Progesterone-receptor modulators (PRMs) are progesterone-receptor ligands that can exert agonistic, antagonistic or mixed agonist-antagonist effects depending on the cellular context. The mechanisms of action of these compounds are still incompletely understood. PRMs already have several applications in women's health such as emergency contraception, pregnancy termination, management of early fetal demise and cervical maturation. The main indications that will be developed in the future include dysfunctional bleeding and preoperative treatment of uterine myomas. Other future indications may include estrogen-free contraception, treatment of endometriosis and prevention and treatment of breast cancer. However, the available data from mid- to long-term continuous administration studies has raised the issue of endometrial safety. For this reason, long-term applications of PRMs are currently postponed, although windows of treatment with a short course of progestin therapy, or even by a short interruption of treatment, could improve endometrial aspects if needed.
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