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Extending the interval of action and effectiveness of the emergency contraceptive ulipristal acetate

Jon Hennebold, Oregon National Primate Center/Oregon Health & Science University, 2013

Project abstract

Emergency contraception (EC) provides an option for women at risk for unintended pregnancy, including those that had intercourse without using any contraceptive method, those noting failure of their primary contraceptive method, and victims of sexual assault. The use of EC has risen steadily over the past decade such that 10% of sexually active women have reported using it at least once per year.

Ulipristal acetate (UPA; brand name ella), a progesterone receptor antagonist that functions by inhibiting follicle rupture and release of a fertilizable egg, has emerged as an effective EC that prevents pregnancy even when taken five days after intercourse. At present, however, there are significant gaps in our understanding of 1) why EC effectiveness drops dramatically when administered during or after the midcycle ovulatory luteinizing hormone (LH) surge, and 2) whether progestin-containing contraceptives initiated or re-started immediately following the use of UPA limit its action. With regard to the former, we have preliminary evidence that the midcycle LH surge induces the expression of an enzyme within the ovulatory follicle that likely degrades UPA, possibly preventing it from inhibiting ovulation as well oocyte fertilization and embryo implantation. Concerning the latter, the lack of empirical evidence is currently a major roadblock in determining when to use hormonal contraception following UPA ingestion.

Thus, the molecular/biochemical studies outlined in this proposal will address the mechanism through which UPA efficacy diminishes post-LH surge, which in turn may lead to strategies whereby its contraceptive potential could be extended through the periovulatory interval into the period of implantation. Moreover, the proposed clinical studies will help define the interval when hormonal contraceptives can be started following the use of UPA as an EC. Collectively, these studies will provide valuable information that is necessary for optimizing EC efficiency and preventing unintended pregnancies.


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