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Elagolix

Elagolix

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Non-peptide oral GnRH receptor antagonist; FDA-approved for endometriosis pain (Orilissa) and heavy menstrual bleeding from uterine fibroids (Oriahnn). Included in this vault for educational completeness alongside peptide-based GnRH modulators.

Quick Facts

Property Value
Also Known As Orilissa, Oriahnn (combination), NBI-56418, ABT-620
Category GnRH Antagonist (Non-peptide) / Reproductive
Sequence N/A — Elagolix is a non-peptide small molecule, not a peptide. It is a uracil derivative that acts on the same GnRH receptor targeted by peptide GnRH agonists and antagonists.
Molecular Weight ~631.6 Da (as sodium salt)
Molecular Formula C32H30F5N3O5
PubChem CID 11289399
Administration Oral tablet
Typical Dose Range 150 mg once daily (lower dose) or 200 mg twice daily (higher dose) for endometriosis; 300 mg twice daily with add-back therapy for uterine fibroids
Half-Life ~4-6 hours
Storage Room temperature (20-25C)
FDA Status Approved (2018) — Orilissa for endometriosis-associated pain. Approved (2020) — Oriahnn (elagolix + estradiol + norethindrone acetate) for heavy menstrual bleeding associated with uterine fibroids.
WADA Status Not prohibited (FDA-approved medication)

Important Note: Elagolix is NOT a peptide. It is an orally bioavailable small molecule GnRH receptor antagonist. It is included in this vault alongside peptide-based GnRH modulators (Gonadorelin, Leuprolide, Goserelin, Triptorelin, Degarelix) for educational completeness, similar to how MK-677 (a non-peptide GHS-R agonist) is included alongside peptide growth hormone secretagogues.

Mechanism of Action

Elagolix is an orally bioavailable, non-peptide GnRH receptor antagonist that competitively blocks the GnRH receptor on anterior pituitary gonadotroph cells. By blocking endogenous GnRH signaling, elagolix produces dose-dependent suppression of LH and FSH, leading to reduced estradiol production from the ovaries.

A distinguishing pharmacological feature of elagolix is its short half-life (~4-6 hours), which enables dose-dependent, partial estrogen suppression rather than the complete suppression achieved by depot GnRH agonists. At the lower dose (150 mg QD), elagolix reduces estradiol to early follicular phase levels (partial suppression), preserving some estrogenic activity and reducing hypoestrogenic side effects. At the higher dose (200 mg BID), suppression is more complete but still allows some residual estrogen production (PMID: 28525302).

This dose-titratable, partial suppression model is a key clinical advantage over injectable GnRH agonists (leuprolide, goserelin), which produce near-complete estrogen suppression with inevitable bone loss and vasomotor symptoms. For uterine fibroids, elagolix is administered at the higher dose (300 mg BID) with hormonal add-back therapy (estradiol + norethindrone acetate) to maintain bone-protective estrogen levels while achieving adequate uterine fibroid symptom control (PMID: 31971678).

Key Research Areas

  1. Endometriosis pain (Elaris EM-I/II) — Two pivotal Phase III trials demonstrated significant reduction in dysmenorrhea (75.8% response at higher dose vs ~20% placebo) and nonmenstrual pelvic pain (PMID: 28525302)
  2. Uterine fibroids (Elaris UF-I/II) — Phase III trials showed elagolix + add-back therapy reduced heavy menstrual bleeding (68-76% response vs 9-10% placebo) while preserving bone density (PMID: 31971678)
  3. Dose-dependent estrogen suppression — Unique pharmacological profile allowing partial suppression at lower doses, enabling a "dial" approach to estrogen modulation
  4. Add-back therapy paradigm — Pioneered the combination of high-dose oral GnRH antagonism with hormonal add-back as a long-term treatment strategy for uterine fibroids

Evidence Level Summary

Evidence Type Count Notes
Systematic reviews 0 —
Human RCTs 2 Elaris EM-I/II (endometriosis); Elaris UF-I/II (uterine fibroids)
Human observational 0 —
Animal in vivo 0 —
In vitro 0 —

Clinical Applications

  • Endometriosis — First-line oral GnRH antagonist for moderate-to-severe endometriosis-associated pain (dysmenorrhea and nonmenstrual pelvic pain)
  • Uterine Fibroids — Heavy menstrual bleeding management as combination product (Oriahnn) with add-back therapy
  • Sexual Health — Ovarian hormone suppression for hormone-dependent gynecological conditions

Protocols Using This Peptide

  • No current vault protocols use elagolix (FDA-approved prescription medication, not a research peptide)

Ageless Peps Products

  • Not sold by Ageless Peps. Elagolix is an FDA-approved prescription medication (Orilissa/Oriahnn) available only through licensed pharmacies.

Dosing Reference

FDA-Approved Dosing

Indication Dose Route Frequency Duration Source
Endometriosis (moderate pain) 150 mg Oral Once daily Up to 24 months FDA label (Orilissa)
Endometriosis (severe pain) 200 mg Oral Twice daily Up to 6 months FDA label (Orilissa)
Uterine fibroids 300 mg (+ E2/NETA add-back) Oral Twice daily Up to 24 months FDA label (Oriahnn)

Cycling

Not applicable in the traditional peptide cycling sense. Treatment duration is limited based on dose level and bone density concerns: up to 24 months at 150 mg QD for endometriosis, up to 6 months at 200 mg BID without add-back, or up to 24 months at 300 mg BID with add-back therapy for fibroids. Bone mineral density should be monitored, particularly with higher doses and longer treatment.

Contraindications & Safety

  • Contraindications: Pregnancy (Category X — may cause early pregnancy loss), known osteoporosis, severe hepatic impairment (Child-Pugh C), concomitant use with strong OATP1B1 inhibitors (e.g., cyclosporine, gemfibrozil)
  • Common side effects: Hot flashes (24-46% dose-dependent), headache (17-20%), nausea (11%), insomnia, anxiety, arthralgia, mood changes
  • Serious adverse effects: Bone mineral density loss (dose- and duration-dependent), suicidal ideation/behavior (rare, monitor), hepatic transaminase elevations, hypoestrogenic effects
  • Drug interactions: Strong OATP1B1 inhibitors contraindicated (increase elagolix exposure 4-5x); P-gp inducers may reduce efficacy; CYP3A substrates with narrow therapeutic index (digoxin) — monitor
  • Pregnancy/nursing: Contraindicated; non-hormonal contraception required during treatment (hormonal contraceptives may have reduced efficacy)
  • Special populations: Dose-dependent BMD loss is the primary safety concern — lower dose (150 mg QD) causes minimal loss; higher doses require monitoring. Not recommended in women with osteoporosis or additional risk factors for bone loss. Mild hepatic impairment: use lower dose; moderate: limit higher dose to 6 months.

Synergistic Combinations

  • Relugolix — Same pharmacological class (oral GnRH antagonist); relugolix targets prostate cancer while elagolix targets women's health conditions
  • Leuprolide — Injectable GnRH agonist that elagolix may replace for endometriosis, offering oral convenience and dose-titratable suppression
  • Goserelin — Another injectable GnRH agonist alternative for endometriosis

Related Research

PMID Title Year Study Type
28525302 Treatment of endometriosis-associated pain with elagolix (Elaris EM-I/II) 2017 RCT
31971678 Elagolix for heavy menstrual bleeding in women with uterine fibroids (Elaris UF-I/II) 2020 RCT

References

Related

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