Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis

Citation
Ej. Giltay et al., Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis, ART THROM V, 20(5), 2000, pp. 1396-1403
Citations number
50
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
10795642 → ACNP
Volume
20
Issue
5
Year of publication
2000
Pages
1396 - 1403
Database
ISI
SICI code
1079-5642(200005)20:5<1396:OBNTAO>2.0.ZU;2-E
Abstract
Oral estrogen administration decreases plasma levels of tissue-type plasmin ogen activator (tPA), which may be explained by a decrease in endothelial t PA synthesis, an increase in its hepatic clearance, or both. In the present study, we determined (1) differences between oral (ie, via the liver) ethi nyl estradiol and transdermal (ie, systemic) 17 beta-estradiol administrati on on plasma antigen levels of tPA and plasminogen activator inhibitor type -1 before and after 4 months of hormone administration and (2) effects on e ndothelial tPA synthesis, by measuring the local increase in plasma tPA dur ing venous occlusion of the upper extremity. Thirty transsexual males (medi an age 32 years, range 20 to 44 years) were randomly assigned to either ora l ethinyl estradiol (n=15) or transdermal 17 beta-estradiol (n=15); both tr eatments included the antiandrogen cyproterone acetate (CA). Ten males were treated with CA alone. Seventeen transsexual females (median age 27 years, range 18 to 37 years) were treated with intramuscular testosterone esters. Only oral ethinyl estradiol plus CA but neither transdermal 17 beta-estrad iol plus CA, nor oral CA, nor parenteral testosterone lowered plasma tPA an d plasminogen activator inhibitor-1 (P<0.001 for both). tPA release during venous occlusion was not affected by oral ethinyl estradiol plus CA in male s (P=0.52) or by parenteral testosterone in females (P=0.89). These data ar e consistent with a previous observation, in rodents, that the decrease in tPA after oral estrogen administration can be explained by an increase in h epatic tPA clearance, leaving endothelial tPA synthesis unchanged, and sugg est that these mechanisms also explain the decrease in tPA in humans.