1999;20:418-434.
ABSTRACT | FULL TEXT  

American Society of Clinical Oncology Technology Assessment on Breast Cancer Risk Reduction Strategies: Tamoxifen and Raloxifene
Chlebowski et al.
JCO 1999;17:1939-1939.
ABSTRACT | FULL TEXT  

The Individualized Approach to Menopause Management
Walsh
J. Clin. Endocrinol. Metab. 1999;84:1900-1904.
FULL TEXT  

{blacktriangledown}Raloxifene to prevent postmenopausal osteoporosis
DTB 1999;37:33-36.
ABSTRACT | FULL TEXT  

Clinical Effects of Raloxifene Hydrochloride in Women
Khovidhunkit and Shoback
ANN INTERN MED 1999;130:431-439.
ABSTRACT | FULL TEXT  

Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein
Nilausen and Meinertz
Am. J. Clin. Nutr. 1999;69:419-425.
ABSTRACT | FULL TEXT  

Raloxifene Lowers LDL and Total Cholesterol
JWatch Women's Health 1998;1998:16-16.
FULL TEXT  

Raloxifene and Cardiovascular Risk in Postmenopausal Women
JWatch General 1998;1998:2-2.
FULL TEXT  

Of Designer Drugs, Magic Bullets, and Gold Standards
Rifkind and Rossouw
JAMA 1998;279:1483-1485.
FULL TEXT