Regulation of human endometrial function: mechanisms relevant to uterine bleeding

This review focuses on the complex events that occur in the endometrium after progesterone is withdrawn (or blocked) and menstrual bleeding ensues. A detailed understanding of these local mechanisms will enhance our knowledge of disturbed endometrial/uterine function – including problems with excessively heavy menstrual bleeding, endometriosis and breakthrough bleeding with progestin only contraception. The development of novel strategies to manage these clinically significant problems depends on such new understanding as does the development of new contraceptives which avoid the endometrial side effect of breakthrough bleeding

The possible use of antiprogestins for contraception

BACKGROUND: A number of compounds, antiprogestins, e.g. mifepristone, onapristone and lilopristone, have been developed which compete with progesterone at the receptor level. One of these, mifepristone, is in combination with a prostaglandin analogue currently in use for termination of early pregnancy. The possibility to use these compounds for contraceptive purposes is presently under evaluation. METHODS: The possible contraceptive effect of antiprogestins has been evaluated in both clinical and experimental studies. RESULTS: Administration of antiprogestin during the follicular phase has an inhibitory effect on follicular development and ovulation, and on endometrial development and function if administered during the secretory phase of the menstrual cycle. A high dose of mifepristone, 200 mg, administered immediately following ovulation is highly effective in preventing implantation, most likely due to an effect on endometrial receptivity. It seems that the endometrium is more sensitive to antiprogestin than is the ovulatory process. Low weekly, 2.5 mg to 5 mg, and daily doses, 0.5 mg, of mifepristone did not inhibit ovulation, but a significant effect on endometrial development and especially endometrial function judged from measurement of the expression of a number of markers for endometrial receptivity could be demonstrated. CONCLUSION: The effect of mifepristone on the endometrium may be sufficient to prevent implantation, and if so, an oral contraceptive method could be developed which has no effect on ovarian function

Contraception with anti-progesterone

Anti-progesterones have potential as contraceptives, acting either by the inhibition of ovulation or the inhibition of endometrial development. Clinical studies have shown that once-a-month treatment with Mifepristone in the early luteal phase is an effective contraceptive method, and that emergency post-coital contraception with Mifepristone is at least as effective as other methods currently used. Recent studies indicate that the endometrium is more susceptible to Mifepristone than are the hypothalamic and pituitary regions, and it may therefore be possible to develop a new contraceptive method based on low daily or once-weekly doses of Mifepristone that does not influence ovarian function