Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias

Arch Intern Med. 1999 Jan 11;159(1):65-70. doi: 10.1001/archinte.159.1.65.


Background: The magnitude of the relative risk of venous thrombosis caused by low-dose oral contraceptive use is still debated because previous studies might have been affected by diagnostic suspicion and referral bias.

Methods: We conducted a case-control study in which the effect of diagnostic suspicion and referral bias was excluded. The study was performed in 2 diagnostic centers to which patients with clinically suspected deep vein thrombosis of the leg were referred. History of oral contraceptive use was obtained before objective testing for thrombosis. Young females with an objective diagnosis of deep vein thrombosis were considered case patients, and those who were referred with the same clinical suspicion but who had no thrombosis served as control subjects. Participants were seen between September 1, 1982, and October 18, 1995: 185 consecutive patients and 591 controls aged 15 to 49 years with a first episode of venous thrombosis and without malignant neoplasms, pregnancy, or known inherited clotting defects.

Results: The overall odds ratio for oral contraceptive use was 3.2 (95% confidence interval [CI], 2.3-4.5); after adjustment for age, family history of venous thrombosis, calendar time, and center, the odds ratio was 3.9 (95% CI, 2.6-5.7). In the idiopathic group (120 patients and 413 controls, excluding recent surgery, trauma, or immobilization), the odds ratio for oral contraceptive use was 3.8 (95% CI, 2.5-5.9); after adjustment, the odds ratio was 5.0 (95% CI, 3.1-8.2).

Conclusions: In this study, in which patients and controls were subj ect to the same referral and diagnostic procedures, we found similar relative risk estimates for oral contraceptive use as in previous studies. We conclude that diagnostic suspicion and referral bias did not play an important role in previous studies and that the risk of venous thrombosis with use of current brands of oral contraceptives still exists.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Bias
  • Case-Control Studies
  • Contraceptives, Oral / administration & dosage
  • Contraceptives, Oral / adverse effects*
  • Diagnosis, Differential
  • Female
  • Humans
  • Leg / blood supply
  • Middle Aged
  • Netherlands / epidemiology
  • Odds Ratio
  • Referral and Consultation
  • Risk Factors
  • Venous Thrombosis / chemically induced*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / epidemiology*


  • Contraceptives, Oral