Castellsague J, Pérez Gutthann S, García Rodríguez L A
Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
Drug Saf. 1998 Feb;18(2):117-23. doi: 10.2165/00002018-199818020-00003.
The association between use of hormone replacement therapy (HRT) and the risk of venous thromboembolism (VTE) has been assessed in relatively few epidemiological studies. Evidence from the earliest studies did not support an increased risk of VTE among HRT users. However, methodological limitations in most studies, including small sample size and inadequate control of confounding, did not allow firm conclusions to be made. Most of these limitations have been overcome in 5 recent studies which consistently show that the risk of VTE among women currently using HRT is 2 to 3 times higher than among women not using HRT. The overall relative risk of VTE for women currently using HRT obtained from these studies was 2.6 (95% confidence interval 1.6 to 4.2). This association is unlikely to be explained by confounding or other potential biases affecting observational studies. The risk appears to be more prominent during the first year of HRT use, and in 2 studies the risk disappeared after the first year of therapy. A dose-response relationship, with a doubling of risk among users of high doses of estrogens, was shown in 2 of these studies. No major differences were observed with the different types of therapy, but users of unopposed estrogen therapy and transdermal therapy might be at lower risk than users of opposed regimens and oral preparations. Evidence from these new studies indicates that, among healthy post-menopausal women, between 1 and 2 additional cases of VTE per 10,000 women can be annually attributed to current use of HRT. The Committee on Safety of Medicines in the UK evaluated this risk as small and considered that it does not change the overall benefit-risk profile of HRT for most women.
相对较少的流行病学研究评估了激素替代疗法（HRT）的使用与静脉血栓栓塞（VTE）风险之间的关联。最早的研究证据并不支持HRT使用者发生VTE的风险增加。然而，大多数研究存在方法学上的局限性，包括样本量小和混杂因素控制不足，这使得无法得出确凿的结论。最近的5项研究克服了这些局限性中的大多数，这些研究一致表明，目前使用HRT的女性发生VTE的风险比未使用HRT的女性高2至3倍。从这些研究中得出的目前使用HRT的女性发生VTE的总体相对风险为2.6（95%置信区间为1.6至4.2）。这种关联不太可能由影响观察性研究的混杂因素或其他潜在偏倚来解释。风险似乎在使用HRT的第一年更为突出，在两项研究中，治疗一年后风险消失。其中两项研究显示了剂量反应关系，高剂量雌激素使用者的风险增加了一倍。不同类型的治疗方法未观察到重大差异，但单纯雌激素治疗和经皮治疗的使用者可能比联合用药方案和口服制剂的使用者风险更低。这些新研究的证据表明，在健康的绝经后女性中，每10000名女性中每年有1至2例额外的VTE病例可归因于目前使用HRT。英国药品安全委员会评估这种风险较小，并认为这不会改变HRT对大多数女性的总体效益风险状况。
