Clinical Applications of Mifepristone (RU486) and Other Antiprogestins Assessing the Science and Recommending a Research Agenda (1993) / Chapter Skim
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B3. The Use of Antiprogestins in the Reproductive Cycle
B3. The Use of Antiprogestins in the Reproductive Cycle
Pages 139-147
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From page 139... ...
This paper introduces the use of antiprogestins to alter the reproductive cycle of women, and reviews the published literature regarding such use in the follicular phase of the menstrual cycle. Although a number of such compounds exist, only RU 486 has been studied for these properties in clinical trials.
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From page 140... ...
Given the importance of progesterone to female reproductive competence, the availability of progesterone antagonists was hailed as providing new venues for exploration of progesterone action and for treatment of progesterone-dependent conditions. Much of this speculation was based on the assumption that progesterone antagonists would simply reverse or inhibit progesterone actions.
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From page 141... ...
These compounds may be useful in induction of lactation and may have intriguing effects on polycystic ovary syndrome, although such potential actions have not been formally evaluated. The treatment regimens used to test the potential of RU 486 as a contraceptive agent are logical extensions of the dose-response effects at various times in the menstrual cycle.
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From page 142... ...
This effect is dose dependent: lower doses (25 mg on days 1-14 or 50 mg/day on days 7-10) allow continued follicular growth, accompanied by lower than normal daily increments in serum estrogen and a delay in the LH surge until after discontinuation of the agent (Luukkainen et al., 1988; Swahn et al., 1988~.
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From page 143... ...
At lower doses, luteolysis is not achieved consistently with endometrial shedding, and another bleeding episode is commonly observed within two weeks when estrogen and progesterone levels fall to the follicular phase range. Presumably, this second bleeding reflects regrowth of the endometrium under the influence of continued corpus luteum function and subsequent shedding as luteolysis occurs.
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From page 144... ...
The amount of estrogen produced must be adequate to maintain bone mass, normal lipid profiles, and sexual function. However, if this estrogen level is achieved, some women are likely to develop endometrial hyperplasia because progesterone levels may not be sufficient to transform adequately the endometrium.
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From page 146... ...
Daily administration of the progesterone antagonist RU 486 prevents implantation in the cycling guinea pig. American Journal of Obstetrics and Gynecology 165:82 86, 1991.
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From page 147... ...
Antiprogestin treatment decreases midluteal luteinizing hormone pulse amplitude and primarily exerts a pituitary inhibition. American Journal of Obstetrics and Gynecology 163:1982-1985, 1990.
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