THROMBOEMBOLIC DISEASE AND STEROIDAL CONTENT OF ORAL CONTRACEPTIVES - A REPORT TO COMMITTEE ON SAFETY OF DRUGS
THROMBOEMBOLIC DISEASE AND STEROIDAL CONTENT OF ORAL CONTRACEPTIVES - A REPORT TO COMMITTEE ON SAFETY OF DRUGS
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DOI：
10.1136/bmj.2.5703.203
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发表时间：
1970-01-01
影响因子：
105.7
通讯作者：
ENGELUND, A
中科院分区：
文献类型：
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作者：
INMAN, WHW;VESSEY, MP;ENGELUND, A
对英国、瑞典和丹麦药物安全委员会收到的使用口服避孕药后血栓栓塞的报告进行了分析，以研究与各种制剂相关的风险可能存在的差异。为了这个目的，我们将每种产品引起的血栓栓塞的报告数量与市场研究估计的销售分布进行了比较，假设所有产品都具有相同的风险。在英国，发现雌激素剂量与肺栓塞、深静脉血栓形成、脑血栓形成和冠状动脉血栓形成的风险呈正相关。在瑞典和丹麦也发现了静脉血栓形成和肺栓塞的类似关系。在含有相同剂量雌激素的序贯制剂和联合制剂之间，以及两种雌激素（炔雌醇和美雌醇）之间，均未检测到显著差异。数据中的某些差异表明，雌激素的剂量可能不是与血栓栓塞风险相关的唯一因素;因此，与美雌醇100 μg联合用药相关的报告明显不足。去甲炔诺酮2.5mg.与炔雌醇50 μg联合用药相关的报告显著过量。醋酸甲地孕酮4 mg.其他含甲地孕酮的复方制剂也出现了过量的报告，重新检查了早期流行病学研究中获得的数据，尽管其中任何一项研究都没有明显的趋势，综合结果显示，在雌激素剂量最高时，血栓栓塞的病例过多。雌激素剂量与冠状动脉血栓形成风险之间的正相关性的发现特别令人感兴趣，因为以前的研究未能提供口服避孕药与这种情况之间关系的明确证据。
Reports of thromboembolism following the use of oral contraceptives received by drug safety committees in the United Kingdom, Sweden, and Denmark have been analysed to investigate possible differences in the risks associated with the various preparations. For this purpose the numbers of reports of thromboembolism attributed to each product were compared with the distribution that would have been expected from market research estimates of sales, assuming that all products carried the same risk.A positive correlation was found between the dose of oestrogen and the risk of pulmonary embolism, deep vein thrombosis, cerebral thrombosis, and coronary thrombosis in the United Kingdom. A similar association was found for venous thrombosis and pulmonary embolism in Sweden and Denmark. No significant differences could be detected between sequential and combined preparations containing the same doses of oestrogen, nor between the two oestrogens, ethinyloestradiol and mestranol.Certain discrepancies in the data suggest that the dose of oestrogen may not be the only factor related to the risk of thromboembolism; thus there was a significant deficit of reports associated with the combination of mestranol 100 μg. with norethynodrel 2·5 mg. and a significant excess of reports associated with the combination of ethinyloestradiol 50 μg. with megestrol acetate 4 mg. An excess of reports also occurred with other combined preparations containing megestrol acetate.The data obtained in earlier epidemiological studies were re-examined and, though no trend was obvious in any one of them, the combined results showed an excess of cases of thromboembolism at the highest dose of oestrogen.The finding of a positive correlation between the dose of oestrogen and the risk of coronary thrombosis is of special interest since previous studies have failed to provide clear evidence of a relationship between oral contraceptives and this condition.