Elagolix
Elagolix is an orally active, non-peptide GnRH antagonist for management of endometriosis-associated pain and, combined with add-back hormones, heavy menstrual bleeding from uterine fibroids. Being oral and dose-tunable, it produces partial-to-full estrogen suppression without an agonist flare.
01 Overview
Elagolix is a small-molecule GnRH receptor antagonist, distinct from the injectable peptide antagonists. Taken by mouth, it lowers LH, FSH, and estradiol in a dose-dependent way, letting clinicians titrate the degree of estrogen suppression.
It is approved for endometriosis pain (as Orilissa) and, co-formulated with estradiol/norethindrone add-back (Oriahnn), for fibroid-related bleeding. Add-back limits the bone-loss and vasomotor effects of estrogen deprivation.
02 Mechanism
Competitive non-peptide antagonism of the pituitary GnRH receptor dose-dependently suppresses LH/FSH and thus ovarian estradiol.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Endometriosis (lower dose) | 150 mg/day | Oral | 150 mg once daily, up to 24 months |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced endometriosis painSignificantly reduces dysmenorrhea and non-menstrual pelvic pain versus placebo. | Clinical | ||
| Dose-tunable estrogen suppressionOral dosing allows partial or near-full estradiol suppression as needed. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Hot flushes and vasomotor symptomsFlushing and night sweats increase with dose and duration. | Moderate | Very common | Clinical | |
| Bone mineral density lossReduced BMD limits high-dose therapy to 6 months without add-back. | Moderate | Common (dose/time dependent) | Clinical |