Section of Epidemiology and Public Health, University G. d'Annunzio of Chieti, Chieti, Italy.
Drug Saf. 2012 Mar 1;35(3):191-205. doi: 10.2165/11598050-000000000-00000.
An association between oral contraceptive (OC) use and venous thromboembolism (VTE) has long been recognized. However, no summary estimates of the increase in VTE risk associated with OC use have been available since 1995, and no meta-analyses have evaluated the VTE risk of new preparations containing drospirenone.
The aim of the study was to carry out a meta-analysis to summarize existing evidence on the association between venous VTE and OC use, and to investigate how such an association may vary according to the type of OC, OC user characteristics, study characteristics and biases.
Relevant cohort or case-control studies were searched in MEDLINE and other electronic databases up to May 2010, with no language restriction. Data were combined using a generic inverse-variance approach. Meta-regression in addition to stratification was used to explore potential predictors of the summary estimate of risk.
Sixteen cohort and 39 case-control studies were included in at least one comparison. Overall, the odds ratio (OR) of OC users versus non-users was 3.41 (95% CI 2.98, 3.92). This estimate was based upon nine cohort studies evaluating approximately 12 000 000 person-years, and 23 case-control studies including approximately 45 000 women. VTE risk for OC users was significantly lower in studies evaluating 'all VTE cases' than in those evaluating 'idiopathic VTE only' (OR 3.09 and 4.94, respectively). Among the carriers of genetic mutations G20210A and Factor V Leiden (FVL), OC users showed a significantly increased VTE risk compared with non-users (OR 1.63; 95% CI 1.01, 2.65, and OR 1.80; 95% CI 1.20, 2.71, respectively). When the newest OCs containing drospirenone were compared with non-drospirenone-containing OCs (except those containing levonorgestrel only), VTE risk did not significantly increase (OR 1.13; 95% CI 0.94, 1.35).
This meta-analysis confirms that OC use significantly increases VTE risk. The strength of this association, however, varies according to the generation of OC, type of outcome and presence of a genetic mutation, with ORs ranging from 3 to 5.
长期以来，人们一直认识到口服避孕药（OC）的使用与静脉血栓栓塞症（VTE）之间存在关联。然而，自 1995 年以来，一直没有关于与 OC 使用相关的 VTE 风险增加的汇总估计值，也没有荟萃分析评估含有屈螺酮的新制剂的 VTE 风险。
本研究旨在进行荟萃分析，以总结现有的关于静脉 VTE 与 OC 使用之间关联的证据，并研究这种关联可能如何根据 OC 的类型、OC 用户的特征、研究特征和偏倚而变化。
在 MEDLINE 和其他电子数据库中检索了截止到 2010 年 5 月的相关队列或病例对照研究，无语言限制。使用通用逆方差方法合并数据。除分层外，还使用荟萃回归来探索风险汇总估计值的潜在预测因素。
纳入了至少一项比较的 16 项队列研究和 39 项病例对照研究。总体而言，OC 使用者与非使用者的比值比（OR）为 3.41（95%置信区间 2.98，3.92）。该估计值基于九项队列研究评估了约 1200 万个人年，以及 23 项病例对照研究评估了约 45000 名女性。在评估“所有 VTE 病例”的研究中，OC 使用者的 VTE 风险明显低于仅评估“特发性 VTE”的研究（OR 分别为 3.09 和 4.94）。在携带基因突变 G20210A 和因子 V 莱顿（FVL）的携带者中，OC 使用者的 VTE 风险明显高于非使用者（OR 分别为 1.63；95%置信区间 1.01，2.65 和 OR 1.80；95%置信区间 1.20，2.71）。当比较含有屈螺酮的最新 OC 与不含屈螺酮的 OC（仅含有左炔诺孕酮的 OC 除外）时，VTE 风险没有明显增加（OR 1.13；95%置信区间 0.94，1.35）。
这项荟萃分析证实 OC 的使用显著增加了 VTE 的风险。然而，这种关联的强度因 OC 的代际、结局类型和基因突变的存在而有所不同，OR 值范围为 3 至 5。
