Contraceptives and cerebral thrombosis: a five-year national case-control study

Contraception. 2002 Mar;65(3):197-205. doi: 10.1016/s0010-7824(01)00306-7.


The object of this study was to assess the influence of oral contraceptives (OCs) on the risk of cerebral thromboembolic attacks (CTA) including thrombotic stroke and transitory cerebral ischemic attacks. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old suffering a first ever CTA during the period January 1, 1994 to December 31, 1998, were included. Controls were selected annually, 600 per year in 1994-1995, 1200 per year 1996-1998. Response rates for cases and controls were 88% and 90%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic diseases, 626 cases and 4054 controls were available for analysis. A multivariate matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustments were made for the following potential confounders: year, length of OC use, smoking, hypertension, migraine, family CTA, and years of schooling. There were 212 and 1208 current users of OCs among cases and controls, respectively. The risk of CTA among current users of OCs decreased significantly with decreasing estrogen dose (nonusers reference): OCs with 50 microg, 30-40 microg, 20 microg ethinyl estradiol (EE) and progestin-only pills implied adjusted odds ratios (ORs) (95% CI) of 4.5 (2.6-7.7), 1.6 (1.3-2.0), 1.7 (1.0-3.1), and 1.0 (0.3-3.0), respectively. Current users of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins combined with 20-30 microg EE had ORs of CTA of 2.2 (1.6-3.0) and 1.4 (1.0-1.9), respectively. After correction for differences in estrogen dose, the third- to second-generation risk ratio was 0.6 (0.4-0.9; p = 0.01). In conclusion, high dose OCs and OCs with second-generation progestins were associated with the risk of CTA. The risk increased 2.5 times with estrogen dose increasing from 20 to 50 microg EE, and users of low-dose OCs with second-generation progestins had a 61% higher risk-association of CTA than users of OCs with third-generation progestins.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bias
  • Brain Ischemia / chemically induced
  • Brain Ischemia / epidemiology
  • Contraceptives, Oral / administration & dosage
  • Contraceptives, Oral / adverse effects*
  • Denmark / epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Intracranial Thrombosis / chemically induced*
  • Intracranial Thrombosis / epidemiology
  • Multivariate Analysis
  • Reproducibility of Results
  • Risk Factors
  • Stroke / chemically induced
  • Stroke / epidemiology


  • Contraceptives, Oral