Pharmacokinetic considerations for gonadotropin-releasing hormone agonists and antagonists to treat endometriosis

Anna Maria Paoletti, Manuela Neri, Monica Pilloni, Maria Francesca Marotto, Elena Giancane, Valerio Vallerino, Bruno Piras, Giulia Melis, Virginia Melis, Michele Danilo Maria Masciale, Enrica Murgia, E. Murgia, Gian Benedetto Melis
Expert opinion on drug metabolism & toxicology · 2025 · vol. 21(6) , pp. 649–663 · doi:10.1080/17425255.2025.2499550 · PMID:40315284 · W4410027033
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This review discusses the pharmacokinetic properties of GnRH agonists and antagonists, highlighting that non-peptide GnRH antagonists offer faster action and oral administration for endometriosis treatment.

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Abstract

INTRODUCTION: Endometriosis is a chronic disease characterized by endometriotic cells implanted outside the uterus triggering a chronic inflammatory state. Estradiol stimulates the endometriotic implants, which overexpress estrogen receptor β. Lowering estradiol levels to a range within 40-50 pg/ml allows antagonizing the growth of endometriotic implants and counteracting its-related disabling symptoms. AREAS COVERED: By blocking the Gonadotropin-Releasing-Hormone (GnRH) receptors, GnRHagonists, peptide GnRHantagonists, non-peptide GnRHantagonists induce hypoestrogenism, due to the suppression of pituitary gonadotropins. This manuscript provides the results of an electronic literature search on pharmacological features of GnRHagonists and GnRHantagonists to treat endometriosis. Hypoestrogenism-dependent side effects can be counteracted by concomitant estrogen and progestin compounds (add-back therapy). GnRHagonists chronic administration induces hypoestrogenism after 10-12 days, since initial administrations stimulate gonadotropin rise (flare-up effect). Peptide GnRHantagonists quickly block GnRH-receptors inducing an immediate hypoestrogenism. Similarly to GnRHagonists, their peptide structure impedes the oral administration. The non-peptide GnRHantagonists have the advantage both of being taken orally and inducing a rapid dose-dependent hypoestrogenism. EXPERT OPINION: GnRHagonists and peptide GnRHantagonists are effective to treat endometriosis, but require complex ways of administration. Non-peptide GnRHantagonists offer more important prospects in the tailored medical treatment of endometriosis, given their rapid onset of action and their oral way of administration.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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.

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Cited by (2)

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