Background. - Although estrogen has been shown to contribute to retardation of the development of coronary heart disease in premenopausal women, the efficacy of hormone replacement therapy for coronary heart disease prevention in women with established coronary heart disease remains controversial. Hence, additional research is needed to clarify the effects of hormone replacement therapy on the cardiovascular and clotting systems. We investigated the effect of estrogen on platelet aggregation induced by standard agonists (epinephrine and adenosine diphosphate), with and without the platelet antagonist aspirin. Furthermore, we analyzed our data according to the presence or absence of a prevalent polymorphism of the glycoprotein (GP) IIIa subunit of the platelet fibrinogen receptor GPIIb-IIIa, PIA2. Methods and Results. - The effect of estrogen on aggregation of platelets was studied in healthy men (n = 20, 10 PIA1/A1 and 10 PIA1/A2) and premenopausal healthy women (n = 10, 5 PIA1/A1 and 5 PIA1/A2). The PIA1/A1 and PIA1/A2 individuals were matched for age and race. Platelet response to agonists was investigated in the presence of (1) estrogen (10-11 to 10-8 mol/L), (2) aspirin (0.056 to 56 μmol/L), (3) estrogen plus aspirin, and (4) estrogen plus ICI 182 780 (ICI, 10-9 mol/L, an inhibitor of the estrogen receptor). We found that physiologic concentrations of estrogen strongly and significantly inhibited the aggregation of PIA1/A2 platelets (P < .005 for epinephrine and P < .05 for adenosine diphosphate, induced aggregation, respectively) in both men and women. Concentrations of estrogen that were 1000-fold greater were required to observe the same level of inhibition with PIA1/A1 platelets. In the presence of aspirin, estrogen failed to provide additional inhibitory effect on aggregation of both PIA1/A1 and PIA1/A2 platelets. The estrogen-specific inhibitor ICI blocked the effect of estrogen on aggregation, suggesting that this effect is mediated by the estrogen receptor. Conclusions. - Estrogen inhibits the aggregation of platelets, but such inhibition is highly dependent on the presence or absence of the PIA2 polymorphism of GPIIIa. However, in the presence of aspirin, the inhibitory effect of estrogen on aggregation was no longer detectable.
|Original language||English (US)|
|Number of pages||4|
|Journal||Archives of Pathology and Laboratory Medicine|
|State||Published - 2001|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Medical Laboratory Technology