The effect of RU486 administered during the proliferative and secretory phase of the cycle on the bleeding pattern, hormonal parameters and the endometrium

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P₂-G), oestrone glucuronide (E₁-G), oestradiol (E₂), progesterone (P₄), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment. In four of these women the bleeding was scanty and followed by a menstrual-like bleeding at expected time, while in the remaining five volunteers the treatment bleeding was heavier and not followed by a new bleeding until a month later. The duration of the secretory phase was 16.5 ± 1.3 days in women with two bleeding episodes and 11.8 ± 1.9 days in women with one bleeding episode (P < 0.05). The hormonal parameters were similar in both groups up to the start of the treatment. In the patients with one bleeding episode, the treatment was associated with a reduction in progesterone concentration, while in the patients with two bleeding episodes the progesterone concentration remained elevated until the second bleeding episode. Light microscopic examination of the endometrium revealed unique changes in the endometrial morphology. The results indicate that RU486 acts mainly on the endometrium but a direct or indirect effect on the corpus luteum cannot be excluded. The age of the corpus luteum may be of importance for its susceptibility to RU486 treatment.