Linzagolix
Linzagolix is an oral, non-peptide GnRH antagonist approved in Europe for uterine fibroids and studied for endometriosis. Its distinguishing feature is a low dose that gives partial estrogen suppression usable without add-back, plus a higher dose with add-back for greater effect.
01 Overview
Linzagolix is a small-molecule GnRH receptor antagonist taken once daily. It was designed for flexible dosing: a lower dose achieves partial estradiol suppression that controls bleeding while limiting bone loss, potentially allowing therapy without hormonal add-back, while a higher dose with add-back gives stronger symptom control.
It is approved in the EU (Yselty) for heavy menstrual bleeding due to uterine fibroids and has been evaluated in endometriosis trials.
02 Mechanism
Oral non-peptide antagonism of the pituitary GnRH receptor dose-dependently suppresses LH/FSH and ovarian estradiol.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Low dose (no add-back) | 100 mg/day | Oral | 100 mg once daily for partial suppression |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced fibroid bleedingSignificantly reduces heavy menstrual bleeding from uterine fibroids versus placebo. | Clinical | ||
| Tunable estrogen suppressionLow dose enables partial suppression aimed at limiting bone loss without add-back. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Hot flushesVasomotor symptoms rise with dose, more frequent at 200 mg without add-back. | Moderate | Common (dose-dependent) | Clinical | |
| Bone mineral density reductionBMD decline at higher doses without add-back. | Moderate | Dose/time dependent | Clinical |