Antiprogestins: mechanism of action and contraceptive potential.
Antiprogestins are characterized by substitutions at the 11 beta and 17 alpha positions of the steroid ring system and bind strongly to both progesterone and glucocorticoid receptors. Although they function predominantly as antiprogestins and antiglucocorticoids, on occasion they display progestin agonistic and even antiestrogenic properties. The most common clinical use of the antiprogestin mifepristone is to induce a medical abortion in the early stages of pregnancy. Progesterone maintains the endometrium, transforming it from a proliferative to a secretory state. It also facilitates the luteinizing hormone surge, which initiates ovulation. As a consequence, antiprogestins may also have contraceptive potential. Although antiprogestins do delay ovulation, this effect is inconsistent unless high doses are given, and under these circumstances, the antiprogestin effect is associated with unopposed estrogen action on the endometrium. Very low doses of antiprogestins do not affect hormonal secretion or ovulation or alter bleeding patterns, but they do have contraceptive potential by inducing profound alterations in endometrial morphology. Mifepristone is also a very effective and safe postcoital agent. This new class of pharmacological agents has numerous other gynecological and obstetrical indications, such as endometriosis, uterine myoma, and expulsion of the fetus in the case of fetal death in utero. Antiprogestins may also be used in the treatment of steroid-dependent tumors. There are also therapeutic implications consequent to their antiglucocorticoid properties.
Spitz
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Center for Biomedical Research, New York, New York 10021, USA.
Croxatto
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Robbins
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D000021:Abortifacient Agents, Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D003270:Contraceptive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003283:Contraceptives, Postcoital, Synthetic / Q000378:metabolism / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D015735:Mifepristone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000021:Abortifacient Agents, Steroidal; D003270:Contraceptive Agents; D003283:Contraceptives, Postcoital, Synthetic; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D015735:Mifepristone; D007986:Luteinizing Hormone