Oral contraceptives and venous thromboembolism. A case-control study.

To assess the influence of oral contraceptives (OC) on the risk for venous thromboembolism (VTE) in young women, a 5-year case-control study including all women 15-44 years old suffering a first deep venous thrombosis or a first pulmonary embolism from all Danish hospitals, along with 1200 control subjects during the period 1994-1995, was conducted. Of 586 patient and 1200 control subject questionnaires sent out, 523 patient (89.2%) and 1074 control (89.5%) questionnaires were returned with an agreement to participate. After exclusion of women with nonvalid diagnoses, women who were pregnant, and women with previous VTE or acute myocardial infarction (AMI), 375 patients and 1041 control subjects were available for analysis. Potential tested confounders included: body mass index, length of OC use, family history of VTE, AMI, or stroke, smoking habits, coagulopathies, diabetes, years of schooling, certainty of diagnosis, previous births, and treated hypertension during any pregnancy. A multivariate analysis was performed. Estrogen dose had no influence on the risk for VTE. The risk for VTE among current users of OC was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: < 1 year; 5.1 (3.1-8.5); 1-5 years; 2.5 (1.6-4.1); and > 5 years; 2.1 (1.5-3.1), all compared with those for nonusers of OC. This trend was still significant after adjustment for progestin types. Without adjustment for duration of use, current users of OC with second generation (levonorgestrel or norgestimate) and third generation (desogestrel or gestodene) progestins had OR of 1.8 (1.1-2.9) and 3.2 (2.3-4.4), respectively. After correction for duration of use, however, no significant differences were found between users of OC with different types of progestins. In conclusion, OC increase the risk for VTE significantly. The risk among current users of OC is primarily influenced by duration of use. No difference in risk was found according to estrogen dose, and the difference in risk between different types of progestins was not statistically significant after adjustment for duration of use.

[1]  Clyne,et al.  Investigation of relation between use of oral contraceptives and thromboembolic disease. , 1968, British medical journal.

[2]  H. Hemker,et al.  Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second‐ and third‐generation oral contraceptives , 1997, British journal of haematology.

[3]  I. Milsom,et al.  Oral contraceptives and thrombotic diseases: impact of new epidemiological studies. , 1996, Contraception.

[4]  W. Spitzer,et al.  Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study , 1996, BMJ.

[5]  A. Stergachis,et al.  Oral Contraceptives and Nonfatal Vascular Disease—Recent Experience , 1982, Obstetrics and gynecology.

[6]  F. Lundin,et al.  Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. , 1991, American journal of epidemiology.

[7]  W. Spitzer,et al.  First-time use of newer oral contraceptives and the risk of venous thromboembolism. , 1997, Contraception.

[8]  P M Layde,et al.  Agreement between women's histories of oral contraceptive use and physician records. , 1983, International journal of epidemiology.

[9]  M. Vessey,et al.  Accuracy of recall of histories of oral contraceptive use , 1974, British journal of preventive & social medicine.

[10]  D. Mant,et al.  Oral contraceptives and venous thromboembolism: findings in a large prospective study. , 1986, British medical journal.

[11]  P. Stolley,et al.  Agreement rates between oral contraceptive users and prescribers in relation to drug use histories. , 1978, American journal of epidemiology.

[12]  C. Kay ORAL CONTRACEPTIVES AND VENOUS THROMBOSIS , 1975, The Lancet.

[13]  D. Kennedy,et al.  Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism. , 1990, International journal of epidemiology.

[14]  T. Farley,et al.  Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. , 1995, Lancet.

[15]  T. Farley,et al.  Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease , 1995 .

[16]  Ø. Lidegaard,et al.  Thrombotic diseases in young women and the influence of oral contraceptives. , 1998, American journal of obstetrics and gynecology.

[17]  J. Vandenbroucke,et al.  Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen , 1995, The Lancet.

[18]  Svend Kreiner,et al.  Analysis of Multidimensional Contingency Tables by Exact Conditional Tests: Techniques and Strategies , 1987 .

[19]  Cerebral thrombosis and oral contraceptives. A case-control study. , 1998 .

[20]  Ø. Lidegaard The influence of thrombotic risk factors when oral contraceptives are prescribed a control‐only study , 1997 .

[21]  J. N. R. Jeffers,et al.  Graphical Models in Applied Multivariate Statistics. , 1990 .

[22]  A. Coulter,et al.  The ability of women to recall their oral contraceptive histories. , 1986, Contraception.

[23]  J. Vandenbroucke,et al.  Safety of combined oral contraceptive pills , 1996, The Lancet.

[24]  K D MacRae,et al.  The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. The Transnational Research Group on Oral Contraceptives and the Health of Young Women. , 1996, Contraception.

[25]  M. Thorogood,et al.  Risk factors for fatal venous thromboembolism in young women: a case-control study. , 1992, International journal of epidemiology.

[26]  H. Jick,et al.  Risk of idiopathic cardiovascular death and rionfatal venous thromboembolism in women using oral contraceptives with differing progestagen components , 1995, The Lancet.

[27]  N. Wermuth,et al.  Graphical and recursive models for contingency tables , 1983 .

[28]  K. Overgaard,et al.  [Venous thromboembolic disease and oral contraceptives]. , 1986, Ugeskrift for laeger.

[29]  R. Farmer,et al.  Population-based study of risk of venous thromboembolism associated with various oral contraceptives , 1997, The Lancet.