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 A2 (TxA2), 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 TxA2 (TxB2) 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×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.