Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate.

Estrogen replacement therapy (ERT) in postmenopausal women reduces the risk of cardiovascular diseases. Beneficial changes in lipid profiles account for only one part, thereby raising the question of other estrogen induced benefit that may be lost at menopause. The purpose of this study was to determine the effects of estrogen replacement therapy (ERT) on platelet function of postmenopausal women. The effect of 4 weeks ERT (conjugated estrogens 0.625 mg/day) on platelet function was evaluated ex vivo in 18 postmenopausal women (mean age 53 +/- 5 years, after menopause 3.8 +/- 1.9 years). After ERT, (1) plasma concentrations of estrone and estradiol significantly increased (estrone: 16 +/- 7-211+/- 80 pg/ml, estradiol: 14+/- 3-125 +/- 49 pg/ml, P<0.05) and LDL-cholesterol decreased (129 +/- 23-94 +/- 25 mg/dl, P<0.05). Plasma 6-keto-PG F(1) alpha significantly increased (7.2 +/- 3.4-13.3 +/- 6.7 pg/dl, P<0.05). (2) platelet aggregation and positive staining for P-selectin in thrombin- (0.1 and 1.0 U/ml) stimulated platelets were inhibited (Th 0.1 U/ml: 4.0 +/- 0.9-2.4 +/- 1.0/control, P<0.05), but positive staining for GP IIb-IIIa complex did not alter significantly. (3) Ca(2+) influx induced by thrombin decreased (Th 0.3 U/ml: 345 +/- 29-298 +/- 24 nmol/l, P<0.05). The baseline [Ca(2+)](i), the release of Ca(2+) from internal stores induced by thrombin and the size of internal Ca(2+) stores did not alter. (4) platelet c-AMP increased (Th 0.3 U/ml: 66.4 +/- 9.4-82.6 +/- 13.0 fmol/l, P<0.05), but platelet nitrite/nitrate (NO(x)) or c-GMP did not alter significantly. These results suggest that modulation of platelet function by decreasing Ca influx and increased production of c-AMP may account in part for the cardiovascular benefit of ERT.