Semin Vasc Med 2003; 03(1): 001-002
DOI: 10.1055/s-2003-38336
PREFACE

Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Oral Contraceptives, Pregnancy, Hormone Replacement, and Thrombosis

Jan Rosing, F. Eric Preston
  • Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; and Royal Hallamshire Hospital, Sheffield, United Kingdom
Further Information

Publication History

Publication Date:
27 March 2003 (online)

Deep venous thrombosis (DVT) and its sequela, pulmonary embolism, is a leading cause of cardiovascular death in developed countries. This disorder commonly manifests as DVT of the leg or, if embolization occurs, as a pulmonary embolism. Occasionally, thrombosis may develop at other locations, such as the arm, cerebral veins, or in veins in the retina or pelvic region. Annually, venous thrombosis occurs in 1 in 1000 individuals. However, the incidence of venous thrombosis is strongly dependent on age and varies from 1 per 100,000 people per year in childhood, rising sharply after middle age to about 1 per 100 individuals per year.

The occurrence of thrombosis is not just a matter of chance, but often can be associated with the presence of one or more risk factors, which can be either of acquired or of genetic origin. Acquired risk factors of venous thrombosis include malignancy, antiphospholipid antibodies, immobilization, surgery, trauma, pregnancy and the use of oral contraceptives (OC), or hormone replacement therapy (HRT). At present, a number of well-defined genetic risk factors for VT are known, which together can only partly explain the occurrence of thrombosis in thrombophilic families. Due to the development of DNA sequencing techniques, the number of known hereditary risk factors for venous thrombosis has been steadily increasing during the last two decennia. The major genetic risk factors are deficiencies in the anticoagulant proteins antithrombin, protein C, and protein S; resistance to activated protein C (APC), which in the majority of the cases is due to a mutation in coagulation factor V, called factor VLeiden; and a mutation in the prothrombin gene that is associated with increased plasma levels of prothrombin. Recent epidemiological studies indicated elevated plasma concentrations of other coagulation factors (e.g., factor VIII, factor IX, and factor XI) are also risk factors for venous thrombosis. Although in some studies a familial clustering was observed, as yet no mutations responsible for high coagulation factor levels other than prothrombin have been identified.

In a large number of individuals who carry a thrombotic mutation, or who are exposed to an acquired risk factor, venous thrombosis will not manifest itself. This is due to the fact that thrombosis appears to be a multicausal disease that mainly affects people in whom two or more hereditary and/or acquired risk factors occur simultaneously.

Women experience a number of gender-specific risk factors for venous thromboembolic disease, including pregnancy, OC use, and HRT. The fact that soon after the introduction of OC in the early sixties, the first case reports on thrombotic complications in pill users appeared in the literature indicates that changes in the sex steroid hormones in women are directly responsible for the development of venous thrombosis. Since then efforts have been made to establish the venous thrombotic risk associated with the use of different hormone preparations in various groups of users, and to develop hormone preparations (OC and HRT) that are accompanied by a lower risk of venous thrombosis. In addition, attempts are being made to provide a biological explanation for hormone-induced venous thrombotic risk in women. With respect to OC, the estrogen content has been gradually reduced and new progestagens have been introduced with the aim of reducing the thrombogenicity of the pills. Despite numerous reports on the effects of pregnancy, OC, and HRT on a wide variety of hemostatic parameters, a clear picture of a possible causal relationship between changes in hemostatic variables and the occurrence of venous thrombosis has failed to emerge.

However, in 1995 a number of epidemiological studies were published that indicated that women who use OC containing the so-called third generation progestagens desogestrel or gestodene are exposed to approximately a two-fold higher risk for venous thrombosis than users of the older second generation pill that contains levonorgestrel as progestagen. These reports provoked new studies on the effects of second and third generation OC on hemostatic parameters in an attempt to find a biological explanation for the difference in thrombotic risks associated with the use of these two kinds of pills. At the same time, more information became available with respect to the mechanistic basis of venous thrombosis in general, and recent coagulation studies have provided a better understanding of the etiology of thrombosis occurring during pregnancy, HRT, and OC use.

The present issue of Seminars in Vascular Medicine deals with the topics discussed in this preface. The latest insights into the risk factors for venous thrombosis in general, and knowledge of thrombotic risks associated with the use of old and new hormone preparations (OC and HRT)-in combination with recent studies on the effects of these preparations on the hemostatic system-will ultimately lead to hormone prescriptions tailored to the individual woman, and will provide the basis for the development of new kinds of OC and HRT that expose women to a lower risk of venous thrombosis.

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