Skip to main content
The BMJ logoLink to The BMJ
. 1993 Apr 10;306(6883):956–963. doi: 10.1136/bmj.306.6883.956

Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study.

O Lidegaard 1
PMCID: PMC1677472  PMID: 8490470

Abstract

OBJECTIVE--To assess the risk of cerebral thromboembolism in women using low dose oral contraceptives. DESIGN--A retrospective case-control study. SETTING--All Danish medical, neurological, neurosurgical, and gynaecological departments. SUBJECTS--All 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack during 1985-9 and 1588 age matched randomly selected controls. RESULTS--Of 692/1584 case/control questionnaires sent out, 590/1396 (85.3%/88.1%) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreliable diagnosis, 40 had had thromboembolic disease previously, 13 were pregnant, and 152 had a disease predisposing to a cerebral thromboembolic attack. Of the 323 cases without a known predisposition, 320 reported use or non-use of oral contraception. Among the 1396 controls, eight refused to participate, were mentally retarded, or lived abroad; 18 returned an uncompleted questionnaire; 17 had had thromboembolic disease previously; 31 were pregnant; and 130 had a disease predisposing to a cerebral thromboembolic attack. Thus 1198 non-predisposed controls were available, among whom 1197 reported use or non-use of oral contraception. Among the 320 cases, 116 (36.3%) were oral contraceptive users at the time of the cerebral thromboembolic attack. By comparison there were 191 users (16.0%) among the 1197 controls, giving a crude odds ratio of 3.0. After multivariate analysis, including confounder control for age, smoking, years of schooling, and trend in use of different types of oral contraceptives during 1985-90, pills containing 50 micrograms oestrogen were associated with an odds ratio for cerebral thromboembolic attack of 2.9 (95% confidence interval 1.6 to 5.4), those containing 30-40 micrograms oestrogen an odds ratio of 1.8 (1.1 to 2.9), those containing progestogen only an odds ratio of 0.9 (0.4 to 2.4). The odds ratio did not change with increasing age or with duration of oral contraceptive use. A 50% increased risk of a cerebral thromboembolic attacks among cigarette smokers (after confounder control) was independent of oral contraception status and age. CONCLUSION--Low dose oral contraceptives are associated with an increased risk of cerebral thromboembolic attack. Combined or sequential pills containing 30-40 micrograms oestrogen are associated with a one third reduced risk compared with preparations containing 50 micrograms oestrogen. Progestogen only pills did not increase the risk of a cerebral thromboembolic attack.

Full text

PDF
958

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abu-Zeid H. A., Choi N. W., Maini K. K., Hsu P. H., Nelson N. A. Relative role of factors associated with cerebral infarction and cerebral hemorrhage. A matched pair case-control study. Stroke. 1977 Jan-Feb;8(1):106–112. doi: 10.1161/01.str.8.1.106. [DOI] [PubMed] [Google Scholar]
  2. Abu-Zeid H. A., Choi N. W., Maini K. K., Nelson N. A. Incidence and epidemiologic features of cerebrovascular disease (stroke) in Manitoba, Canada. Study of population 20-64 years of age. Prev Med. 1975 Dec;4(4):567–578. doi: 10.1016/0091-7435(75)90042-0. [DOI] [PubMed] [Google Scholar]
  3. Aho K., Reunanen A., Aromaa A., Knekt P., Maatela J. Prevalence of stroke in Finland. Stroke. 1986 Jul-Aug;17(4):681–686. doi: 10.1161/01.str.17.4.681. [DOI] [PubMed] [Google Scholar]
  4. Arbuckle D. D., Harris R. I., Goldacre M. J. Stroke in people under 55 years of age. Public Health. 1982 Mar;96(2):96–100. doi: 10.1016/s0033-3506(82)80102-9. [DOI] [PubMed] [Google Scholar]
  5. Boysen G., Nyboe J., Appleyard M., Sørensen P. S., Boas J., Somnier F., Jensen G., Schnohr P. Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke. 1988 Nov;19(11):1345–1353. doi: 10.1161/01.str.19.11.1345. [DOI] [PubMed] [Google Scholar]
  6. Colditz G. A., Bonita R., Stampfer M. J., Willett W. C., Rosner B., Speizer F. E., Hennekens C. H. Cigarette smoking and risk of stroke in middle-aged women. N Engl J Med. 1988 Apr 14;318(15):937–941. doi: 10.1056/NEJM198804143181501. [DOI] [PubMed] [Google Scholar]
  7. Compston J. E., Horton L. W., Laker M. F., Ayers A. B., Woodhead J. S., Bull H. J., Gazet J. C., Pilkington T. R. Bone disease after jejuno-ileal bypass for obesity. Lancet. 1978 Jul 1;2(8079):1–4. doi: 10.1016/s0140-6736(78)91318-1. [DOI] [PubMed] [Google Scholar]
  8. Coulter A., Vessey M., McPherson K., Crossley B. The ability of women to recall their oral contraceptive histories. Contraception. 1986 Feb;33(2):127–137. doi: 10.1016/0010-7824(86)90079-x. [DOI] [PubMed] [Google Scholar]
  9. Doll R., Gray R., Hafner B., Peto R. Mortality in relation to smoking: 22 years' observations on female British doctors. Br Med J. 1980 Apr 5;280(6219):967–971. doi: 10.1136/bmj.280.6219.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fogelholm R., Aho K. Ischaemic cerebrovascular disease in young adults. 1. Smoking habits, use of oral contraceptives, relative weight, blood pressure and electrocardiographic findings. Acta Neurol Scand. 1973;49(4):415–427. doi: 10.1111/j.1600-0404.1973.tb01314.x. [DOI] [PubMed] [Google Scholar]
  11. Gerstman B. B., Piper J. M., Tomita D. K., Ferguson W. J., Stadel B. V., Lundin F. E. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am J Epidemiol. 1991 Jan;133(1):32–37. doi: 10.1093/oxfordjournals.aje.a115799. [DOI] [PubMed] [Google Scholar]
  12. Glass R., Johnson B., Vessey M. Accuracy of recall of histories of oral contraceptive use. Br J Prev Soc Med. 1974 Nov;28(4):273–275. doi: 10.1136/jech.28.4.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gram L. F., Kovács I., Pedersen A. Oral og intrauterin antikonception. Ugeskr Laeger. 1976 May 3;138(19):1133–1139. [PubMed] [Google Scholar]
  14. Harmsen P., Berglund G., Larsson O., Tibblin G., Wilhelmsen L. Stroke registration in Göteborg, Sweden, 1970-75. Incidence and fatality rates. Acta Med Scand. 1979;206(5):337–344. doi: 10.1111/j.0954-6820.1979.tb13524.x. [DOI] [PubMed] [Google Scholar]
  15. Herman B., Schmitz P. I., Leyten A. C., Van Luijk J. H., Frenken C. W., Op De Coul A. A., Schulte B. P. Multivariate logistic analysis of risk factors for stroke in Tilburg, The Netherlands. Am J Epidemiol. 1983 Oct;118(4):514–525. doi: 10.1093/oxfordjournals.aje.a113657. [DOI] [PubMed] [Google Scholar]
  16. Inman W. H., Vessey M. P. Investigation of deaths from pulmonary, coronary, and cerebral thrombosis and embolism in women of child-bearing age. Br Med J. 1968 Apr 27;2(5599):193–199. doi: 10.1136/bmj.2.5599.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jick H., Porter J., Rothman K. J. Oral contraceptives and nonfatal stroke in healthy young women. Ann Intern Med. 1978 Jul;89(1):58–60. doi: 10.7326/0003-4819-89-1-58. [DOI] [PubMed] [Google Scholar]
  18. Kay C. R. The Royal College of General Practitioners' Oral Contraception Study: some recent observations. Clin Obstet Gynaecol. 1984 Dec;11(3):759–786. [PubMed] [Google Scholar]
  19. Lidegaard O. Cerebrovascular deaths before and after the appearance of oral contraceptives. Acta Neurol Scand. 1987 Jun;75(6):427–433. doi: 10.1111/j.1600-0404.1987.tb05473.x. [DOI] [PubMed] [Google Scholar]
  20. Lidegaard O., Soe M., Andersen M. V. Cerebral thromboembolism among young women and men in Denmark 1977-1982. Stroke. 1986 Jul-Aug;17(4):670–675. doi: 10.1161/01.str.17.4.670. [DOI] [PubMed] [Google Scholar]
  21. Lidegaard O. Tromboemboliske attakker i centralnervesystemet og p-piller. Ugeskr Laeger. 1982 Sep 20;144(38):2769–2772. [PubMed] [Google Scholar]
  22. Markush R. E., Turner S. L. Epidemiology of exogenous estrogens. HSMHA Health Rep. 1971 Jan;86(1):74–86. [PMC free article] [PubMed] [Google Scholar]
  23. Mettinger K. L., Söderström C. E., Allander E. Epidemiology of acute cerebrovascular disease before the age of 55 in the Stockholm County 1973-77: I. Incidence and mortality rates. Stroke. 1984 Sep-Oct;15(5):795–801. doi: 10.1161/01.str.15.5.795. [DOI] [PubMed] [Google Scholar]
  24. Mettinger K. L., Söderström C. E., Neiman J. Stroke before 55 years of age at Karolinska Hospital 1973-77. A study of 399 well-defined cases. Risk indicators and etiological considerations. Acta Neurol Scand. 1984 Dec;70(6):415–422. doi: 10.1111/j.1600-0404.1984.tb00846.x. [DOI] [PubMed] [Google Scholar]
  25. Mishell D. R., Jr Correcting misconceptions about oral contraceptives. Am J Obstet Gynecol. 1989 Nov;161(5):1385–1389. doi: 10.1016/0002-9378(89)90700-x. [DOI] [PubMed] [Google Scholar]
  26. Nomura A., Comstock G. W., Kuller L., Tonascia J. A. Cigarette smoking and strokes. Stroke. 1974 Jul-Aug;5(4):483–486. doi: 10.1161/01.str.5.4.483. [DOI] [PubMed] [Google Scholar]
  27. Oleckno W. A. The risk of stroke in young adults: an analysis of the contribution of cigarette smoking and alcohol consumption. Public Health. 1988 Jan;102(1):45–55. doi: 10.1016/s0033-3506(88)80009-x. [DOI] [PubMed] [Google Scholar]
  28. Realini J. P., Goldzieher J. W. Oral contraceptives and cardiovascular disease: a critique of the epidemiologic studies. Am J Obstet Gynecol. 1985 Jul 15;152(6 Pt 2):729–798. doi: 10.1016/s0002-9378(85)80001-6. [DOI] [PubMed] [Google Scholar]
  29. Salonen J. T., Puska P., Tuomilehto J., Homan K. Relation of blood pressure, serum lipids, and smoking to the risk of cerebral stroke. A longitudinal study in Eastern Finland. Stroke. 1982 May-Jun;13(3):327–333. doi: 10.1161/01.str.13.3.327. [DOI] [PubMed] [Google Scholar]
  30. Sartwell P. E., Masi A. T., Arthes F. G., Greene G. R., Smith H. E. Thromboembolism and oral contraceptives: an epidemiologic case-control study. Am J Epidemiol. 1969 Nov;90(5):365–380. doi: 10.1093/oxfordjournals.aje.a121082. [DOI] [PubMed] [Google Scholar]
  31. Stolley P. D., Strom B. L., Sartwell P. E. Oral contraceptives and vascular disease. Epidemiol Rev. 1989;11:241–243. doi: 10.1093/oxfordjournals.epirev.a036041. [DOI] [PubMed] [Google Scholar]
  32. Stolley P. D., Tonascia J. A., Sartwell P. E., Tockman M. S., Tonascia S., Rutledge A., Schinnar R. Agreement rates between oral contraceptive users and prescribers in relation to drug use histories. Am J Epidemiol. 1978 Mar;107(3):226–235. doi: 10.1093/oxfordjournals.aje.a112529. [DOI] [PubMed] [Google Scholar]
  33. Thorogood M., Mann J., Murphy M., Vessey M. Fatal stroke and use of oral contraceptives: findings from a case-control study. Am J Epidemiol. 1992 Jul 1;136(1):35–45. doi: 10.1093/oxfordjournals.aje.a116418. [DOI] [PubMed] [Google Scholar]
  34. Vessey M. P., Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J. 1969 Jun 14;2(5658):651–657. doi: 10.1136/bmj.2.5658.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vessey M. P., Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J. 1968 Apr 27;2(5599):199–205. doi: 10.1136/bmj.2.5599.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vessey M. P., Lawless M., Yeates D. Oral contraceptives and stroke: findings in a large prospective study. Br Med J (Clin Res Ed) 1984 Sep 1;289(6444):530–531. doi: 10.1136/bmj.289.6444.530-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wiseman R. A. Absence of correlation between oral contraceptive usage and cardiovascular mortality. Int J Fertil. 1984;29(4):198–208. [PubMed] [Google Scholar]
  38. Wolf P. A., D'Agostino R. B., Kannel W. B., Bonita R., Belanger A. J. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA. 1988 Feb 19;259(7):1025–1029. [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES