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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.

Objectives: The aim of this study was to assess preferential prescribing of OC according to different thrombotic risk factors., Material and Methods: The control group in an ongoing Danish case-control study on stroke and OCs collected in 1994 and 1995 underwent a control-only analysis concerning the occurrence of thrombotic risk factors among users of different types of OC. Specific attention was given to differences between OCs with second and third generation progestagens. The association between specific risk factors and the pill types was assessed crude and after multivariate analysis with confounder control for age and other risk factors, in order to identify risk factors, which after these corrections still had a significant confounding influence on the prescribing of OC., Results: Users of OCs with third generation progestagens had a significantly higher proportion of familial thrombotic disposition (23.1%) than users of OCs with second generation progestagens (7.1%) (p = 0.01). After correction for age and other risk factors this difference was still highly significant (p = 0.002). Among users of third generation pills the proportion of short time users (< 1 year) (22.4%) was significantly higher than the per cent among users of OCs with second generation progestagens (5.5%) (p < 0.001). This difference was still significant after correction for age and other risk factors (p < 0.001). Smoking, years of schooling, migraine, and body mass index did not differ significantly between the two pill groups., Conclusion: In Denmark, women with familial thrombotic disposition are four times more likely being prescribed OCs with third versus second generation progestagens compared with women without such a disposition. At the same time users of OCs with third generation progestagens include significantly more short time users than users of OCs with second generation progestagens. For thrombotic diseases where familial disposition or duration of use of OCs play a role for the pill-associated risk, these differences may significantly influence the thrombotic risk measures in case-control studies and non-randomized cohort studies unless confounder control is conducted for this selection.

New epidemiological studies have demonstrated a higher risk of venous thromboembolism among users of oral contraceptives (OCs) with third-generation progestogens desogestrel or gestodene compared with users of OCs with second-generation progestogens levonorgestrel or norgestrel. As the absolute risk of venous thromboembolism among users of OCs in general is lower in the new studies than in previously published studies, and as several important potential confounders are not controlled for in the new studies, the real difference in risk of venous thromboembolism between users of third- compared with second-generation products may be smaller than indicated in these new studies. At the same time, the risk of myocardial infarction may be smaller among users of third- compared with users of second-generation products. Until further epidemiological data emerge, it is therefore difficult to make general recommendations other than to use OCs with a low estrogen dose, and to make individual recommendations based on age, individual wish, and individual risk factors.

The use of oral contraceptives (OC) has been correlated to several diseases, primarily thromboembolic conditions. Whether these correlations represent a causal relationship or a mere statistical correlation based on other variables, depends on whether users of OC differ in other respects from women in fertile age not using OC. We interviewed 519 Danish women, 15-45 years old and selected at random, concerning present and past use of OC, age, occupation, years of schooling, marital status, income, smoking habits, urbanization, and their opinion on the postulated thrombotic risk among users of OC. The data were analysed by methods for multivariate contingency tables. Opinions on the thrombotic risk, age, smoking habits and, to a lesser degree, regarding income, were directly correlated to the oral contraceptive use. There was no direct interaction between the use of OC and the other variables. Users of OC were younger and smoked more than the non-users and were of the opinion that the use of OC implied only minor thrombotic risk, or none at all.