Progesterone receptor modulators and progesterone antagonists in women’s health

Abstract

Both progesterone receptor modulators (PRMs) as well as pure progesterone antagonists (PAs) have numerous proven and potential therapeutic applications in female health care. Mifepristone, a PRM with only marginal agonistic activity, together with a prostaglandin can terminate pregnancies of less than 9 weeks duration; mifepristone is also used in the preparation of women at later gestational stages whose pregnancies are terminated with prostaglandins or surgery. Mifepristone causes expulsion of the uterine contents following intrauterine fetal death and promotes dilation of the non-pregnant primigravid uterus. It is also effective in the treatment of missed abortion. Together with methotrexate, mifepristone can be used in the medical treatment of ectopic pregnancy. Both PAs and PRMs display antiproliferative effects on the endometrium. Because of this, they have application in the treatment of endometriosis, an estrogen-dependent condition. They may also be utilized to reduce myoma size, acting as both a PA and antiproliferative agent. Unlike GnRH agonists, long-term use in endometriosis and myoma is not associated with loss of bone and hypoestrogenism. PRMs may also be useful in IVF programs to prevent a premature LH surge and to delay the emergence of the implantation window. Some PRMs have potential use as hormone replacement therapy in women during menopause or in those with dysfunctional uterine bleeding.