Antiprogestins in gynecological diseases

Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g., menstrual regulation, emergency contraception, and termination of early pregnancies. These initial applications, however, belied the capacity for these compounds to interfere with cell growth. Within the context of gynecological diseases, antiprogestins can block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They can also interrupt the excessive growth of cells giving rise to benign gynecological diseases such as endometriosis and leiomyomata (uterine fibroids). In this article, we present a review of the literature providing support for the antigrowth activity that antiprogestins impose on cells in various gynecological diseases. We also provide a summary of the cellular and molecular mechanisms reported for these compounds that lead to cell growth inhibition and death. The preclinical knowledge gained during the past few years provides robust evidence to encourage the use of antiprogestins in order to alleviate the burden of gynecological diseases, either as monotherapies or as adjuvants of other therapies with the perspective of allowing for long-term treatments with tolerable side effects. The key to the clinical success of antiprogestins in this field probably lies in selecting those patients who will benefit from this therapy. This can be achieved by defining the genetic makeup required – within each particular gynecological disease – for attaining an objective response to antiprogestin-driven growth inhibition therapy. FREE SPANISH ABSTRACT: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/1/15/suppl/DC1.