Dose-dependent suppression of gonadotropins and ovarian hormones by elagolix in healthy premenopausal women
Abstract
Context: Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. Objective: We evaluated the pharmacokinetics and pharmacodynamics of elagolix. Design, Setting, and Participants: This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Interventions: Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main Outcome Measures: Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Results: Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Conclusions: Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women.
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Elagolix is rapidly absorbed after oral administration and its mean plasma half-life ranges from 2.4 to 6.3 h.
“Elagolix is rapidly absorbed after oral administration and its mean plasma half-life (t1/2) ranges from 2.4 to 6.3 h [99,107,110].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [99]
Elagolix is mainly metabolized by the liver, mostly by CYP3A, and 90% of excretion of elagolix and its metabolites occurs in the feces.
“It is mainly metabolized by the liver (mostly cytochrome P450 3A (CYP3A)-mediated), and 90% of excretion of elagolix and its metabolites occurs in the feces [99].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [99]
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- Authors
- Ng, J., Chwalisz, K., Carter, D. C., & Klein, C. E.
- Affiliations
- AbbVie (United States) (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-02-16
- Volume
- 102
- Issue
- 5
- Pages
- 1683-1691
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2610244466
- Cited by
- 110
- References
- 22
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 10 · 2021: 19 · 2020: 16 · 2019: 12 · 2018: 8 · 2017: 8
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- elagolix, GnRH antagonist, pharmacokinetics, pharmacodynamics, gonadotropin suppression, follicle-stimulating hormone, luteinizing hormone, estradiol suppression, progesterone, dose-dependent effects, premenopausal women, adverse events
- MeSH terms
- Adult, Dose-Response Relationship, Drug, Double-Blind Method, Estradiol, Female, Follicle Stimulating Hormone, Hormone Antagonists, Humans, Hydrocarbons, Fluorinated, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Middle Aged, Progesterone, Pyrimidines, Premenopause, Young Adult, Healthy Volunteers
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