 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
2 May 2000 | Volume 132 Issue 9 | Pages 689-696
Background: Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited.
Objective: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: 20 clinical centers in the United States.
Participants: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy.
Intervention: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383).
Measurements: Documented deep venous thrombosis or pulmonary embolism.
Results: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]).
Conclusions: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.
Author and Article Information
From the University of California, San Francisco, San Francisco, California; Emory University School of Medicine, Atlanta, Georgia; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Cedars-Sinai Medical Center, Los Angeles, California; and University of Minnesota, Minneapolis, Minnesota.
Acknowledgments: The authors thank Josephine Fong for performing statistical analyses.
Grant Support: By Wyeth-Ayerst Laboratories.
Requests for Single Reprints: Deborah Grady, MD, MPH, University of California, San Francisco, 74 New Montgomery Street, Suite 600, San Francisco, CA 94105.
Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.
Current Author Addresses: Drs. Grady, Vittinghoff, and Hulley: University of California, San Francisco, 74 New Montgomery Street, Suite 600, San Francisco, CA 94105.
Dr. Wenger: Emory University School of Medicine, 69 Butler Street SE, Atlanta, GA 30303.
Drs. Herrington and Furberg: Wake Forest University School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1066.
Dr. Khan: Cedars-Sinai Medical Center, 444 South San Vicente Boulevard, Suite 903, Los Angeles, CA 90048-4174.
Dr. Hunninghake: Heart Disease Prevention Clinic, Box 192, 151 Variety Club Heart and Research Center, 401 East River Parkway, Minneapolis, MN 55455.
Author Contributions: Conception and design: D. Grady, N.K. Wenger, S. Hulley.
Analysis and interpretation of the data: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, E. Vittinghoff, S. Hulley.
Drafting of the article: D. Grady.
Critical revision of the article for important intellectual content: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, S. Hulley.
Final approval of the article: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, E. Vittinghoff, S. Hulley.
Provision of study materials or patients: N.K. Wenger, D. Herrington, S. Khan, D. Hunninghake.
Statistical expertise: E. Vittinghoff, S. Hulley.
Obtaining of funding: D. Grady, C. Furberg, D. Hunninghake, S. Hulley.
Administrative, technical, or logistic support: D. Grady, S. Hulley.
Collection and assembly of data: D. Grady, S. Khan. ARTICLE
Postmenopausal Hormone Therapy Increases Risk for Venous Thromboembolic Disease: The Heart and Estrogen/progestin Replacement Study
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  S. Rathbun Venous thromboembolism in women Vascular Medicine, August 1, 2008; 13(3): 255 - 266. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Matyal Newly Appreciated Pathophysiology of Ischemic Heart Disease in Women Mandates Changes in Perioperative Management: A Core Review Anesth. Analg., July 1, 2008; 107(1): 37 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. F. Tapson Acute Pulmonary Embolism N. Engl. J. Med., March 6, 2008; 358(10): 1037 - 1052. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Heit The Epidemiology of Venous Thromboembolism in the Community Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 370 - 372. [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Rebbeck, A. B. Troxel, S. Norman, G. Bunin, A. DeMichele, R. Schinnar, J. A. Berlin, and B. L. Strom Pharmacogenetic Modulation of Combined Hormone Replacement Therapy by Progesterone-Metabolism Genotypes in Postmenopausal Breast Cancer Risk Am. J. Epidemiol., December 15, 2007; 166(12): 1392 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Aschbacher, R. von Kanel, P. J. Mills, S. Hong, S. K. Roepke, B. T. Mausbach, T. L. Patterson, M. G. Ziegler, J. E. Dimsdale, S. Ancoli-Israel, et al. Combination of Caregiving Stress and Hormone Replacement Therapy is Associated With Prolonged Platelet Activation to Acute Stress Among Postmenopausal Women Psychosom Med, November 1, 2007; 69(9): 910 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Glynn, P. M Ridker, S. Z. Goldhaber, and J. E. Buring Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism: A Randomized Trial Ann Intern Med, October 16, 2007; 147(8): 525 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Yegen, D. J. Lederer, R. G. Barr, J. S. Wilt, Y. Fang, E. Bagiella, F. D'Ovidio, J. M. Okun, J. R. Sonett, S. M. Arcasoy, et al. Risk Factors for Venous Thromboembolism After Lung Transplantation Chest, August 1, 2007; 132(2): 547 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Ray, C. Kearon, Q. Yi, P. Sheridan, E. Lonn, and for the Heart Outcomes Prevention Evaluation 2 (HO Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism: A Randomized Trial Ann Intern Med, June 5, 2007; 146(11): 761 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wierman and W. M. Kohrt Review Article: Vascular and Metabolic Effects of Sex Steroids: New Insights Into Clinical Trials Reproductive Sciences, May 1, 2007; 14(4): 300 - 314. [Abstract] [PDF]
|
|
|
|
 |
|
 T. R. Rebbeck, A. B. Troxel, Y. Wang, A. H. Walker, S. Panossian, S. Gallagher, E. G. Shatalova, R. Blanchard, G. Bunin, A. DeMichele, et al. Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. J Natl Cancer Inst, September 20, 2006; 98(18): 1311 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Bushnell, P. Hurn, C. Colton, V. M. Miller, G. del Zoppo, M. S.V. Elkind, B. Stern, D. Herrington, G. Ford-Lynch, P. Gorelick, et al. Advancing the Study of Stroke in Women: Summary and Recommendations for Future Research From an NINDS-Sponsored Multidisciplinary Working Group Stroke, September 1, 2006; 37(9): 2387 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Abramson, J. P. Costantino, J. E. Garber, N. Berliner, D. L. Wickerham, and N. Wolmark Effect of Factor V Leiden and Prothrombin G20210->A Mutations on Thromboembolic Risk in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. J Natl Cancer Inst, July 5, 2006; 98(13): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Christian, P. Y. Liu, S. Harrington, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Intimal Estrogen Receptor (ER){beta}, But Not ER{alpha} Expression, Is Correlated with Coronary Calcification and Atherosclerosis in Pre- and Postmenopausal Women J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2713 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hemelaar, J. Rosing, P. Kenemans, M. C. L.G.D. Thomassen, D. D.M. Braat, and M. J. van der Mooren Less Effect of Intranasal Than Oral Hormone Therapy on Factors Associated With Venous Thrombosis Risk in Healthy Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1660 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mineo, H. Deguchi, J. H. Griffin, and P. W. Shaul Endothelial and Antithrombotic Actions of HDL Circ. Res., June 9, 2006; 98(11): 1352 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Q. Purnell, L. B. Bland, M. Garzotto, D. Lemmon, E. M. Wersinger, C. W. Ryan, J. D. Brunzell, and T. M. Beer Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer J. Lipid Res., February 1, 2006; 47(2): 349 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Petitti and D. A. Freedman Invited Commentary: How Far Can Epidemiologists Get with Statistical Adjustment? Am. J. Epidemiol., September 1, 2005; 162(5): 415 - 418. [Full Text] [PDF]
|
|
|
|
 |
|
 S R Davis, I Dinatale, L Rivera-Woll, and S Davison Postmenopausal hormone therapy: from monkey glands to transdermal patches J. Endocrinol., May 1, 2005; 185(2): 207 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jayachandran, R. Mukherjee, T. Steinkamp, P. LaBreche, M. P. Bracamonte, H. Okano, W. G. Owen, and V. M. Miller Differential effects of 17{beta}-estradiol, conjugated equine estrogen, and raloxifene on mRNA expression, aggregation, and secretion in platelets Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2355 - H2362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Petitti New hope for hormone replacement and the heart? J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1246 - 1248. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Chatrath, K. L. Ronningen, P. LaBreche, S. R. Severson, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Effect of puberty on coronary arteries from female pigs J Appl Physiol, October 1, 2003; 95(4): 1672 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Duggirala, D. A. Cook, K. F. Mauck, Y. F. Tai, P. Prandoni, A. W.A. Lensing, and M. H. Prins An Association between Atherosclerosis and Venous Thrombosis N. Engl. J. Med., July 24, 2003; 349(4): 401 - 402. [Full Text] [PDF]
|
|
|
|
 |
|
 S S Pierangeli and E N Harris Probing antiphospholipid-mediated thrombosis: the interplay between anticardiolipin antibodies and endothelial cells Lupus, July 1, 2003; 12(7): 539 - 545. [Abstract] [PDF]
|
|
|
|
|
|
M. S. Post, M. Christella, L.G.D. Thomassen, M. J. van der Mooren, W. M. van Baal, J. Rosing, P. Kenemans, and C. D.A. Stehouwer Effect of Oral and Transdermal Estrogen Replacement Therapy on Hemostatic Variables Associated With Venous Thrombosis: A Randomized, Placebo-Controlled Study in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1116 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Prandoni, F. Bilora, A. Marchiori, E. Bernardi, F. Petrobelli, A. W.A. Lensing, M. H. Prins, and A. Girolami An Association between Atherosclerosis and Venous Thrombosis N. Engl. J. Med., April 10, 2003; 348(15): 1435 - 1441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Okada, S. Nomura, Y. Ikoma, E. Yamamoto, T. Ito, T. Mitsui, K. Tamakoshi, and S. Mizutani Effects of Postmenopausal Hormone Replacement Therapy on HbA1c Levels Diabetes Care, April 1, 2003; 26(4): 1088 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Brown and R. G. Josse Lignes directrices de pratique clinique 2002 pour le diagnostic et le traitement de l'osteoporose au Canada Can. Med. Assoc. J., March 18, 2003; 168(90060): SF1 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rymer, R. Wilson, and K. Ballard Making decisions about hormone replacement therapy BMJ, February 8, 2003; 326(7384): 322 - 326. [Full Text] [PDF]
|
|
|
|
|
|
M. P. Bracamonte, M. Jayachandran, K. S. Rud, and V. M. Miller Acute effects of 17beta -estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2389 - H2396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang-Cheng and J. A. Rosenfeld Hormone replacement therapy BMJ, November 27, 2002; (2002) 2090003. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Brown and R. G. Josse 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada Can. Med. Assoc. J., November 12, 2002; 167(90100): s1 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Liu, S.-H. Yang, E. Perez, K. D. Yi, S. S. Wu, K. Eberst, L. Prokai, K. Prokai-Tatrai, Z. Y. Cai, D. F. Covey, et al. Neuroprotective Effects of a Novel Non-Receptor-Binding Estrogen Analogue: In Vitro and In Vivo Analysis Stroke, October 1, 2002; 33(10): 2485 - 2491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Decensi, U. Omodei, C. Robertson, B. Bonanni, A. Guerrieri-Gonzaga, F. Ramazzotto, H. Johansson, S. Mora, M. T. Sandri, M. Cazzaniga, et al. Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women Circulation, September 3, 2002; 106(10): 1224 - 1228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Speroff The Impact of the Women's Health Initiative on Clinical Practice Reproductive Sciences, September 1, 2002; 9(5): 251 - 253. [PDF]
|
|
|
|
|
|
D. L. DeMets and R. M. Califf Lessons Learned From Recent Cardiovascular Clinical Trials: Part II Circulation, August 13, 2002; 106(7): 880 - 886. [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Group for the Women's Health Initiative In Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial JAMA, July 17, 2002; 288(3): 321 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grady, D. Herrington, V. Bittner, R. Blumenthal, M. Davidson, M. Hlatky, J. Hsia, S. Hulley, A. Herd, S. Khan, et al. Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II) JAMA, July 3, 2002; 288(1): 49 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hulley, C. Furberg, E. Barrett-Connor, J. Cauley, D. Grady, W. Haskell, R. Knopp, M. Lowery, S. Satterfield, H. Schrott, et al. Noncardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II) JAMA, July 3, 2002; 288(1): 58 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Petitti Hormone Replacement Therapy for Prevention: More Evidence, More Pessimism JAMA, July 3, 2002; 288(1): 99 - 101. [Full Text] [PDF]
|
|
|
|
|
|
M. Jayachandran and V. M. Miller Ovariectomy upregulates expression of estrogen receptors, NOS, and HSPs in porcine platelets Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H220 - H226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Herrington, E. Vittinghoff, F. Lin, J. Fong, F. Harris, D. Hunninghake, V. Bittner, H. G. Schrott, R. S. Blumenthal, R. Levy, et al. Statin Therapy, Cardiovascular Events, and Total Mortality in the Heart and Estrogen/Progestin Replacement Study (HERS) Circulation, June 25, 2002; 105(25): 2962 - 2967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Herrington, E. Vittinghoff, T. D. Howard, D. A. Major, J. Owen, D. M. Reboussin, D. Bowden, V. Bittner, J. A. Simon, D. Grady, et al. Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 1012 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Grady A 60-Year-Old Woman Trying to Discontinue Hormone Replacement Therapy JAMA, April 24, 2002; 287(16): 2130 - 2137. [Full Text] [PDF]
|
|
|
|
|
|
E. Barrett-Connor, D. Grady, A. Sashegyi, P. W. Anderson, D. A. Cox, K. Hoszowski, P. Rautaharju, K. D. Harper, and for the MORE Investigators Raloxifene and Cardiovascular Events in Osteoporotic Postmenopausal Women: Four-Year Results From the MORE (Multiple Outcomes of Raloxifene Evaluation) Randomized Trial JAMA, February 20, 2002; 287(7): 847 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E Rossouw Hormones, genetic factors, and gender differences in cardiovascular disease Cardiovasc Res, February 15, 2002; 53(3): 550 - 557. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Hlatky, D. Boothroyd, E. Vittinghoff, P. Sharp, M. A. Whooley, and for the HERS Research Group Quality-of-Life and Depressive Symptoms in Postmenopausal Women After Receiving Hormone Therapy: Results From the Heart and Estrogen/Progestin Replacement Study (HERS) Trial JAMA, February 6, 2002; 287(5): 591 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Rexrode and J. E. Manson Postmenopausal Hormone Therapy and Quality of Life: No Cause for Celebration JAMA, February 6, 2002; 287(5): 641 - 642. [Full Text] [PDF]
|
|
|
|
|
|
F.R. Rosendaal, F.M. Helmerhorst, and J.P. Vandenbroucke Female Hormones and Thrombosis Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 201 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Waters Estrogen therapy for unstable angina: Another bump for the bandwagon J. Am. Coll. Cardiol., January 16, 2002; 39(2): 238 - 240. [Full Text] [PDF]
|
|
|
|
|
|
S. E. McNagny, N. K. Wenger, N. Hilmy, S. Banarer, M. Barton, R. K. Dubey, S. R. Davis, J. E. Manson, and K. A. Martin Postmenopausal Hormone-Replacement Therapy N. Engl. J. Med., January 3, 2002; 346(1): 63 - 65. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hedblad, J. Merlo, J. Manjer, G. Engstrom, G. Berglund, and L. Janzon Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy Scand J Public Health, January 1, 2002; 30(1): 12 - 19. [Abstract] [PDF]
|
|
|
|
|
|
D. M. Herrington and K. P. Klein Genome and Hormones: Gender Differences in Physiology: Invited Review: Pharmacogenetics of estrogen replacement therapy J Appl Physiol, December 1, 2001; 91(6): 2776 - 2784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lewis, M. P. Bracamonte, K. S. Rud, and V. M. Miller Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Effects of sex and ovariectomy on responses to platelets in porcine femoral veins J Appl Physiol, December 1, 2001; 91(6): 2823 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Angeja, M. G. Shlipak, A. S. Go, S. C. Johnston, P. D. Frederick, J. G. Canto, H. V. Barron, D. Grady, and for the National Registry of Myocardial Infarction Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1297 - 1301. [Abstract] [Full Text] [PDF]
|
Article
