BMJ：非口服避孕措施被证实可增加血栓形成风险

前期研究表明，非口服避孕药如皮肤贴片、埋植剂、阴道环可以增加血栓（静脉血栓栓塞）风险，近日刊登在国际著名杂志British Medical Journal上的一篇研究报告又为该结论提供了更多的证据。研究建议，妇女应该将非口服避孕的措施改变为使用避孕药来降低这种血栓风险。已经有很多研究评估了使用口服避孕药片给妇女带来的静脉血栓形成风险，但是很少有研究评估使用非口服避孕措施给妇女带来的血栓风险。这些非口服避孕措施会长期释放激素类进入女性机体以预防怀孕。

这项研究由哥本哈根大学的研究者Øjvind Lidegaard带领，研究者在2001年到2010年间对丹麦15到49岁的经常使用非口服避孕措施的妇女数据进行分析研究，所有妇女在研究开始之前均无血栓症状和癌症。这项研究中，部分因素会影响到研究结果，包括年龄、教育水平，当然这些因素研究者都会考虑进去。

研究结果表明，15-49岁未使用任何激素避孕的福怒发生静脉血栓的风险极低，1000次中平均仅仅会发生2次；然而使用复合口服避孕药的妇女相比前者来说风险增加了三倍（10000次中发生血栓的比例为6.2次）；然而使用皮肤包埋(非口服避孕措施)进行避孕的妇女的血栓形成风险更高，为10000次中发生9.7次；使用阴道环（非口服避孕措施）的妇女生成血栓的风险为，10000次中发生7.8次。

仅仅使用孕激素进行皮下移植的妇女的患病风险略微升高一点点，使用宫内避孕器的妇女患病风险更低，或者宫内避孕器可以给妇女带来某种保护效应，所以使得血栓风险降低。研究者表示，不像复合避孕药那样，长期使用皮肤包埋避孕或者阴道环的妇女，形成血栓的风险并没有下降，基于这些研究结果，研究者对研究对象（2000名使用阴道环的妇女和1250名使用皮肤包埋的妇女）建议，使用包含左炔诺孕酮的复合避孕药片来降低静脉血栓形成的风险。

doi:10.1136/bmj.e2990
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Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10

Øjvind Lidegaard, professor1, Lars Hougaard Nielsen, statistician1, Charlotte Wessel Skovlund, data manager1, Ellen Løkkegaard, senior registrar2

Objective To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.

Design Historical national registry based cohort study.

Setting Four national registries in Denmark.

Participants All Danish non-pregnant women aged 15-49 (n=1 626 158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010.

Main outcome measures Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.

Results Within 9 429 128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10 000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10 000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).

Conclusion Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10 000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.