TABLE B4.2 Concentration (pg/mg) of PGF2a and PGE2 in Endometrium Obtained from Women Who Received Mifepristone (5 mg/kg) in the Follicular (day 8–10) or Luteal (day 19–22) Phase of the Cycle, 24 Hours Prior to Sampling (N = 5–7 each group)


Follicular Phase


Luteal Phase








193 ± 37

515 ± 204

473 ± 49a

1458 ± 259a


310 ± 50

489 ± 80

433 ± 106

795 ± 211

a P 8 0.001, Mann-Whitney.

necrosis of the blood vessels (Li et al., 1988; Swahn et al., 1988). These latter changes are of particular interest because they occur in the decidua in early pregnancy after administration of mifepristone and are associated with the reduction in prostaglandin dehydrogenase in the vessel wall (Cheng et al., 1993a). At the same time there is a striking increase in the concentration of PGE2 as demonstrated by immunocytochemistry (Cheng et al., 1993b). Mifepristone increases the release of the prostaglandins PGF2a and PGE2 by dispersed endometrial cells cultured in vitro (Kelly et al., 1986), while the "concentration" of PGF2a is increased in endometrium recovered from women who had taken mifepristone (5 mg/kg) 24 hours previously (Table B4.2). Thus antigestogens may increase the effective local concentration of prostaglandins both by provoking their release and by inhibiting their local metabolism (Kelly and Buckman, 1990).

In summary, in the follicular phase of the cycle, mifepristone inhibits follicular development and ovulation through an effect on the secretion of gonadotropins but has little effect on the endometrium. Immediately after ovulation, mifepristone retards the development of a secretory endometrium by antagonizing the effect of progesterone. Late in the luteal phase, endometrial bleeding is provoked in a manner that simulates what occurs at menses after regression of the corpus luteum.

Although antigestogens do not bind to the estrogen receptor, both onapristone and mifepristone have the ability to antagonize the action of estrogen on the endometrium (van Uem et al., 1989). Endometrial atrophy occurs in castrate monkeys given mifepristone in combination with estrogen. The mechanism of this noncompetitive inhibition of estrogen is unknown but is associated with a striking up-regulation of the estrogen receptor (ER) (Neulen et al., 1990). Another antigestogen (onapristone) produces a similar noncompetitive inhibition of the effect of estrogen on the rabbit uterus (Chwalisz et al., 1991). The antagonism of estrogen is not due to binding to the ER. It is possible that the increase in ER after mifepristone is due to uncontrolled expression of ER, which

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement