The effect of RU 486 administered during the early luteal phase on bleeding pattern, hormonal parameters and endometrium

Abstract

The purpose of the present study was to investigate the effect of a single dose of RU 486 administered very early in the secretory phase on endometrial development and levels of progesterone receptors, on plasma levels of gonadotrophins and ovarian hormones and on the pattern of menstrual bleeding. Twenty-four regularly menstruating subjects participated and were studied during a control, a treatment and a follow-up cycle. In the treatment cycle, a single dose of 200 mg RU 486 was given in the evening of the second day after the urinary LH peak. Plasma was collected from cycle day 10 until menstruation in both control and treatment cycles. The lengths of the control, treatment and follow-up cycles were equal. Three of the subjects had slight vaginal bleeding in association with RU 486 intake which, however, did not disturb their normal menstrual rhythm. Plasma levels of oestradiol, progesterone and FSH were not affected in the treatment cycle, whereas LH levels increased slightly. The elimination half-life of RU 486 was 28.6 h. An endometrial biopsy was taken 12, 36 or 84 h (LH + 3, LH + 4 and LH + 6) after drug intake (eight subjects in each group) and another biopsy was taken on the corresponding day in the control cycle. The specimens were assessed by morphometric analysis and for cytosolic progesterone receptor concentrations. Endometrial biopsies taken 12 h (on LH + 3) after RU 486 intake contained significantly (P less than 0.001) lower levels of cytosolic progesterone receptors than in the control cycle, but levels at 36 and 84 h were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium

“…All P 4 serum levels obtained on LHC7 were within expected values for a spontaneous normal menstrual cycle (O30 nmol/l) with no statistically significant differences between the mifepristone-and placebotreated groups (Table 1) in agreement with previous reports (Swahn et al 1990). No unscheduled bleeding or spotting was reported.…”

“…After 5 days of mifepristone administration is difficult to speculate about the proportion of PGRs that remain blocked in the endometrium since to our knowledge there is no report regarding this matter so far. The studies performed with mifepristone administration during the early luteal phase showed an out-of-phase endometrial development in spite of high circulating P 4 , suggesting a persistent block of the PGR (Swahn et al 1990). The administration of mifepristone (200 mg) in LHC2 reaches a peak circulating level of w0.3-0.4 mmol/l within 2 h (Sarkar 2002) and is able to alter uterine gene expression in early pregnancy as early as 6 h after oral administration (Critchley et al 1996).…”

“…Under these circumstances, P 4 had already started to exert its effects in the endometrium and mifepristone induces menses within 48 h. Hence, the block of P 4 action during mid-secretory phase not only renders the endometrium unreceptive but also induces processes involved in menstruation generating a confounding effect that difficult the identification of transcripts involved in endometrial receptivity. When mifepristone is administered immediately after ovulation, the length of the menstrual cycle and plasmatic levels of estradiol and P 4 are not affected (Swahn et al 1990), however induces a dramatic effect on endometrial development (Dockery et al 1997, Danielsson et al 2003. For these reasons we chose for the present study, administering mifepristone on the Enriched functional annotations found in GATHER (Table 7) and Database for Annotation, Visualization and Integrated Discovery (Table 8) appear in bold.…”

“…When a single dose of mifepristone (200 mg) is administered 2 days after ovulation (i.e. 2 days after the LH surge, LHC2) affects neither the menstrual cycle length nor serum estrogen and P 4 levels, however it profoundly affects endometrial morphology, retarding endometrial development and inhibiting the glandular secretory activity (Swahn et al 1990) which ultimately prevents pregnancy (GemzellDanielsson et al 1993, Hapangama et al 2001. Gemzell- reported the contraceptive effects of a single dose of mifepristone 200 mg in LHC2 to a group of women as their only contraceptive method.…”

Clinical Research on Efficacy of Cassia Twig Tuckahoe Capsule and Mifepristone Combined with Laparoscopic Surgery for the Treatment of Endometriosis

“…Other study also reported a higher pregnancy rate in Cassia twig Tuckahoe capsule group, 5 out of 10 endometriosis patients with infertility were pregnant in comparison to mifepristone [26]. Mifepristone decreases estrogen, progesterone, luteinizing hormone and makes endometrial incapable for implantation which is against pregnancy [27] [28] [29].…”