Elsevier

Contraception

Volume 70, Issue 6, December 2004, Pages 437-441
Contraception

Original research article
Progestogen-only contraception in women at high risk of venous thromboembolism

https://doi.org/10.1016/j.contraception.2004.07.009Get rights and content

Abstract

The objective of the study was to evaluate the venous impact of a progestogen-only contraception on women at high risk of venous thromboembolism (VTE). In this retrospective cohort study, 204 consecutive women at high risk of VTE were recruited between January 1992 and June 1997 and were prospectively followed. Women using chlormadinone acetate (CMA) at antigonadotropic doses (n=102) were matched by age and date of referral and history of venous thrombosis with women who had no hormonal contraception (n=102). During follow-up (mean of 33 months), nine episodes of VTE were observed: three in women receiving CMA and six in nontreated women. Using the Cox model to adjust for confounding variables such as age, thrombophilia and body mass index, the relative risk of VTE associated with the use of CMA was not significant [relative risk: 0.8 (0.2–3.9)]. These reassuring results need to be confirmed in other prospective studies.

Introduction

Combined oral contraception (COC) with ethinyl estradiol (EE) and a progestogen is one of the most common risk factors of venous thrombosis among young women, and it is associated with an approximate fourfold risk in recent studies [1], [2]. However, it is now recognized that venous thrombosis is frequently multifactorial and sometimes multigenic. Different risk factors such as age, surgery and immobilization (plaster cast; prolonged journeys in plane, bus or car) may be present. In addition, some women are at higher risk when they have had a previous thrombosis or when they have genetic or acquired predisposition to venous thrombosis: antiphospholipid syndrome with circulating anticoagulant or hereditary thrombophilia as a result of deficiency in antithrombin (AT), protein C (PC) or protein S (PS), or mutations of factor V (FV Leiden) or of prothrombin (factor II [FII] 20210A). Combined thrombophilias may even be present in the same patient.

Small doses of 19-nor-testosterone derivatives administered every day are a possible means of contraception, but side effects such as bleeding, amenorrhea, spotting and mastodynia are frequently observed. In France, other progestogens such as the 17α-hydroxyprogesterone derivatives (pregnane) and the 19-nor-progesterone derivatives (norpregnane) are used at antigonadotropic doses [3]. Chlormadinone acetate (CMA), a 17α-hydroxyprogesterone derivative, was initially used at high doses for contraception in diabetic women and women with renal transplantation and subsequently in women at risk of venous thrombosis [4], [5], [6]. This compound was not shown to induce deleterious metabolic or hemostatic effects [5].

We have conducted a retrospective cohort study to evaluate the venous impact of CMA administered at antigonadotropic doses on women at high risk of venous thromboembolism (VTE).

Section snippets

Methods

We included 204 consecutive women at high risk of VTE: 102 who received oral contraception (OC) with CMA and 102 matched women who did not receive oral contraception.

Results

General characteristics of the women are presented in Table 1. The mean age upon inclusion was 29.7 years (range: 15–50). The two groups of women (CMA-treated and nontreated) did not differ significantly, except for thrombophilia (p=.05); thus, the Cox model was adjusted on this parameter. Most of the women were included because they had a personal history of VTE (70% in each group) associated with thrombophilia, in 24% and 26% of the CMA-treated women and nontreated women, respectively.

Discussion

All 204 women of this study were at high risk of VTE upon inclusion in the study because of a previous episode in 142 (70%) or thrombophilia in 102 (50%). Combined oral contraception was associated with the previous episode in 100 women. Any COC was considered as contraindicated in this series of women, although the second-generation progestogens and the low doses of 20 μg EE have recently been shown to be associated with a lower risk of VTE [8], [9]. The administration of COC together with an

Conclusion

Progestogen-only contraception with CMA is not associated with an increased risk of VTE in this series of high-risk women. The results suggest that it may be used in women who have contraindication for COC. Chlormadinone acetate, as with other progestogen-only contraceptives, is not an every-woman contraceptive because side effects such as amenorrhea or spotting may be observed. However, CMA makes OC possible in women in whom COC is contraindicated and in whom pregnancy is also associated with

Acknowledgment

We thank all referring physicians, especially gynecologists of the Association Médicale des Gynécologues et Obstétriciens de Paris (AMGOP).

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