Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

R Scott Struthers, Andrew J Nicholls, Andrew Nicholls, John S. Grundy, John Grundy, Takung Chen, Roland Jimenez, Samuel S C Yen, Haig P Bozigian, Haig Bozigian
The Journal of clinical endocrinology and metabolism · 2008 · vol. 94(2) , pp. 545–551 · doi:10.1210/jc.2008-1695 · PMID:19033369 · PMC2646513 · W2118330723
article OA: green CC0 ⤵ 64 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Oral administration of the nonpeptide GnRH antagonist elagolix rapidly suppressed gonadotropins and estradiol in healthy premenopausal women, with effects reversing upon discontinuation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

CONTEXT: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. OBJECTIVE: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. DESIGN: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. PARTICIPANTS: Fifty-five healthy, regularly cycling premenopausal women participated. INTERVENTIONS: Subjects were administered a single oral dose of 25-400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (+/-1) after onset of menses. MAIN OUTCOME MEASURES: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. RESULTS: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 +/- 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. CONCLUSIONS: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Estradiol Gonadotropin-Releasing Hormone Gonadotropins Hormone Antagonists Hydrocarbons, Fluorinated Pyrimidines Administration, Oral Adolescent Adult Dose-Response Relationship, Drug Double-Blind Method Down-Regulation Down-Regulation Estradiol Estradiol Female Gonadotropin-Releasing Hormone Gonadotropins Gonadotropins Gonads

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (28)

Cited by (50)

Source provenance

europepmc
last seen: 2026-06-22T06:15:23.361955+00:00
openalex
last seen: 2026-05-10T11:47:08.515417+00:00
pubmed
last seen: 2026-05-13T22:14:18.065553+00:00
License: CC0 · commercial use OK