Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus | Venous Thromboembolism | JAMA Internal Medicine | JAMA Network
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1.
White  RH The epidemiology of venous thromboembolism.  Circulation 2003;107 ((23 suppl 1)) I4- I8PubMedGoogle ScholarCrossref
2.
Cushman  M Effects of estrogen and selective estrogen receptor modulators on hemostasis and inflammation.  Ann N Y Acad Sci 2001;949175- 180PubMedGoogle ScholarCrossref
3.
Peverill  RE Hormone therapy and venous thromboembolism.  Best Pract Res Clin Endocrinol Metab 2003;17149- 164PubMedGoogle ScholarCrossref
4.
Daly  EVessey  MPHawkins  MMCarson  JLGough  PMarsh  S Risk of venous thromboembolism in users of hormone replacement therapy.  Lancet 1996;348977- 980PubMedGoogle ScholarCrossref
5.
Grady  DHulley  SBFurberg  C Venous thromboembolic events associated with hormone replacement therapy [letter].  JAMA 1997;278477PubMedGoogle ScholarCrossref
6.
Grodstein  FStampfer  MJGoldhaber  SZ  et al.  Prospective study of exogenous hormones and risk of pulmonary embolism in women.  Lancet 1996;348983- 987PubMedGoogle ScholarCrossref
7.
Jick  HDerby  LEMyers  MWVasilakis  CNewton  KM Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens.  Lancet 1996;348981- 983PubMedGoogle ScholarCrossref
8.
Perez Gutthann  SGarcia Rodriguez  LACastellsague  JDuque Oliart  A Hormone replacement therapy and risk of venous thromboembolism: population based case-control study.  BMJ 1997;314796- 800PubMedGoogle ScholarCrossref
9.
Varas-Lorenzo  CGarcia-Rodriguez  LACattaruzzi  CTroncon  MGAgostini  LPerez-Gutthann  S Hormone replacement therapy and the risk of hospitalization for venous thromboembolism.  Am J Epidemiol 1998;147387- 390PubMedGoogle ScholarCrossref
10.
Tsai  AWCushman  MRosamond  WDHeckbert  SRPolak  JFFolsom  AR Cardiovascular risk factors and venous thromboembolism incidence.  Arch Intern Med 2002;1621182- 1189PubMedGoogle ScholarCrossref
11.
Herrington  DMVittinghoff  EHoward  TD  et al.  Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease.  Arterioscler Thromb Vasc Biol 2002;221012- 1017PubMedGoogle ScholarCrossref
12.
Rosendaal  FRHelmerhorst  FMVandenbroucke  JP Female hormones and thrombosis.  Arterioscler Thromb Vasc Biol 2002;22201- 210PubMedGoogle ScholarCrossref
13.
Cushman  MKuller  LHPrentice  R  et al.  Estrogen plus progestin and risk of venous thrombosis.  JAMA 2004;2921573- 1580PubMedGoogle ScholarCrossref
14.
Rossouw  JEAnderson  GLPrentice  RL  et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women.  JAMA 2002;288321- 333PubMedGoogle ScholarCrossref
15.
Herrington  DMReboussin  DMBrosnihan  KB  et al.  Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.  N Engl J Med 2000;343522- 529PubMedGoogle ScholarCrossref
16.
Hoibraaten  EAbdelnoor  MSandset  PM Hormone replacement therapy with estradiol and risk of venous thromboembolism—a population-based case-control study.  Thromb Haemost 1999;821218- 1221PubMedGoogle Scholar
17.
Anderson  GLLimacher  MAssaf  AR  et al.  Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.  JAMA 2004;2911701- 1712PubMedGoogle ScholarCrossref
18.
The Women's Health Initiative Study Group, Design of the Women's Health Initiative clinical trial and observational study.  Control Clin Trials 1998;1961- 109PubMedGoogle ScholarCrossref
19.
Curb  JDMcTiernan  AHeckbert  SR  et al.  Outcomes ascertainment and adjudication methods in the Women's Health Initiative.  Ann Epidemiol 2003;13 ((9 suppl)) S122- S128PubMedGoogle ScholarCrossref
20.
Grady  DWenger  NKHerrington  D  et al.  Postmenopausal hormone therapy increases risk for venous thromboembolic disease: the Heart and Estrogen/progestin Replacement Study.  Ann Intern Med 2000;132689- 696PubMedGoogle ScholarCrossref
21.
Cuzick  JForbes  JEdwards  R  et al.  First results from the International Breast Cancer Intervention Study (IBIS-I).  Lancet 2002;360817- 824PubMedGoogle ScholarCrossref
22.
Ettinger  BBlack  DMMitlak  BH  et al. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators, Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene.  JAMA 1999;282637- 645[Published Erratum Appears In Jama. 1999;282:2124]PubMedGoogle ScholarCrossref
23.
Fisher  BCostantino  JPWickerham  DL  et al.  Tamoxifen for prevention of breast cancer.  J Natl Cancer Inst 1998;901371- 1388PubMedGoogle ScholarCrossref
24.
Miller  JChan  BKNelson  HD Postmenopausal estrogen replacement and risk for venous thromboembolism.  Ann Intern Med 2002;136680- 690PubMedGoogle ScholarCrossref
25.
Abdollahi  MCushman  MRosendaal  FR Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.  Thromb Haemost 2003;89493- 498PubMedGoogle Scholar
26.
Samama  MM An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study.  Arch Intern Med 2000;1603415- 3420PubMedGoogle ScholarCrossref
27.
Helmerhorst  FMBloemenkamp  KWRosendaal  FRVandenbroucke  JP Oral contraceptives and thrombotic disease.  Thromb Haemost 1997;78327- 333PubMedGoogle Scholar
28.
Daly  EVessey  MPPainter  RHawkins  MM Case-control study of venous thromboembolism risk in users of hormone replacement therapy [letter].  Lancet 1996;3481027PubMedGoogle ScholarCrossref
29.
Smith  NLHeckbert  SRLemaitre  RN  et al.  Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis.  JAMA 2004;2921581- 1587PubMedGoogle ScholarCrossref
30.
Hoibraaten  EQvigstad  EArnesen  HLarsen  SWickstrom  ESandset  PM Increased risk of recurrent venous thromboembolism during hormone replacement therapy—results of the randomized, double-blind, placebo-controlled Estrogen in Venous Thromboembolism Trial (EVTET).  Thromb Haemost 2000;84961- 967PubMedGoogle Scholar
31.
 Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial.  Lancet 2000;3551295- 1302PubMedGoogle ScholarCrossref
32.
Middeldorp  SMeinardi  JRKoopman  MM  et al.  A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.  Ann Intern Med 2001;135322- 327PubMedGoogle ScholarCrossref
Original Investigation
April 10, 2006

Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus

Author Affiliations

Author Affiliations: University of Hawaii and Pacific Health Research Institute, Honolulu (Dr Curb); Fred Hutchinson Cancer Research Center (Dr Prentice and Ms Rodabough) and University of Washington (Dr Prentice), Seattle, Wash; Baylor College of Medicine, Houston, Tex (Dr Bray); University of California at San Diego, La Jolla/Chula Vista (Dr Langer); Northwestern University, Evanston, Ill (Dr Van Horn); Medical College of Wisconsin, Milwaukee (Dr Barnabei); University of Nevada School of Medicine, Reno (Dr Bloch); Brown Medical School, Providence, RI (Dr Cyr); University of Cincinnati, Cincinnati, Ohio (Dr Gass); Boulder Women's Care, Boulder, Colo (Dr Lepine); Kaiser Permanente Division of Research, Oakland, Calif (Dr Sidney); MedStar Research Institute, Hyattsville, Md (Dr Uwaifo); and Leiden University Medical Center, Leiden, the Netherlands (Dr Rosendaal).

Arch Intern Med. 2006;166(7):772-780. doi:10.1001/archinte.166.7.772
Abstract

Background  Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited.

Methods  The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo.

Results  During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors.

Conclusion  An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.

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