No abstract

Clinical experience has indicated that the effects of RU 486 can be divided into dose-dependent and dose-independent effects. Examples of the dose-dependent effects include the antiglucocorticoid effects of RU 486, whereas pregnancy termination or dilatation of the cervix can be considered dose-independent with the various regimens tested so far. Following oral intake in man, the serum levels of RU 486 are in the micromolar range, and the half-life is approximately 30 hours. The concentrations of RU 486 in myometrial tissue are approximately one-third of those measured in serum. However, due to saturation of alpha 1-acid glycoprotein (AAG), the serum binding protein for RU 486, the serum levels remain similar within the dose range of 100-800 mg of RU 486. The unbound RU 486 is metabolized by two-step demethylation or by hydroxylation. The demethylated and hydroxylated metabolites of RU 486 retain considerable affinities of 9-21% towards the human progesterone receptor, and 45-61% towards the human glucocorticoid receptor (RU 486 = 100%), suggesting a biological role for the metabolites. Rat serum lacks a specific binding protein for RU 486. Even though the levels of RU 486 in rat adipose tissue are 40 times as high as those seen in serum, the concentrations of RU 486 in rat brain are only 28% of the serum levels. This indicates that diffusion of RU 486 into the central nervous system is restricted by the blood-brain barrier. Hence, the dose-dependency of certain centrally mediated effects of RU 486 might be explained by the limited diffusion of RU 486 into hypothalamic/hypophyseal sites, which seem to be reached only after ingestion of high doses of RU 486. However, the peripheral effects of RU 486, such as termination of pregnancy, are mediated via steroid receptors in target tissues. This suggests that similar biological effects can be attained at considerably lower doses than the ones currently in use.

A rare case of a twin pregnancy with a fetus in each half of a uterus didelphys (double uterus, double cervix and septate vagina) is reported. A longitudinal vaginal septum and two portios were detected during the first labor of this patient. During her second pregnancy ultrasonography was performed in the 16th week, and pregnancy was detected in each half of the double uterus. Both fetuses were of similar size and corresponded to the gestational age. A completely separated double uterus was confirmed by ultrasonography. In the 38th week a female and a male infant were delivered by cesarean section. The follow-up of this pregnancy and the management of the labor are reported.

No abstract

The results of several studies have suggested an inhibitory effect of the antiprogestin RU486 on late stages of folliculogenesis and ovulation. To assess the feasibility of using this property to inhibit ovulation without losing cycle control, an intermittent administration of RU486 alternated with medroxyprogesterone acetate (MPA) was tested in a phase I study. RU486 at a dose of 50 mg/day was given on menstrual cycle days 9-11 and 27-29, and 10 mg/day of MPA was given on cycle days 17-26 for three consecutive cycles to six Finnish and five Chilean women. Blood samples were collected two to three times a week for serum progesterone and oestradiol assays in three treatment cycles. One control cycle and one post-treatment recovery cycle were also monitored by serum samplings. Ultrasonography was carried out to measure follicular diameters in the treatment cycles. In 29 of 32 cycles, bleeding commenced within 3 days after the last MPA pill intake. Out of 32 treatment cycles, 20 were without luteal activity (serum progesterone < 9 nmol/l). Although 12 treatment cycles showed luteal activity (serum progesterone > or = 9 nmol/l), a clear rupture of a pre-ovulatory follicle > 15 mm, verified by ultrasonography, was seen in only one treatment cycle. During the treatment cycles with luteal activity (serum progesterone levels > or = 9 nmol/l), serum oestradiol concentrations were significantly higher on cycle days 9-18 and significantly lower at the end of the cycle compared with the cycles without luteal activity.(ABSTRACT TRUNCATED AT 250 WORDS)