Conard J
Unité Hémostase-Thrombose, Service d'Hématologie Biologique, Paris, France.
Hum Reprod Update. 1999 Nov-Dec;5(6):672-80. doi: 10.1093/humupd/5.6.672.
An increased risk of venous thrombosis has been demonstrated in women receiving oral contraceptives (OCs). This risk has been primarily associated with the oestrogen content, but recent studies showed that the progestogen may also play a role. A higher risk was found with the so-called third-generation (desogestrel, gestodene) as compared with the second-generation progestogens (levonorgestrel). The risk was approximately two-fold. These unexpected results have been the subject of many debates, and bias--such as selection bias--has been suggested. The existence of bias cannot be completely excluded, but the thrombotic risk seems however to be slightly higher with the third-generation progestins. Haemostatic changes have been observed during OC intake. Both coagulation and fibrinolytic activity are increased: the beneficial profibrinolytic effect may counterbalance the deleterious procoagulant effect. This may explain that the absolute risk of venous thromboembolism is low during OC treatments. Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. The biological plausibility of the increased risk related to the third-generation progestogens has been explored. Theoretically, this could be due to an increased coagulation or to a lack of increased fibrinolysis as compared with second-generation progestogens. The only difference presently reported with third-generation OCs is a decreased sensitivity to activated protein C, possibly resulting in a hypercoagulability of greater magnitude. The selection bias suggested in epidemiological studies may also exist for the latter study, as women taking third- or second-generation OCs were not randomized. The possible increased risk related to third-generation OCs should not change the known general contra-indications. Practical guidelines are proposed for women with personal or family history of venous thromboembolism, and for those with a congenital cause of thrombophilia.
已证实服用口服避孕药（OCs）的女性静脉血栓形成风险增加。这种风险主要与雌激素含量有关，但最近的研究表明孕激素也可能起作用。与第二代孕激素（左炔诺孕酮）相比，所谓的第三代（去氧孕烯、孕二烯酮）孕激素的风险更高。风险约为两倍。这些意外结果引发了许多争论，并有人提出存在偏差，如选择偏差。虽然不能完全排除偏差的存在，但第三代孕激素的血栓形成风险似乎略高。在服用OCs期间观察到了止血变化。凝血和纤溶活性均增加：有益的纤溶作用可能会抵消有害的促凝作用。这可以解释为什么OC治疗期间静脉血栓栓塞的绝对风险较低。一些有预先存在的止血异常的女性，如抗凝血酶缺乏或存在因子V莱顿突变导致的活化蛋白C抵抗，可能风险更高。已经探讨了与第三代孕激素相关的风险增加的生物学合理性。从理论上讲，这可能是由于与第二代孕激素相比，凝血增加或纤溶没有相应增加。目前报道的第三代OCs的唯一差异是对活化蛋白C的敏感性降低，这可能导致更大程度的高凝状态。在流行病学研究中提出的选择偏差在后者的研究中也可能存在，因为服用第三代或第二代OCs的女性并非随机分组。与第三代OCs相关的可能增加的风险不应改变已知的一般禁忌症。针对有个人或家族静脉血栓栓塞病史的女性以及有先天性血栓形成倾向原因的女性，提出了实用指南。
