Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease

Am J Epidemiol. 1991 Jan;133(1):32-7. doi: 10.1093/oxfordjournals.aje.a115799.


Despite the well-recognized association between oral contraceptives and deep venous thromboembolism, little is known about the risks associated with currently marketed formulations containing less than 50 micrograms of estrogen. To assess the venous thrombogenicity of low-estrogen oral contraceptives (those containing less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations, we conducted a cohort study of oral contraceptive users between the ages of 15 and 44 years in the Michigan Medicaid population. The period of the study was from 1980 through the third quarter of 1986. A total of 2,739,400 oral contraceptive prescriptions received by 234,218 women were analyzed. Using the low-estrogen cohort as the referent group, the age and calendar period adjusted relative risk of venous thromboembolism in users of intermediate-dose formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p = 0.06). These data provide evidence that the dose-response relation between oral contraceptive estrogen and venous thromboembolism extends from 50 to 30 micrograms of estrogen, the dose range of currently marketed formulations.

MeSH terms

  • Chemistry, Pharmaceutical / statistics & numerical data*
  • Confounding Factors, Epidemiologic
  • Contraceptives, Oral / administration & dosage*
  • Estrogens / administration & dosage*
  • Female
  • Humans
  • Risk Factors
  • Thromboembolism / chemically induced
  • Thromboembolism / epidemiology*


  • Contraceptives, Oral
  • Estrogens