Alteration of Lymphocyte Reactivity in Pregnant Women Treated With the Progesterone Receptor Inhibitor ZK 98734

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Abstract
Thirteen women during the 5th and 6th weeks of gestation were treated with a progesterone receptor blocker (ZK 98734) for pregnancy termination. Five patients received 100 mg/day of the compound, and eight patients received 50 mg/day for 4 days. Daily blood samples were obtained during the treatment period as well as on days 8 and 15 after the beginning of drug administration, and cytotoxic activity, progesterone sensitivity, and progesterone binding capacity of the lymphocytes were determined. Determination of SP-1 concentrations monitored the saturation state of trophoblastic progesterone receptors. High and low responders to the progesterone antagonist were identified. Lymphocytes of high responders treated with the 100 mg/day dose demonstrated a rapid increase of cytotoxicity, with a concomitant fall in progesterone sensitivity and progesterone binding capacity. Vaginal bleeding began as early as the 2nd day of treatment, and pregnancy was terminated by the 8th day of the treatment. Low responders receiving 100 mg/day demonstrated similar but attenuated changes. Low responders did not bleed during the first 4 days of treatment and termination of pregnancy occurred later compared to high responders. Lymphocytes of high responders treated with 50 mg/day behaved similarly to those obtained from the low responders treated with 100 mg/day, and abortion was not completed before the 25th day after the beginning of the treatment. Lymphocytes function of low responders treated with 50 mg/day did not change significantly, the SP-1 concentration did not decline, and pregnancies continued. We conclude that a difference in sensitivity to the progesterone receptor blocker explains the selective block at trophoblastic binding sites only and the inability to block those in the lymphocytes. Progesterone receptor blocker apparently discriminates between lymphocytic and trophoblastic binding sites. Lymphocytes progesterone binding sites block correlates better than does trophoblastic receptors block in the prediction of successful interruption of early pregnancies with ZK.