Population-based study of risk of venous thromboembolism associated with various oral contraceptives
Population-based study of risk of venous thromboembolism associated with various oral contraceptives
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DOI：
10.1016/s0140-6736(96)07496-x
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发表时间：
1997-01-11
期刊：
影响因子：
168.9
通讯作者：
Hambleton, IR
中科院分区：
文献类型：
--
作者：
Farmer, RDT;Lawrenson, RA;Hambleton, IR
背景自1995年12月以来发表的4项研究报告称，使用含第三代孕激素孕二烯酮或去氧孕烯的口服避孕药（OC）的妇女静脉血栓栓塞（VTE）的发生率高于使用含第二代孕激素的OC的妇女。然而，这些研究设计中的混杂和偏倚可能会影响研究结果。我们的研究的目的是重新审视与不同的研究设计和分析，以避免一些偏见和混淆的早期study.Methods的VTE和OC使用的风险之间的关联，我们使用的计算机记录的患者从143个一般的做法在英国。这项研究是基于1941年至1981年间出生的约54万名女性的医疗记录。所有在研究期间有深静脉血栓形成、静脉血栓形成（未另行说明）或肺栓塞的诊断记录并接受抗凝剂治疗的女性均被确定为潜在的VTE病例。我们进行了一项队列分析，以估计和比较主要OC制剂使用者的VTE发生率，并进行了一项巢式病例对照研究，以计算在调整潜在混杂因素后，与使用不同类型OC相关的VTE的比值比。在病例对照研究中，我们将病例与对照组按确切的出生年份、实践和目前使用的OC进行匹配。我们使用了一个多元逻辑回归模型，包括体重指数，周期数，在OC类型的变化规定在3个月内的事件，以前的怀孕，并发diseases.Findings 85名妇女符合纳入标准的静脉血栓栓塞，其中两人是用户的孕激素-onyOC。在83例与使用联合OC相关的静脉血栓形成病例中，43例记录为深静脉血栓形成，35例记录为肺血栓形成，5例记录为未另行说明的静脉血栓形成。目前使用任何OC的妇女每10000妇女年的VTE粗率为4.10，使用第二代OC的妇女为3.10，使用第三代制剂的妇女为4.96。校正年龄后，第三代OC使用者与第二代OC使用者的VTE比率为1.68（95% CI 1.04-2.75）。Logistic回归分析显示，第三代和第二代OC使用者之间的VTE风险无显著差异。在第三代孕激素使用者中，去氧孕烯与20 g炔雌醇联合使用者的VTE风险高于孕二烯酮或去氧孕烯与30 g炔雌醇联合使用者。以所有第二代法团为参照，VTE的优势比为3.49去氧孕烯加20 g炔雌醇组为1.21-10.12，（0.66-2.17）的其他第三代孕激素。解释以前报道的增加优势比与第三代OC相比，第二代产品的差异很可能是年龄残留混杂的结果。与含20 μ g炔雌醇和去氧孕烯的产品相比，含30 μ g炔雌醇和去氧孕烯的产品的优势比增加，这在生物学上是不合理的，可能是优先处方的结果，因此是混淆。
Background Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies.Methods We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease.Findings 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-onyy OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens.Interpretation The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 mu g ethinyloestradiol and desogestrel compared with the 30 mu g product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.