Raps M, Curvers J, Helmerhorst F M, Ballieux B E P B, Rosing J, Thomassen S, Rosendaal F R, van Vliet H A A M
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Chemistry, Catharina Hospital, Eindhoven, the Netherlands.
Thromb Res. 2014 Apr;133(4):640-4. doi: 10.1016/j.thromres.2013.12.041. Epub 2014 Jan 7.
Use of combined hormonal contraceptives is associated with a three- to eight-fold increased risk of venous thrombosis compared with non-use. The thrombotic risk depends on the estrogen dose as well as the progestogen type. Use of hormonal contraceptives leads to resistance to activated protein C (APC), which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is also associated with an increased risk of venous thrombosis, due to increased free Thyroxine (FT4) levels which cause a hypercoagulable state.
The objective of this study was to evaluate the effects of hormonal contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG), and to investigate the effects on APC resistance per contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in 231 users of oral contraceptives.
Users of the most thrombogenic hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or drospirenone, had higher TBG levels than users of less thrombogenic hormonal contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH levels were not significantly elevated and FT4 levels did not change. TBG levels were also associated with APC resistance.
Use of hormonal contraceptives lead to elevated TBG levels, slightly elevated TSH levels and unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased thrombotic risk during the use of hormonal contraceptives cannot be explained by a hyperthyroid state caused by use of these hormonal contraceptives.
与不使用联合激素避孕药相比，使用联合激素避孕药会使静脉血栓形成风险增加三至八倍。血栓形成风险取决于雌激素剂量以及孕激素类型。使用激素避孕药会导致对活化蛋白C（APC）产生抵抗，这可能是静脉血栓形成风险的一个标志物。甲状腺功能亢进也与静脉血栓形成风险增加有关，因为游离甲状腺素（FT4）水平升高会导致高凝状态。
本研究的目的是评估激素避孕药对FT4、促甲状腺激素（TSH）和甲状腺素结合球蛋白（TBG）水平的影响，并研究每个避孕药组对APC抵抗的影响。我们测量了231名口服避孕药使用者的FT4、TBG和TSH水平以及APC抵抗。
使用血栓形成风险最高的激素避孕药（即含有去氧孕烯、醋酸环丙孕酮或屈螺酮的避孕药）的使用者，其TBG水平高于使用血栓形成风险较低的激素避孕药（即含左炔诺孕酮的宫内节育器）的使用者。TSH水平没有显著升高，FT4水平也没有变化。TBG水平也与APC抵抗有关。
使用激素避孕药会导致TBG水平升高、TSH水平略有升高且FT4水平不变，而不会导致甲状腺功能亢进状态。因此，使用激素避孕药期间血栓形成风险增加不能用使用这些激素避孕药导致的甲状腺功能亢进状态来解释。
