1 Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide GnRH Antagonist Elagolix Abbreviated Title: HPG Suppression by an Oral Nonpeptide GnRH Antagonist R. Scott Struthers, Andrew J. Nicholls, John Grundy, Takung Chen, Roland Jimenez, Samuel S.C. Yen*, Haig P. Bozigian Neurocrine Biosciences Inc.(R.S.S., A.N., J.G., T.C., R.J., H.P.B), 12790 El Camino Real, San Diego, California 92130 and Department of Reproductive Medicine (S.C.C.Y.), University of California, San Diego Corresponding Author & to whom reprint requests should be addressed: R. Scott Struthers: Neurocrine Biosciences Inc., 12780 El Camino Real, San Diego, CA 92130. Tel: 858-617-7740; Fax 858-617-7696; E-mail: sstruthers@neurocrine.com Disclosure summary: R.S.S., A.N., J.G., T.C., R.J., H.P.B are, or were, employees of Neurocrine Biosciences and have, or had, equity interests in the company. S.C.C.Y. consulted for, and had equity interests in, Neurocrine Biosciences. * We wish dedicate this work to our friend, mentor, and co-author, Dr. Sam Yen who did not live to see a complete draft of this manuscript. While many of the designs, insights and data analysis presented here are his, the remaining limitations and flaws in this manuscript would not have escaped his attentions. Support : This work was supported, in part, by National Institutes of Health grants 1-R43-HD38625- 01 and 2-R44-HD38625-02. "This is an un-copyedited author manuscript copyrighted by The Endocrine Society. This may not be duplicated or reproduced, other than for personal use or within the rule of “Fair Use of Copyrighted Materials” (section 107, Title 17, U.S. Code) without permission of the copyright owner, The Endocrine Society. From the time of acceptance following peer review, the full text of this manuscript is made freely available by The Endocrine Society at http://www.endojournals.org/ . The final copy edited article can be found at http://www.endojournals.org/ . The Endocrine Society disclaims any responsibility or liability for errors or omissions in this version of the manuscript or in any version derived from it by the National Institutes of Health or other parties. The citation of this article must include the following information: author(s), article title, journal title, year of publication and DOI.” Précis: Oral administration of the nonpeptide GnRH antagonist, elagolix, to premenopausal women results in transient suppression of gonadotropins, and more sustained suppression of estradiol. Word Count: 3754; Tables: 3; Figures: 3. J Clin Endocrin Metab. First published ahead of print November 25, 2008 as doi:10.1210/jc.2008-1695 Copyright (C) 2008 by The Endocrine Society