Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel

doi:10.1016/j.contraception.2006.02.002

Contraception

Volume 73, Issue 6, June 2006, Pages 566-570

https://doi.org/10.1016/j.contraception.2006.02.002 Get rights and content

Abstract

Context

Previous studies have reported that users of the “third-generation” oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking.

Objective

The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel.

Design, Setting and Participants

Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 μg of ethinyl estradiol (EE), desogestrel with 30 μg of EE or levonorgestrel with 30 μg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs.

Results

Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8–1.6] and 1.7 (95% CI, 1.1–2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5–36.5), 53.5 (95% CI, 42.9–66.0) and 27.1 (95% CI, 21.1–34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8–1.5) and 2.0 (95% CI, 1.4–2.7), respectively.

Conclusions

The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.

Introduction

Three reports published in Lancet in 1995 found an approximately twofold increased risk of venous thromboembolism (VTE) for oral contraceptives (OCs) containing either desogestrel or gestodene, compared to OCs containing levonorgestrel [1], [2], [3]. Norgestimate-containing OCs, which are not commonly used in the UK, are among the most commonly prescribed OCs in the Unites States. Reliable information on the effects of norgestimate-containing OCs on the risk for VTE has not been published since most of the earlier studies on the risk of VTE among users of OCs were conducted in Europe and other countries where norgestimate-containing OCs are uncommonly prescribed and information was therefore limited. The question remains whether the progestin norgestimate is more similar to the levonorgestrel-containing “second-generation” or to the desogestrel-containing “third-generation” OCs with respect to its effect on the risk of VTE [4]. Since “third-generation” OCs have been reported to increase the risk of VTE, and because norgestimate-containing contraceptives are widely prescribed in the United States, we conducted a study to compare the risk of nonfatal VTE in users of norgestimate-containing OCs with 35 μg of ethinyl estradiol (EE) and, separately, desogestrel-containing OCs with 30 μg of EE (a “third-generation” pill used in the United States) to the risk of nonfatal VTE in users of levonorgestrel-containing OCs with 30 μg of EE. This is the first study that we know of to evaluate the effects on VTE risk of norgestimate- and desogestrel-containing OCs in the United States.

Section snippets

Data resource

Data for this study were derived from the PharMetrics database. PharMetrics is a United States-based ongoing longitudinal database with information on about 55 million people starting as early as 1995. The database is made up of data contributed by managed care plans throughout the United States, and it contains information on paid claims for pharmaceutical agents, medical diagnoses and procedures as well as demographic information on all subjects. Demographic information such as patient's year

Results

Approximately 1.3 million women in the PharMetrics database filled at least one prescription for a study OC during the study period. From this population, we identified 281 cases of idiopathic VTE and 1055 controls (women without VTE) matched by year of birth and index date. Characteristics of the cases and controls are listed in Table 1. The risk of VTE increased with increasing age, and cases were significantly more likely than controls to have diabetes, menstrual disorders and back pain.

Discussion

The results of this study indicate that the risk of nonfatal VTE is similar in users of norgestimate- and levonorgestrel-containing OCs and significantly higher among current users of desogestrel-containing OCs compared to current users of the levonorgestrel-containing OCs [OR, 1.7 (95% CI, 1.1–2.4); IRR, 2.0 (95% CI, 1.4–2.7)], and these findings are consistent with the results of earlier studies [1], [2], [3], [4], [5]. As in prior studies, age and calendar time were closely controlled, that

Acknowledgments

This study was funded by Johnson and Johnson and conducted by the Boston Collaborative Drug Surveillance Program of Boston University Medical Center.

S. Russmann is supported by a Merck Sharp and Dohme International Fellowship in Clinical Pharmacology.

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Les événements vasculaires veineux ou artériels constituent le principal effet délétère de l’utilisation des contraceptions hormonales combinées (CHC). Même si leur composition a nettement évolué, ce risque persiste avec les CHC les plus récentes. Si le risque vasculaire des CHC contenant 50 μg d’EE est nettement plus important que celui des CHC contenant moins de 50 μg, il n’y a pas de preuve que les CHC contenant soit 30 soit 20 μg d’EE induisent des risques veineux différents. Les CHC contenant du gestodène, du désogestrel, de la drospirénone ou de l’acétate de cyprotérone sont associés à un risque de thrombose veineuse plus élevé comparativement aux CHC contenant du lévonorgestrel. Les CHC contenant du norgestimate sont associés à un risque de thrombose veineuse similaire à celui des CHC contenant du lévonorgestrel. Le risque veineux des voies d’administration non orales des CHC semble équivalent au risque des CHC contenant du gestodène ou du désogestrel, mais ce résultat est basé sur un faible nombre d’études épidémiologiques. Dans ce contexte, avant de prescrire une CHC, il est important de déterminer l’ensemble des facteurs de risque vasculaires. Les antécédents familiaux qu’ils soient artériels ou veineux doivent être systématiquement recherchés avant toute prescription de CHC. Toutes les CHC sont contre-indiqués chez les femmes porteuses d’une thrombophilie biologique, chez les jeunes femmes ayant des antécédents familiaux vasculaires (artériel ou veineux) au premier degré survenus à un âge jeune (moins de 50 ans) ainsi que les femmes souffrant de migraines avec aura ou combinant plusieurs facteurs de risque vasculaire. Les contraceptions progestatives ne sont pas associées au risque vasculaire (artériel ou veineux) en dehors de l’acétate de médroxyprogestérone qui augmente le risque de thrombose veineuse. Chez une femme à haut risque vasculaire souhaitant une contraception hormonale, les contraceptions progestatives seules en dehors de l’acétate de médroxyprogestérone injectable peuvent être prescrites.
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Original research articleRisk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel

Abstract

Context

Objective

Design, Setting and Participants

Results

Conclusions

Introduction

Section snippets

Data resource

Results

Discussion

Acknowledgments

Lancet

Lancet

Lancet

Lancet

Contraception

Original research article
Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel