Farmer R D, Lawrenson R A, Todd J C, Williams T J, MacRae K
European Institute of Health and Medical Sciences, University of Surrey, Guildford, UK.
Hum Reprod Update. 1999 Nov-Dec;5(6):688-706. doi: 10.1093/humupd/5.6.688.
The results of three independent studies of venous thromboembolic disease (VTE) and oral contraceptives are reviewed together with two further cohort/case-control studies which we conducted using the MediPlus and General Practice Research Database (GPRD) databases. These latter studies jointly involved 395 cases and uniquely examined the association between VTE and individual combined oral contraceptive (COC) formulations. The two studies yielded very similar results. Crude incidence rates for idiopathic VTE of 4.6 and 3.8 were found per 10,000 exposed woman-years (EWY), in the MediPlus and GPRD studies respectively. Incidence rates increased markedly with age, and in both databases the rates amongst users of levonorgestrel products were lower than those amongst users of desogestrel and gestodene products. A case fatality rate of 3% and a mortality rate of 10 per million EWY were estimated. Odds ratios (OR) were calculated for confounding variables and different COC formulations. Both database studies indicated an excess of current smokers and women with high body mass indices amongst cases. There were significantly more cases with asthma in the GPRD study and cases who had been using their COC for less than a year. No statistically significant differences between COC formulations were found in the analyses where controls were matched to cases by practice and year of birth in both the MediPlus and GPRD studies. In the GPRD study we also ran a study where controls were matched by practice and within 5 year age bands. In this study the OR were consistently higher for the newer or 'third generation' products than when controls were matched by year of birth. However only the acne formulation/OC containing cyproterone acetate and 35 microg ethinyloestradiol yielded a significant OR of 2.3. It may be concluded that improvements in prescribing are paramount as the results strongly indicate that overweight women and those who smoke are at a greater risk of VTE. Further study is required to elucidate the possibility that asthma or its treatment may predispose to VTE, alone or in combination with other risk factors. However, neither the MediPlus nor GPRD studies indicate that any one COC formulation poses a greater risk of VTE than another.
对三项关于静脉血栓栓塞性疾病（VTE）与口服避孕药的独立研究结果，以及我们利用MediPlus数据库和全科医学研究数据库（GPRD）开展的另外两项队列/病例对照研究结果进行了综述。后两项研究共涉及395例病例，并专门研究了VTE与各种复方口服避孕药（COC）制剂之间的关联。这两项研究得出了非常相似的结果。在MediPlus研究和GPRD研究中，每10000名暴露妇女年（EWY）的特发性VTE粗发病率分别为4.6和3.8。发病率随年龄显著增加，且在两个数据库中，左炔诺孕酮产品使用者的发病率均低于去氧孕烯和孕二烯酮产品使用者。估计病例死亡率为3%，每百万EWY的死亡率为10。计算了混杂变量和不同COC制剂的优势比（OR）。两项数据库研究均表明，病例中当前吸烟者和体重指数高的女性比例过高。在GPRD研究中，哮喘患者以及使用COC不到一年的患者明显更多。在MediPlus和GPRD研究中，当按诊所和出生年份将对照与病例匹配时，分析未发现COC制剂之间存在统计学显著差异。在GPRD研究中，我们还进行了一项按诊所和5岁年龄组匹配对照的研究。在这项研究中，与按出生年份匹配对照相比，新型或“第三代”产品的OR始终更高。然而，只有含醋酸环丙孕酮和35微克炔雌醇的抗痤疮制剂/口服避孕药产生了显著的OR值2.3。可以得出结论，由于结果强烈表明超重女性和吸烟者发生VTE的风险更高，因此改善处方开具至关重要。需要进一步研究以阐明哮喘或其治疗单独或与其他风险因素结合可能导致VTE的可能性。然而，MediPlus研究和GPRD研究均未表明任何一种COC制剂比另一种制剂造成VTE的风险更大。
