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OBJECTIVE: We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane [A.sub.2], in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin [F.sub.1[alpha]] and 2,3-dinor-6-keto-prostaglandin [F.sub.1[alpha]]) and those of thromboxane [A.sub.2] (thromboxane [B.sub.2], 2,3-dinor-thromboxane [B.sub.2]). STUDY DESIGN: Thirty-three women in preterm labor between 25 and 34 weeks of gestation were studied before, during, and after treatment with indomethacin (n = 16) or nylidrin (n = 17). Urinary prostanoid levels were determined by high-performance liquid chromatography followed by radioimmunoassay, and the excretion was expressed as nanograms of prostanoids per millimole of creatinine. Statistical analyses were done by paired and unpaired Student test, by Spearman's correlation, and by Wilcoxon signed-rank test. RESULTS: Preterm labor was accompanied by a median 32% higher output of prostacyclin and thromboxane [A.sub.2] metabolites as compared with those in 25 controls. At 8 hours after the start of treatment indomethacin induced maximal drops in 6-keto-prostaglandin [F.sub.1[alpha]] (70%), in dinor-6-keto-prostaglandin [F.sub.1[alpha]] (60%), in thromboxane [B.sub.2] (85%), and in dinor-thromboxane [B.sub.2] (95%) excretion. Within 1 week after the cessation of indomethacin, output of prostacyclin metabolites had recovered to pretreatment values, whereas output of thromboxane [A.sub.2] metabolites was yet lower than the pretreatment value. Nylidrin induced no change in the output of prostacyclin and thromboxane [A.sub.2] metabolites. CONCLUSION: Threatened preterm labor is associated with a use in prostacyclin and thromboxane [A.sub.2] synthesis. Indomethacin inhibits more thromboxane [A.sub.2] than does prostacyclin synthesis. These findings may explain the fetal vascular changes during maternal indomethacin treatment. (Am J Obstet Gynecol 1992; 166:150-4.)

The etiology of primary dysmenorrhea, which is the most common gynecologic complaint and cause of lost working hours, remains obscure but merits careful scientific investigation. Recent studies suggest that increased endometrial prostaglandin production and release may be responsible for dysmenorrhea. Prostaglandins cause myometrial contractility that, if excessive, leads to uterine ischemia and pain. This hypothesis has led to clinical trials of antiprostaglandin agents such as indomethacin and fenamates, which inhibit the synthesis of prostaglandin through the prostaglandin synthetase system as well as antagonize their action at the cell receptor level. The good response of dysmenorrhea to other conventional forms of therapy such as oral contraceptives and dilatation of the cervix can be partly explained on the basis of a reduced level of prostaglandins in the menstrual fluid with such therapy. There is a definite need for further evaluation of the antiprostaglandin compounds in the treatment of dysmenorrhea so that sound formulations can be evolved for the elimination of this incapacitating disorder.

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 F1α(6-keto-PGF1αand thromboxane B2(TxB2), respectively, from plasma. In addition, the capacity of the platelets to produce TxB2during spontaneous clotting was studied by measuring the TxB2levels from the serum incubated at +37°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-PGF1αin women with combined oral contraceptives (65.5 ± 16.1 pg/ml, mean ± SD) was lower (p < 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 TxB2levels in plasma or serum. In women with progestogen-only oral contraceptives, the plasma levels of 6-keto-PGF1αand TxB2were normal, but the capacity of the platelets to release TxB2during spontaneous clotting was decreased (113.6 ± 77.6 ng/ml versus 179.9 ± 81.9 ng/ml, p < 0.05). In a prospective trial on 11 women, who started using 30 μg of ethinyl estradiol and 150 μg of levonorgestrel, no changes in PGI2or TxA2were seen during the first 3 months of usage. The decrease in antiaggregatory PGI2during the prolonged use of estrogen-containing oral contraceptives may be associated with the increased risk of thromboembolism.