This study was designed to assess the features and conditions for endometrial bleeding induction with the synthetic antiprogestin and antiglucocorticoid RU 486 during hCG‐induced prolongation of the luteal phase. Eighteen healthy, surgically sterilized women and another five women with an intrauterine contraceptive device (IUD) participated. All subjects received hCG which was injected daily in increasing doses (500 to 15 000 IU) from day 9 to day 15 of the luteal phase. Ten subjects received hCG alone, and groups of three to 16 subjects received hCG combined with RU 486 (25, 50, 100,200 or 400 mg/day). RU 486 administration was commenced on day 12 following the LH surge and given either for 1, 4 or 7 consecutive days. In certain cycles, tamoxifen (20 mg/day) was given for 4 consecutive days with hCG, or with hCG and RU 486. All treatment cycles were separated by one or two resting cycles. Frequent blood samples were taken to monitor the endocrine response. Treatment with hCG alone or with the various combinations of RU 486 produced similar serum levels of oestradiol and progesterone which were equivalent to those observed during early pregnancy. With hCG alone, the onset of bleeding was on day 21–24 after the LH surge, coinciding with the drop in oestradiol and progesterone. With RU 486 doses of 50 mg/day or more, an early bleeding episode almost invariably occurred on day 14–17 after the LH surge in the presence of high circulating steroid levels. In contrast, 25 mg/day RU 486 for 4 days failed to induce this early onset of bleeding in three out of six cases. Tamoxifen did not cause early bleeding and failed to potentiate the effect of RU 486. In 43% of the cycles treated with RU 486, a second bleeding episode occurred on days 22–24 after the LH surge coincident with the drop of steroids. This late bleeding was less frequent (17%) in the subgroup receiving a total dose of 700 or 800 mg RU 486. In those cycles that exhibited a second bleeding episode coincident with the fall in progesterone, endometrial biopsies, taken shortly after the initial early bleeding had stopped, showed a mixed proliferative and secretory endometrium, suggestive of incomplete shedding. In contrast, only proliferative endometrium, compatible with complete shedding, was evident in cycles characterized by the absence of a second bleeding episode. It is concluded that during maintenance of corpus luteum function with exogenous hCG, RU 486 can induce endometrial bleeding despite high circulating progesterone and oestradiol levels. With the lower doses of RU 486 this bleeding is often accompanied by incomplete sloughing of the endometrium leading to a second bleeding episode at the time of corpus luteum demise.
|Number of pages||9|
|Publication status||Published - 1989|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism