Clinical Applications of Progesterone Receptor Antagonists and Selective Progesterone Receptor Modulators

Abstract

Since the description of the structure of the first progesterone receptor antagonist, mifepristone, was published, numerous related compounds have been synthesized, which may function as progesterone receptor antagonists (PRAs) or selective progesterone receptor modulators (SPRMs). The latter may be defined as a class of progesterone receptor ligands that exert clinically relevant tissue-selective full or partial progesterone agonist and antagonist effects on various progesterone target tissues in an in vivo situation depending on the biologic action studied. Mifepristone is a classic example of a PRA, whereas asoprisnil is an example of a SPRM. Short-term clinical applications of mifepristone include termination of first- and second-trimester pregnancy, early fetal demise (presence of nonviable embryo/fetus), and fetal death. It is also an excellent emergency contraceptive and can be used for menstrual regulation in women with menses delay. When given long-term, many PRAs and SPRMs display antiproliferative effects in the endometrium, and they are also associated with amenorrhea. Serum estradiol levels, however, remain in the early to midfollicular phase range. Because of their antiproliferative and progestin–antagonist action, PRAs and SPRMs have application in the treatment of uterine myoma and endometriosis without being associated with hypoestrogenism and its adverse consequences. Mifepristone has also been shown to have contraceptive potential by blocking the luteinizing hormone surge. It also reduces bleeding in progestin-only contraception.