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  • Title: Mechanism of action and clinical effects of antiprogestins on the non-pregnant uterus.
    Author: Spitz IM, Robbins A.
    Journal: Hum Reprod Update; 1998; 4(5):584-93. PubMed ID: 10027612.
    Abstract:
    Considerable progress has been made in elucidating the mechanism of action of antiprogestins. The biological response to a progesterone antagonist depends on many factors. The usual effect is that of an antagonist, but progesterone agnostic or even antioestrogenic or oestrogenic effects have also been observed. The present review focuses on the clinical applications of antiprogestins in the non-pregnant uterus. Whereas high doses of antiprogestins block ovulation, low doses impair endometrial development without affecting ovulation, hormonal levels or bleeding patterns Indeed, the endometrium is the tissue which is the most sensitive to antiprogestins. The effect of antiprogestins is to produce a delay in endometrial maturation and to postpone the appearance of the implantation window. This concept of 'endometrial contraception' requires further testing in humans, although the principle has been proven in monkeys. In contrast to the low doses of mifepristone which delay endometrial maturation, a minimum dose of 50 mg is required to produce endometrial bleeding. Late luteal phase antiprogestin administration does not disturb ovulation, hormonal levels or bleeding patterns. This has clinical application, and mifepristone has been used together with prostaglandins in women with delayed menses to successfully prevent implantation. Mifepristone has also been shown to be an effective post-coital agent. However, when used on a regular basis once monthly at the end of the cycle as a potential contraceptive, the results are disappointing. Because of their antiproliferative and anti-oestrogenic effects on the endometrium, antiprogestins are also used in the treatment of oestrogen-dependent conditions such as endometriosis and fibromyomas. In humans, chronic administration of high doses of antiprogestins has on rare occasions been associated with endometrial hyperplasia, presumably a consequence of unopposed oestrogen activity. This does not occur with low doses (1 mg daily for 5 months).
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