Ageless Pep Academy Clinical Education · Licensed Prescribers

Relugolix

Relugolix

⚠️ Structural Separation Notice

The Ageless Pep Academy is a clinical education property independent from any commerce operation. Any references in this profile to Ageless Peps product SKUs, pricing, or the agelesspeps.com domain are for completeness and transparency; they are not endorsements and do not form part of the clinical education content. Clinicians are responsible for independent verification of any product sourcing decision. The Academy's Medical Director provides editorial oversight only and does not endorse commercial products.

Non-peptide oral GnRH receptor antagonist; FDA-approved for advanced prostate cancer (Orgovyx). Included in this vault for educational completeness alongside peptide-based GnRH modulators.

Quick Facts

Property Value
Also Known As Orgovyx, TAK-385, Relumina (Japan)
Category GnRH Antagonist (Non-peptide) / Sexual Health
Sequence N/A — Relugolix is a non-peptide small molecule, not a peptide. It is a thieno[2,3-b]pyridine derivative that acts on the same GnRH receptor targeted by peptide GnRH agonists and antagonists.
Molecular Weight ~623.5 Da
Molecular Formula C29H27F2N7O5S
PubChem CID 11656903
Administration Oral tablet
Typical Dose Range 120 mg once daily (after 360 mg loading dose on day 1)
Half-Life ~25 hours (terminal half-life ~60 hours)
Storage Room temperature (20-25C); no special storage requirements
FDA Status Approved (2020) — Orgovyx for advanced prostate cancer. Also approved in combination with estradiol/norethindrone acetate as Myfembree (2021) for uterine fibroids and endometriosis.
WADA Status Not prohibited (FDA-approved medication)

Important Note: Relugolix 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

Relugolix is an orally bioavailable, non-peptide GnRH receptor antagonist that competitively blocks the GnRH receptor on anterior pituitary gonadotroph cells. Unlike peptide GnRH antagonists such as degarelix, relugolix achieves oral bioavailability through its small molecule structure, bypassing the need for injectable administration.

Upon oral absorption, relugolix rapidly binds to and blocks pituitary GnRH receptors, preventing endogenous GnRH from stimulating LH and FSH release. This produces dose-dependent suppression of gonadotropins and downstream sex steroids (testosterone in males, estradiol in females). Castrate testosterone levels are achieved in 56% of patients by day 4 after the loading dose — faster than leuprolide but slightly slower than injectable degarelix (PMID: 32469183).

A critical pharmacological advantage is the absence of testosterone flare: as a direct receptor antagonist, relugolix never activates the GnRH receptor and therefore does not produce the transient gonadotropin/testosterone surge seen with GnRH agonists. Additionally, because it is a small molecule with a relatively short half-life, testosterone recovery after discontinuation is substantially faster than with depot GnRH agonists (median 86 days vs 112 days for leuprolide) (PMID: 38143206).

Key Research Areas

  1. HERO trial — oral ADT for prostate cancer — Phase III trial demonstrated relugolix superiority over leuprolide for sustained castration (96.7% vs 88.8% at 48 weeks), with 46% reduction in major adverse cardiovascular events (PMID: 32469183)
  2. Cardiovascular safety advantage — MACE rate 2.9% relugolix vs 6.2% leuprolide (HR 0.46), suggesting GnRH antagonism may be cardiovascularly safer than agonism (PMID: 32469183)
  3. Testosterone recovery — Significantly faster and more complete testosterone recovery after discontinuation (54% recovered to >280 ng/dL at 90 days vs 3.2% with leuprolide), enabling better intermittent ADT strategies (PMID: 38143206)
  4. Comprehensive clinical review — Review article synthesizing pharmacology, efficacy, and safety data (PMID: 36652173)
  5. Endometriosis (as Myfembree combination) — Approved in Japan and US (as combination product) for endometriosis and uterine fibroids pain management

Evidence Level Summary

Evidence Type Count Notes
Systematic reviews 0 —
Human RCTs 2 HERO Phase III trial; testosterone recovery analysis
Human observational 0 —
Narrative reviews 1 Comprehensive review in Targeted Oncology
In vitro 0 —

Clinical Applications

  • Cancer Adjunct Therapy — First-line oral androgen deprivation therapy for advanced prostate cancer; preferred when cardiovascular risk is a concern
  • Sexual Health — Testosterone suppression with the convenience of oral dosing and rapid reversibility
  • Endometriosis — As Myfembree combination (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg) for endometriosis-associated pain
  • Uterine Fibroids — As Myfembree combination for heavy menstrual bleeding associated with uterine fibroids

Protocols Using This Peptide

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

Ageless Peps Products

  • Not sold by Ageless Peps. Relugolix is an FDA-approved prescription medication (Orgovyx/Myfembree) available only through licensed pharmacies.

Dosing Reference

FDA-Approved Dosing

Indication Dose Route Frequency Duration Source
Advanced prostate cancer (loading) 360 mg Oral Once on day 1 Day 1 only FDA label (Orgovyx)
Advanced prostate cancer (maintenance) 120 mg Oral Once daily Ongoing FDA label (Orgovyx)
Endometriosis / Uterine fibroids 40 mg (+ estradiol/NETA) Oral Once daily Up to 24 months FDA label (Myfembree)

Cycling

Not applicable in the traditional peptide cycling sense. Used continuously for prostate cancer. For endometriosis/fibroids (Myfembree), treatment is limited to 24 months due to bone mineral density concerns. The rapid testosterone recovery profile makes relugolix particularly well-suited for intermittent ADT protocols where planned treatment breaks are employed.

Contraindications & Safety

  • Contraindications: Pregnancy (expected to cause fetal harm based on mechanism); known hypersensitivity
  • Common side effects: Hot flashes (54%), musculoskeletal pain (30%), fatigue (26%), diarrhea (12%), constipation (12%)
  • Serious adverse effects: QTc prolongation, major adverse cardiovascular events (2.9% in HERO trial), bone mineral density loss with prolonged use, hepatic injury (rare)
  • Drug interactions: Strong P-gp inhibitors and combined P-gp/CYP3A inducers should be avoided (affects oral bioavailability); caution with QTc-prolonging drugs
  • Pregnancy/nursing: Contraindicated; verify pregnancy status before initiation
  • Special populations: No dose adjustment for mild-to-moderate renal or hepatic impairment; daily oral dosing requires patient adherence (unlike depot injections); take without regard to food

Synergistic Combinations

  • Degarelix — Both are GnRH antagonists; degarelix provides guaranteed monthly depot compliance while relugolix offers oral convenience
  • Elagolix — Same pharmacological class (oral GnRH antagonist); elagolix indicated for endometriosis/fibroids while relugolix (as Orgovyx) targets prostate cancer
  • Leuprolide — GnRH agonist that relugolix may replace, particularly in CV-high-risk patients

Related Research

PMID Title Year Study Type
32469183 Oral relugolix for ADT in advanced prostate cancer (HERO trial) 2020 RCT
36652173 Relugolix: a review in advanced prostate cancer 2023 Narrative Review
38143206 Testosterone recovery for relugolix vs leuprolide: HERO results 2024 RCT

References

Related

#peptide #sexual-health #reproductive #fda-approved #not-sold #oral