Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives

Contraception. 2004 Jul;70(1):3-10. doi: 10.1016/j.contraception.2004.02.010.


Objective: To assess the relationship between venous thromboembolic disease (VTE) and use of low-estrogen dose (<50 microg) combined estrogen-progestin oral contraceptives (OC) and three thrombosis-related gene mutations in a United States population.

Design: This case-control study was conducted in 1998-2000 among women ages 15-44 years who were members of the Kaiser Permanente Medical Care Program [KPMCP] (Northern and Southern California). Cases were women with incident VTE; about three times as many women frequency matched for age were randomly selected as controls from the KPMCP membership in the same years. Data were collected in a 1 h face-to-face interview; blood was drawn to extract DNA to test for gene polymorphisms. The analysis data set comprised 196 cases (mean age 35.3 years) and 746 controls (mean age 36.2 years).

Results: The adjusted odds ratio (OR) for VTE associated with current OC use was 4.07 (95% confidence interval [CI]: 2.77-6.00). The OR associated with OC use was higher for women who were obese than in the nonobese (p = 0.01 for likelihood test for interaction) and in women without predisposing medical conditions (p = 0.02 for interaction). The adjusted OR for VTE was 7.10 (95% CI: 2.33-21.61) in women with factor V Leiden (G1691A) mutation, 2.83 (95% CI: 0.70-11.63) in women with prothrombin G20210A mutation and 0.26 (95% CI: 0.10-0.65) in women with the MTHFR C677T mutation. The OR for VTE in OC users with factor V Leiden mutation (11.32) was elevated more than in OC users without the mutation (3.20) and women with the mutation who were non-OC users (8.42), but confidence intervals overlapped.

Conclusions: The risk of VTE is increased in users of low-estrogen OC formulations. Obese women appear to be at greater risk of VTE when using OCs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Confidence Intervals
  • Contraceptives, Oral, Combined / adverse effects*
  • Contraceptives, Oral, Combined / chemistry
  • Estrogens / administration & dosage*
  • Estrogens / adverse effects
  • Factor V / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Interviews as Topic
  • Mutation
  • Obesity / complications
  • Odds Ratio
  • Progestins / administration & dosage
  • Prothrombin / metabolism
  • Risk Factors
  • Venous Thrombosis / chemically induced*
  • Venous Thrombosis / genetics*


  • Contraceptives, Oral, Combined
  • Estrogens
  • Progestins
  • factor V Leiden
  • Factor V
  • Prothrombin