Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women
Abstract
Oral hormone therapy (HT) is associated with an increased risk of venous thromboembolism (VTE), with the highest risk during the first year of treatment. Differences in the formulation, dose and duration of HT may affect the risk of VTE. A clinical trial was conducted to compare the effects of different oral HT regimens on thrombin generation and efficiency of fibrinolysis in postmenopausal women. 150 postmenopausal women were assigned in a randomized controlled study in which the effect of standard dose (1 mg of 17ß-estradiol / 5 mg of dydrogesterone), ultra-low-dose HT (0.5 mg of 17ß-estradi-ol / 2.5 mg of dydrogesterone) on fibrinolysis and coagulation was compared to controls. Factors measured included plasma clot lysis time (CLT), fibrinolysis activators and inhibitors, thrombin generation (prothrombin fragments 1+2 [F 1+2], endogenous thrombin potential [ETP]), normalized activated protein C sensitivity ratio (nAPCsr), and factor (F)Viii activity and were determined before and after 24 weeks of HT. The results demonstrated that in contrast to the standard HT, ultra-low-dose HT may enhance fibrinolysis through reduced PAi-1 levels. The current study is the first to show significant differences between combined oral ultra-low-dose HT and standard HT in the effects on fibrinolysis and thrombin generation in postmenopausal women.
About the Authors
I. V. Kuznetsova
First Moscow State Medical University n.a. I.M. Sechenov
Russian Federation
Russian Federation
Yu. S. Drapkina
National Medical Research Centre for Obstetrics, Gynecology and Perinatology n.a. academician V.I. Kulakov
Russian Federation
Russian Federation
References
1. Ведение женщин в пери- и постменопаузе: практические рекомендации / Под ред. В. П. Сметник, Л. М. Ильиной. - М.: Ярославль: ООО «ИПК «Литера», 2010. - 221 с.
2. Stuenkel C.A., Davis SR, Gompel A., Lumsden M.A., Murad M.H., Pinkerton J.V. et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100: 3975-4011.
3. Canonico M. Hormone therapy and risk of venous thromboembolism among postmenopausal women. Maturitas 2015; 82: 304-7.
4. Undas A. Fibrin clot properties and their modulation in thrombotic disorders. Thromb Haemost 2014; 112: 32-42.
5. Undas A., Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31:88-99.
6. Undas A., Zawilska K., Ciesla-Dul M., et al. Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives. Blood 2009; 114: 4272-8.
7. Zolcinski M., Ciesla-Dul M., Undas A. Effects of atorvastatin on plasma fibrin clot properties in apparently healthy individuals and patients with previous venous thromboembolism. Thromb Haemost 2012; 107: 1180-2.
8. Salobir B.G., Keber I., Vrabic L. A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women. Fertil Steril 2002; 78: 1178-83.
9. Scarabin P.Y., Hemker H.C., Clément C., Soisson V., Alhenc-Gelas M., et al. Increased thrombin generation among postmenopausal women using hormone therapy: importance of the route of estrogen administration and progestagens. Menopause 2011; 18: 873-9.
10. Teede H.J., McGrath B.P., Smolich J.J., Malan E., Kotsopoulos D., Liang Y.L., et al. Postmenopausal hormone replacement therapy increases coagulation activity and fibrinolysis. Arterioscler Thromb Vasc Biol 2000; 20: 1404-9.
11. Koh K.K., Shin M.S., Sakuma I., Ahn J.Y., Jin D.K., Kim H.S. et al. Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women. Arterioscler Thromb Vasc Biol 2004; 24: 1516-21.
12. Norris L.A., Brosnan J., Bonnar J., et al. Inhibitors and activation markers of the haemostatic system during hormone therapy: a comparative study of oral estradiol (2 mg) / dydrogesterone and estradiol (2 mg) / trimegestone. Thromb Haemost 2008; 100: 253-60.
13. Brosnan J.F., Sheppard B.L., Norris L.A. Haemostatic activation in post-menopausal women taking low-dose hormone therapy: less effect with transdermal administration? Thromb Haemost 2007; 97: 558-65.
14. Kalela A., Jokela H., Lehtimäki T., et al. Effect of the cessation of long-term.
15. Meltzer M.E., Lisman T., de Groot P.G. et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116: 113-21.
16. Meltzer M.E., Doggen C.J., de Groot P.G., Rosendaal F.R., Lisman T., et al. The impact of the fibrinolytic system on the risk of venous and arterial thrombosis. Semin Thromb Hemost 2009; 35: 468-77.
17. Pankiw-Bembenek O., Zalewski J., Goralczyk T., Undas A. A history of early stent thrombosis is associated with prolonged clot lysis time. Thromb Haemost 2012; 107: 513-20.
18. Sztefko K., Rogatko I., Milewicz T., Jôzek K., Tomasik P.J., Szafran Z. et al. Effect of hormone therapy on the enteroinsular axis. Menopause 2005; 12: 630-8.
19. Kurdee Z., King R., Ajjan R.A. The fibrin network in diabetes: its role in thrombosis risk. Pol Arch Med Wewn 2014; 124: 617-27.
Review
For citations:
Kuznetsova I.V., Drapkina Yu.S. Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women. Medical alphabet. 2018;2(13):35-38. (In Russ.)
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