Lewis M A, Heinemann L A, MacRae K D, Bruppacher R, Spitzer W O
Potsdam Institute of Pharmacoepidemiology and Technology Assessment (PIPTA), Germany.
Contraception. 1996 Jul;54(1):5-13. doi: 10.1016/0010-7824(96)00112-6.
A matched case-control study was undertaken in 10 centers in Germany and the United Kingdom to explore the association of current use of major combination oral contraceptives with the occurrence of venous thromboembolism. The cases recruited were 505 women aged 16-44 years with venous thromboembolism, controls were 1877 women (at least 3 controls per case) matched for 5-year age group and region without VTE. The main outcome measures were odds ratios derived by comparing current use of a specific oral contraceptive or group of OC against current use of other groups or against no current use of OC. The odds ratios (95% confidence intervals) for venous thromboembolism were: for third generation products (low dose ethinyloestradiol, gestodene and desogestrel) versus second generation products (low dose ethinyloestradiol, no gestodene and desogestrel, 1.5 (1.1 to 2.0), for third versus second generation products with norgestimate included in third generation, 1.6 (1.2 to 2.2). The odds ratios for current use for women aged 16-44 of specific progestagens versus levonorgestrel-containing compounds were 1.7 (1.1 to 2.6) for gestodene, 1.8 (1.2 to 2.6) for desogestrel, 1.9 (1.0 to 3.6) for norgestimate and 1.3 (0.7 to 2.5) for progestagen-only pills. For women aged 25 to 44 likely to be exposed to any of these progestagens, odds ratios for the comparison of progestagens versus levonorgestrel showed a successive increase by market introduction ranging from 1.5 (0.9 to 2.5) for desogestrel with 30 micrograms oestrogen content (introduced 1981) to 2.8 (1.3 to 6.5) for desogestrel with 20 micrograms oestrogen content (introduced 1992) significant in linear trend analysis (p = 0.00012). The influence of norgestimate classification as third or second generation product does not significantly alter the results regarding the association of third generation products and venous thromboembolism. A direct comparison of current use of norgestimate (which is primarily metabolized to levonorgestrel) versus levonorgestrel shows an increased odds ratio. The trend of increasing risk of progestagens by recency of market introduction when compared with levonorgestrel is strongly indicative of the existence of external bias due to attrition of susceptibles.
在德国和英国的10个中心开展了一项匹配病例对照研究，以探讨目前使用主要复方口服避孕药与静脉血栓栓塞发生之间的关联。招募的病例为505名年龄在16 - 44岁的静脉血栓栓塞女性，对照为1877名女性（每个病例至少有3名对照），按5岁年龄组和地区匹配且无静脉血栓栓塞。主要结局指标是通过比较特定口服避孕药或口服避孕药组的当前使用情况与其他组的当前使用情况或不使用口服避孕药的情况得出的比值比。静脉血栓栓塞的比值比（95%置信区间）为：第三代产品（低剂量炔雌醇、孕二烯酮和去氧孕烯）与第二代产品（低剂量炔雌醇但不含孕二烯酮和去氧孕烯）相比为1.5（1.1至2.0），第三代产品包含诺孕酯时与第二代产品相比为1.6（1.2至2.2）。16 - 44岁女性使用特定孕激素与含左炔诺孕酮化合物的当前使用情况的比值比为：孕二烯酮为1.7（1.1至2.6），去氧孕烯为1.8（1.2至2.6），诺孕酯为1.9（1.0至3.6），仅含孕激素的药丸为1.3（0.7至2.5）。对于年龄在25至44岁可能接触这些孕激素中的任何一种的女性，孕激素与左炔诺孕酮比较时的比值比显示，随着上市时间的推移呈连续增加，从含30微克雌激素的去氧孕烯（1981年上市）的1.5（0.9至2.5）到含20微克雌激素的去氧孕烯（1992年上市）的2.8（1.3至6.5），线性趋势分析具有显著性（p = 0.00012）。将诺孕酯分类为第三代或第二代产品对第三代产品与静脉血栓栓塞关联的结果没有显著影响。直接比较诺孕酯（主要代谢为左炔诺孕酮）与左炔诺孕酮的当前使用情况显示比值比增加。与左炔诺孕酮相比，孕激素因上市时间近而风险增加的趋势强烈表明存在因易感人群流失导致的外部偏倚。
