Role of progesterone antagonists and new selective progesterone receptor modulators in reproductive health

Given the importance of progesterone in female reproductive health, it was inevitable that analogues of this molecule would be developed to treat a variety of gynecologic maladies. Such medications, termed progesterone antagonists, act to counteract the effect of progesterone. A newer class of molecules, the selective progesterone receptor modulators (SPRMs), have both agonist and antagonist activities depending upon the site of action. These compounds have been studied for their effect on endometrial growth, endometrial vascular development, the hypothalmic-pituitary-ovarian axis and cervical integrity. Such research has led to a number of potential clinical applications. Progesterone antagonists are well established in their use for termination of pregnancy, although SPRMs seem to have a diminished capacity for induction of abortion. Similarly, antagonists work well to soften and dilate the cervix before surgery, but such efficacy by SPRMs is unlikely. Other applications for progesterone antagonists include induction of labor, the treatment of endometriosis, fibroids and contraception; SPRMs also may prove useful in the treatment of endometriosis and fibroids, as well as for postmenopausal hormone replacement therapy and the treatment of dysfunctional uterine bleeding. Finally, these compounds may aid investigators in unraveling many of the nuances of the role of progesterone in reproductive function.

Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the receptor action and selective modulation of progesterone, explain the effects of progesterone receptor modulators, and list the potential clinical applications of progesterone antagonists and selective progesterone receptor modulators.