Hormone Therapy and Fibrinolysis
Hormone Therapy and Fibrinolysis
Plasminogen-activator inhibitor type 1 is an antagonist of fibrinolysis in humans and is present in endothelial cells and smooth muscle cells of healthy arteries. At menopause, levels of PAI-1 increase, and studies have shown that increases are associated with atherosclerosis and its ischemic consequences. To date, although estrogen alone has been demonstrated to reduce PAI-1, no study has addressed the comparative impact of estrogen plus progestin vs. estrogen alone.
In 50 postmenopausal women, the effects of estrogen alone (as oral conjugated estrogen 0.625 mg/d or transdermal estradiol 0.1 mg/d) were compared with estrogen plus medroxyprogesterone acetate (MPA) 2.5 mg daily.
After one month, all regimens had an equally favorable effect on LDL and HDL cholesterol, consistent with the earlier PEPI trial. On the other hand, only the oral estrogen regimens were effective in reducing PAI-1 (by approximately 50%), whereas there was no effect induced by the transdermal estradiol administration, with or without progesterone. Transdermal estradiol has been previously shown to have a more favorable antioxidant effect in protecting LDL from oxidation than oral conjugated estrogen.
The authors attribute some of the beneficial effect of oral estrogen to the hepatic effects on clearance and/or synthesis of PAI-1, an effect not obtained using transdermal estrogens.
Koh KK, et al. N Engl J Med 1997; 336:683-690.
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