Estrogen replacement therapy and the risk of venous thrombosis

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Abstract

purpose: Estrogen replacement therapy is believed by many physicians to cause thrombophlebitis and to be contraindicated in women at risk for this disease. However, clinical data supporting this assumption are scant, and further investigation is required.

patients and methods: We tested the estrogen-thrombophlebitis association in a case-control study. Charts of all consecutive women aged 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism were reviewed; 121 cases and 236 controls matched for age, year of admission, admitting service, and socioeconomic status were obtained. Hormone use and nonuse were validated in a subset of randomly selected women.

results: Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls). Other analyses that variously excluded women with a past history of thrombosis, women less than 50 years of age, women with thrombosis occurring after admission, and women whose estrogen use was indeterminate also did not support an increased risk of thrombotic disease. Adjustment for the presence of independent thrombotic risk factors did not alter the odds ratio for estrogen use.

conclusion: This case-control study of older women, unselected for other thrombotic risk factors, does not support the commonly held assumption that replacement estrogen increases the risk of venous thrombosis.

References (50)

  • RD Gambrell

    The menopause: benefits and risks of estrogen-progestogen replacement therapy

    Fertil Steril

    (1982)
  • B Ettinger

    Prevention of osteoporosis: treatment of estradiol deficiency

    Obstet Gynecol

    (1988)
  • DP Kiel et al.

    Hip fracture and the use of estrogens in postmenopausal women

    N Engl J Med

    (1987)
  • RL Prince et al.

    Prevention of postmenopausal osteoporosis: a comparative study of exercise, calcium supplementation, and hormonereplacement therapy

    N Engl J Med

    (1991)
  • E Barrett-Connor et al.

    Estrogen use and coronary heart disease in women

    JAMA

    (1991)
  • RA Lobo

    Cardiovascular implications of estrogen replacement therapy

    Obstet Gynecol

    (1990)
  • MJ Stampfer et al.

    Postmenopausal estrogen therapy and cardiovascular disease

    N Engl J Med

    (1991)
  • BW Walsh et al.

    Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins

    N Engl J Med

    (1991)
  • BE Henderson et al.

    Decreased mortality in users of estrogen replacement therapy

    Arch Intern Med

    (1991)
  • HK Ziel et al.

    Increased risk of endometrial carcinoma among users of conjugated estrogens

    N Engl J Med

    (1975)
  • TM Mack et al.

    Estrogens and endometrial cancer in a retirement community

    N Engl J Med

    (1976)
  • CMF Antunes et al.

    Endometrial cancer and estrogen use

    N Engl J Med

    (1979)
  • The Boston Collaborative Drug Surveillance Program

    Surgically confirmed gallbladder disease, venous thromboembolism and breast tumors in relation to postmenopausal estrogen therapy

    N Engl J Med

    (1974)
  • E Barrett-Connor

    Putative complications of estrogen replacement therapy: hypertension, diabetes, thrombophlebitis, and gallstones

  • LE Nachtigall et al.

    Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems

    Obstet Gynecol

    (1979)
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    This research was supported in part by the National Institutes of Health and the National Heart, Lung and Blood Institute Grant 1U01-HL40207. This work was presented in abstract form at the Annual Meeting of the Society of General Internal Medicine, Arlington, Virginia, May 1990.

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