The effect of oral contraceptives on antiaggregatory prostacyclin and proaggregatory thromboxane A2 in humans.

The effect of different types of oral contraceptives on the productions of antiaggregatory prostacyclin (PGI2) and proaggregatory thromboxane A2 (TxA2) was studied by measuring the stable metabolites of these prostanoids, that is, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), respectively, from plasma. In addition, the capacity of the platelets to produce TxB2 during spontaneous clotting was studied by measuring the TxB2 levels from the serum incubated at +37 degrees C for 60 minutes. The material consisted of 48 women who had used estrogen-containing oral contraceptives for 2.0 +/- 1.9 years (mean +/- SD), 24 women using progestogen-only pills for 3.7 +/- 2.0 years, and 42 women of the same age using no oral contraceptives or intrauterine contraceptive device. The plasma concentrations of 6-keto-PGF1 alpha in women with combined oral contraceptives (65.5 +/- 16.1 pg/ml, mean +/- SD) was lower (p less than 0.01) than that in the control subjects (77.4 +/- 26.4 pg/ml), whereas the use of combined oral contraceptives was associated with no changes in TxB2 levels in plasma or serum, in women with progestogen-only oral contraceptives, the plasma levels of 6-keto-PGF1 alpha and TxB2 were normal, but the capacity of the platelets to release TxB2 during spontaneous clotting was decreased (113.6 +/- 77.6 ng/ml versus 179.9 +/- 81.9 ng/ml, p less than 0.05). In a prospective trial on 11 women, who started using 30 microgram of ethinyl estradiol and 150 microgram of levonorgestrel, no changes in PGI2 or TxA2 were seen during the first 3 months of usage. The decrease in antiaggregatory PGI2 during the prolonged use of estrogen-containing oral contraceptives may be associated with the increased risk of thromboembolism.