Effects of progesterone antagonist ZK 98.299 on early pregnancy and foetal outcome in bonnet monkeys.

The antiprogestin ZK 98.299 (onapristone) was injected subcutaneously (25 mg/day) for 4 consecutive days during early pregnancy to 8 bonnet monkeys. Retrospective analysis of the data showed that the treatment was initiated between 20 to 30 days after the mid-cycle peak in estradiol levels. In 7 animals, vaginal bleeding was induced within 3.6 +/- 2.7 days (mean +/- S.D.) after the initiation of treatment. However, pregnancy was terminated completely only in 5 animals. In these 5 animals, menstruation was induced 1 to 4 days after the initiation of treatment. Serum progesterone levels also decreased; however, a significant decrease (p less than 0.02) in mean levels was not observed until 5 days after the initiation of treatment. In the other 3 animals, in spite of some drop in serum progesterone levels after the treatment and slight vaginal bleeding in 2 animals, the pregnancy continued. Two animals delivered stillborn foetuses at term. The foetuses weighed 92 and 105 g, which is markedly lower than the normal foetal weight (345 +/- 48 g, n = 6) at birth. The gross appearance of the foetuses was suggestive of recent intrauterine foetal death. In the third animal hysterotomy was performed on day 65; foetus weighed 5 g. Haematoma and blood clots were seen in the placental tissue. This limited data on 8 animals demonstrates that ZK 98.299, at the dose regimen employed, completely terminates early pregnancy in 62% of animals. In the cases in which treatment failed, the pregnancy did not continue unaffected. The endocrine function of the placenta was affected and the foetal growth was retarded.(ABSTRACT TRUNCATED AT 250 WORDS)