Sitruk-Ware Regine
Population Council, Center for Biomedical Research, New York, New York.
Fertil Steril. 2016 Nov;106(6):1289-1294. doi: 10.1016/j.fertnstert.2016.08.039. Epub 2016 Sep 24.
The safety of combined hormonal contraceptives (CHCs) has been documented by years of follow-up, and the occurrence of venous thromboembolism (VTE) possibly related to their use is rare in the young population exposed to these agents. The balance between the benefits and risks of contraceptive steroids is generally positive, in particular when compared with pregnancy's risks. Epidemiological studies led to different results showing either no difference in VTE risk between CHCs (active surveillance prospective studies) or an increase in risk (observational or database studies). The discrepancy may be explained by different study designs and the fact that important risk factors such as overweight, family history of thrombosis, and smoking were not adjusted for in some observational studies. To improve the safety of CHC, modifying the estrogen dose and type, selecting newer progestins, and alternative routes of delivery were implemented. Ethinyl- E (EE) exerts a stronger effect than E on estrogen-dependent markers such as liver proteins and coagulation factors. To circumvent the metabolic changes induced by EE, more natural compounds such as E and E valerate (EV) were developed, as well as new progestins structurally closer to P. Progestins when given alone do not increase VTE risk, and their risks and benefits depend upon their chemical structure, the type and dose of combined estrogen, and the delivery route. The lower impact of E-based CHCs on metabolic markers may result in an improved safety profile. A recent study on clinical outcomes supports this hypothesis. In conclusion, CHCs remain a safe and effective choice to prevent unwanted pregnancy, and the risk of VTE is in general low. Careful consideration of individual risk factors should be given before prescribing to avoid cumulative risks and minimize the occurrence of unwanted events.
多年的随访记录了复方激素避孕药(CHC)的安全性,在使用这些药物的年轻人群中,可能与其使用相关的静脉血栓栓塞(VTE)的发生率很低。避孕类固醇的利弊平衡总体上是有利的,特别是与怀孕风险相比。流行病学研究得出了不同的结果,有的显示CHC之间的VTE风险没有差异(主动监测前瞻性研究),有的则显示风险增加(观察性研究或数据库研究)。这种差异可能是由于不同的研究设计,以及一些观察性研究未对超重、血栓形成家族史和吸烟等重要风险因素进行调整。为了提高CHC的安全性,采取了调整雌激素剂量和类型、选择新型孕激素以及采用替代给药途径等措施。炔雌醇(EE)对雌激素依赖性标志物(如肝脏蛋白和凝血因子)的作用比雌二醇(E)更强。为了规避EE引起的代谢变化,研发了更天然的化合物,如E和戊酸雌二醇(EV),以及结构上更接近孕酮(P)的新型孕激素。单独使用孕激素不会增加VTE风险,其风险和益处取决于其化学结构、联合雌激素的类型和剂量以及给药途径。以E为基础的CHC对代谢标志物的影响较小,可能会改善安全性。最近一项关于临床结果的研究支持了这一假设。总之,CHC仍然是预防意外怀孕的安全有效选择,VTE风险总体较低。在开处方前应仔细考虑个体风险因素,以避免累积风险并尽量减少不良事件的发生。