Skouby Sven O, Sidelmann Johannes J
Reproductive Medicine Unit, Department of Obstetrics and Gynecology, Herlev/Gentofte Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Phone: +45 38683796, Secretary: +45 38688272.
Unit for Thrombosis Research, Institute of Regional Health Research, Faculty of Health Science, University of Southern Denmark and Department of Clinical Biochemistry, Hospital of Southwest Denmark, Esbjerg, Denmark.
Horm Mol Biol Clin Investig. 2018 Nov 17;37(2):hmbci-2018-0041. doi: 10.1515/hmbci-2018-0041.
Combined hormonal contraception containing estrogen and progestogen and postmenopausal hormone therapy with estrogen ± progestogen are reported risk factors for venous thrombosis. The thrombotic risk varies by estrogen dose and type of progestogen. Estrogen combined with "newer generation" progestogens in combined oral contraceptives may have higher thrombotic risk than estrogen combined with older generation progestogens. Among postmenopausal women thrombotic risk also varies by type of hormone and mode of delivery. Although the risk of thrombosis with the different hormonal compounds is uncertain, it has definitely been attributed to the pharmacological effect of the hormones on hemostasis. Animal and cell culture studies have demonstrated the pharmacodynamics of progestogens with respect to hemostasis. Extrapolation from these studies to clinical conditions and further to clinical end points such as cardiovascular disease is, however, controversial. Few clinical studies have focused on the effect of progestogen only therapy on the hemostatic system in vivo. Most of the current knowledge regarding the in vivo effect of progestogens on hemostasis is obtained from studies with combined contraceptives. These results obviously reflect the combined influence of both estrogen and progestogen on hemostasis, and extrapolation to progestogen-only conditions is challenging. This paper discusses the pharmacodynamics of progestogens in relation to the hemostatic system, addressing results obtained in animal and cell culture studies and in clinical studies employing progestogen-only and combined oral contraceptives. The compiled results suggest that the major effect of progestogens on hemostasis is related to alterations in platelet function and the tissue factor pathway of coagulation. More studies focusing on these topics are warranted.
据报道，含有雌激素和孕激素的复方激素避孕药以及雌激素±孕激素的绝经后激素疗法是静脉血栓形成的危险因素。血栓形成风险因雌激素剂量和孕激素类型而异。复方口服避孕药中雌激素与“新一代”孕激素联合使用时的血栓形成风险可能高于雌激素与老一代孕激素联合使用时的风险。在绝经后女性中，血栓形成风险也因激素类型和给药方式而异。尽管不同激素化合物导致血栓形成的风险尚不确定，但肯定归因于激素对止血的药理作用。动物和细胞培养研究已经证明了孕激素在止血方面的药效学。然而，将这些研究结果外推至临床情况以及进一步外推至心血管疾病等临床终点存在争议。很少有临床研究关注单纯孕激素疗法对体内止血系统的影响。目前关于孕激素对体内止血作用的大多数知识来自复方避孕药的研究。这些结果显然反映了雌激素和孕激素对止血的综合影响，外推至仅使用孕激素的情况具有挑战性。本文讨论了孕激素与止血系统相关的药效学，阐述了动物和细胞培养研究以及使用单纯孕激素和复方口服避孕药的临床研究所得出的结果。汇总结果表明，孕激素对止血的主要作用与血小板功能和凝血组织因子途径的改变有关。有必要开展更多关注这些主题的研究。
