Selective progesterone receptor modulators and reproductive health.

Abstract

This review is intended to provide perspective on the history of selective progesterone receptor modulators (SPRMs) and progesterone antagonists, their current availability, therapeutic promise and safety concerns. Despite keen interest in synthesis of these compounds, only a handful have had clinical test results allowing for commercialization. Mifepristone is well tolerated and effective for single dose first trimester at-home pregnancy termination and is available in much of the world. Ulipristal acetate, at single doses, is well tolerated and effective for emergency contraception, with less availability. Chronic use of these agents has been associated with abnormal liver enzymes, and rarely, with hepatic failure; causality is not understood. SPRMs and progesterone antagonists have great therapeutic promise for use in other reproductive disorders, including breast cancer, endometriosis, adenomyosis, estrogen-free contraception and cervical ripening but require additional study. Alternative formulations, whether local (topical breast or intrauterine) or extended-release may reduce the incidence of liver function abnormalities and should be explored.