Farmer R D, Lawrenson R A
Department of Public Health and Epidemiology, Imperial College of Science, Technology, and Medicine, University of London, Guilford, England.
Am J Obstet Gynecol. 1998 Sep;179(3 Pt 2):S78-86. doi: 10.1053/ob.1998.v179.a92634.
Three research articles published in late 1995 and early 1996 suggested that oral contraceptives containing either of the newer progestogens (gestodene or desogestrel) could be associated with an increased risk of venous thromboembolism. During the months after the initial publications, the results have been scrutinized with great care and further studies have been published. The findings of 2 recent database studies, 1 in the United Kingdom and 1 in Germany, are presented in this article.
The average age of users of combined oral contraceptives in Germany was 27 years, compared with 26 years in the United Kingdom. In Germany the use of gestodene-based products was lower than that in the United Kingdom. In the United Kingdom the users of desogestrel with 20 microg ethinyl estradiol (Mercilon) were older than the users of desogestrel with 30 microg ethinyl estradiol (Marvelon).
The crude incidence of venous thromboembolism in the UK study was 4.1 cases/10,000 woman-y exposure to combined oral contraceptives. In Germany it was 4.2 cases/10,000 woman-y. In Germany the rates among users of second-generation combined oral contraceptives were higher than those among users of third-generation products. The reverse was the case in the United Kingdom. In the United Kingdom the crude incidence rates were higher for the 20 microg estrogen desogestrel product than for the 30 microg product. CASE-CONTROL ANALYSIS: The adjusted odds ratios in the UK study did not show significant increases for desogestrel or gestodene compared with levonorgestrel products. There were inconsistencies in the results among centers in the 2 international studies (the World Health Organization and Transnational studies). In both there was a consistent inverse dose-response relationship with estrogen in all centers.
The limitations of the observational studies are such that the hypothesis that the newer progestogens are more likely to cause venous thromboembolism cannot be proved.
1995年末和1996年初发表的三篇研究文章表明，含有新型孕激素（孕二烯酮或去氧孕烯）之一的口服避孕药可能与静脉血栓栓塞风险增加有关。在最初发表文章后的几个月里，研究结果得到了仔细审查，并且有更多研究发表。本文介绍了最近两项数据库研究的结果，一项来自英国，一项来自德国。
德国复方口服避孕药使用者的平均年龄为27岁，而英国为26岁。在德国，基于孕二烯酮的产品使用比例低于英国。在英国，服用含20微克炔雌醇去氧孕烯片（美欣乐）的使用者比服用含30微克炔雌醇去氧孕烯片（妈富隆）的使用者年龄更大。
英国研究中静脉血栓栓塞的粗发病率为每10000名女性使用复方口服避孕药年4.1例。在德国为每10000名女性使用复方口服避孕药年4.2例。在德国，第二代复方口服避孕药使用者的发病率高于第三代产品使用者。英国的情况则相反。在英国，含20微克雌激素的去氧孕烯产品的粗发病率高于含30微克雌激素的产品。病例对照分析：英国研究中，与左炔诺孕酮产品相比，去氧孕烯或孕二烯酮的校正比值比未显示出显著增加。两项国际研究（世界卫生组织和跨国研究）中各中心的结果存在不一致。在这两项研究中，所有中心雌激素与发病率均呈现一致的剂量反应负相关。
观察性研究存在局限性，因此无法证实新型孕激素更易导致静脉血栓栓塞这一假设。
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