Platelet activation status decreases after menopause.

OBJECTIVE: The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation. BACKGROUND: Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women. METHODS: By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb-IIIa complex (GPIIb-IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets x mean fluorescence of positive platelets). Also, thromboxane A2 was quantified by means of its main plasma metabolite, thromboxane B2, by enzyme immunoassay. RESULTS: P-selectin and GPIIb-IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin+ platelets and of GPIIb-IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3 +/- 3, n = 10) and Group B (6.2 +/- 2.9, n = 27; mean +/- standard deviation (SD), p < 0.001). GPIIb-IIIa binding index also differed significantly between both groups (Group A: 18.8 +/- 2.3, n = 10 vs. Group B: 16.2 +/- 3.1, n = 27; mean +/- SD, p < 0.0018). Plasma concentration of thromboxane B2 was 1.07 +/- 0.5 pg/well before menopause (Group A, n = 10) and 1.9 +/- 4.1 pg/well after menopause (Group B, n = 27), not significantly different (mean +/- SD, baseline x therapy, p = 0.85). CONCLUSIONS: After the menopause, climacteric women--whose estradiol status is low--have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.

Postmenopausal hormone replacement therapy increases plasmatic thromboxane beta 2.

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 TxB(2) 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.