Postmenopausal hormone replacement therapy increases plasmatic thromboxane β2

Objective: This study shows the effect of hormone replacement therapy (HRT), using oral estrogen exclusively or in combination with progestin, on platelet activation in healthy menopaused women. Background: Recent evidence from studies of postmenopausal HRT in healthy women demonstrated a short-time increased risk of coronary heart disease. Platelet activation, which generates vasoconstrictory thromboxane A(2) (TxA(2)), has been related to the risk of cardiovascular diseases. Methods: By means of a placebo-controlled study twenty-seven postmenopausal patients were continuously orally administered estrogen in combination with progestin or estrogen exclusively for an 8-week period. Platelet activation was evaluated by flow cytometric P-selectin expression and by enzyme immunoassay plasmatic TxA(2) (TxB(2)) concentrations. Results: P-selectin binding index changed from 6.3 +/- 3.6 to 7.0 +/- 3 in the placebo group (n=10); from 5.9+2.2 to 7.9 +/- 3.3 in the E+P group (n=8) and from 6.4+2.7 to 7.1 +/- 1.9 in the E group (n=9). Plasma concentrations of TxB2 before and after intervention, changed from 1.2+1.2 to 1.5+1.4 (pg/well) in the placebo group; significantly (p=0.005) in the E+P group (n=8), from 0.9+0.3 to 6.1+6.5 (pg/well), and from 1.3+1.5 to 0.8+0.4 (pg/well) in the E group (n=8; mean+standard deviation, basal x therapy, p < 0.05). Conclusions: Healthy menopaused women who were administered estradiol in association with norethisterone continuously had an increase of plasmatic thromboxane, possibly determined by platelet activation, which indicates a higher short-term thrombotic risk. P-selectin expression analyses failed to demonstrate the impact of HRT on platelets. (c) 2005 Elsevier Ireland Ltd. All rights reserved.