Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

Birthe Søgaard Andersen; Jørn Olsen; Gunnar Lauge Nielsen; Flemming Hald Steffensen; Henrik Toft Sørensen; John Baech; Henrik Gregersen

doi:10.1055/s-0037-1614213

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(01): 28-31
DOI: 10.1055/s-0037-1614213

Review Article

Schattauer GmbH

Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

Birthe Søgaard Andersen

¹From The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark

²Department of Internal Medicine M, Aalborg Hospital, Aalborg, Denmark

,

Jørn Olsen

¹From The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark

,

Gunnar Lauge Nielsen

¹From The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark

²Department of Internal Medicine M, Aalborg Hospital, Aalborg, Denmark

,

Flemming Hald Steffensen

¹From The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark

²Department of Internal Medicine M, Aalborg Hospital, Aalborg, Denmark

,

Henrik Toft Sørensen

¹From The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus, Denmark

³Department of Internal Medicine V, Aarhus University Hospital, Aarhus, Denmark

,

John Baech

⁴Department of Clinical Immunology, Aalborg Hospital, Aalborg, Denmark

,

Henrik Gregersen

⁴Department of Clinical Immunology, Aalborg Hospital, Aalborg, Denmark

› Author Affiliations

Abstract

Summary

Third generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour.

We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency.

Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively.

It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.

Full Text

References

References
1 World Health Organization Collaborative Study of Cardio vascular Disease and Steroid Hormone Contraception.. Venous thromboembolic disease and combined oral contraceptives: results of an international multicentre case-control study.. Lancet 1995; 346: 1575-81.
2 World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease.. Lancet 1995; 346: 1582-8.
3 Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and non-fatal venous thromboembolism in women using oral contraceptives with differing progestagen components.. Lancet 1995; 346: 1589-93.
4 Spitzer WO, Lewis MA, Heinemann LAJ, Thorogood M, Macrae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study.. BMJ 1995; 312: 83-8.
5 Committee on Safety of Medicines.. Combined oral contraceptives and thromboembolism.. London: CSM; 1995
6 Robinson GE. Low-dose combined oral contraceptives.. Br J Obstet Gynaecol 1994; 101: 1036-42.
7 Speroff L, De Cherney A. Evaluation of a new generation of oral contraceptives.. Obstet Gynecol 1993; 81: 1034-47.
8 Fotherby K, Caldwell ADS. New progestogens in oral contraception.. Contraception 1994; 49: 1-33.
9 Lewis MA, Heinemann LAJ, MacRae KD, Bruppacher R, Spitzer WO. The increased risk of venous thromboembolism and the use of third generation progesterons: roles of bias in observational research.. Contraception 1996; 54: 5-13.
10 Westhoff CL. Oral contraceptives and venous thromboembolism: Should epidemiologic associations drive clinical decision making?. Contraception 1996; 54: 1-3.
11 Bloemenkamp KWM, Rosendaal FR, Helmerhorst FM, Büller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progesterone.. Lancet 1995; 346: 1593-7.
12 Vandenbroucke JP, Koster T, Briët E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation.. Lancet 1994; 344: 1453-7.
13 Pabinger I. Schneider B and the GTH Study Group on Natural Inhibitors.. Thrombosis risk of women with hereditary antithrombin III-, protein C- and protein S-deficiency taking oral contraceptive medication.. Thromb Haemost 1994; 71: 548-52.
14 Sørensen HT. Regional administrative health registries as a resource in clinical epidemiology.. A study of options, strengths, limitations and data quality provided with examples of use. Aarhus, 1996. Dissertation.
15 International Center of Disease Classification. Eighth Revised edition Copenhagen: Sundhedsstyrelsen; 1977
16 International Statistical Classification of Diseases and Health Related Problems. Tenth Revised edition Copenhagen: Sundhedsstyrelsen; 1993
17 Preda L, Tripodi A, Valsecchi C, Lombardi A, Finotti E, Mannucci PM. A prothrombin time-based functional assay of protein S.. Thromb Res 1990; 60: 19-32.
18 Breslow NE, Day NE. Statistical methods in cancer research I: analysis of case-control studies.. Lyon: International Agency for Research on Cancer; 1980
19 Vandenbroucke JP, Rosendaal FR. End of the line for “third-generation-pill” controversy?. Lancet 1997; 349: 1113-4.
20 Lidegaard Ø. Oral contraceptives and cerebral thromboembolism. An epidemiological approach.. Copenhagen: 1996. Dissertation.
21 Stubblefield PG. The effects on hemostasis of oral contraceptives containing desogestrel.. Am J Obstet Gynecol 1993; 168: 1047-52.
22 Daly L, Bonnar J. Comparative studies of 30 g ethinyl estradiol combined with gestodene and desogestrel on blood coagulation, fibrinolysis, and platelets.. Am J Obstet Gynecol 1990; 163: 430-7.