Gonadorelin

Gonadorelin is a synthetic peptide and a peptide hormone, specifically acting as a decapeptide (a chain of 10 amino acids) that mirrors naturally occurring gonadotropin-releasing hormone (GnRH). It stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Key Benefits

May support natural luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production
Commonly researched for supporting testosterone production and reproductive hormone balance
May help support fertility and healthy reproductive function
Research suggests potential benefits for hormonal regulation and endocrine system support

Order Now

FDA-Approved Uses

⚠️ COMPLEX REGULATORY STATUS ⚠️

Gonadorelin IS FDA-approved but NO commercially manufactured FDA-approved human product is currently available in the USA. Both original commercial brands (Factrel and Lutrepulse) have been discontinued. Gonadorelin is listed on the FDA 503A Bulks List as Category 1 — meaning it CAN be legally compounded by licensed 503A compounding pharmacies with a valid physician prescription.

Original FDA-approved indications:

1. Diagnostic Testing of Hypothalamic-Pituitary-Gonadotropic Function (Factrel)

Single-dose test to evaluate whether the pituitary gland can respond to GnRH by releasing LH and FSH. Used to diagnose hypogonadism, delayed puberty, hypothalamic amenorrhea, and pituitary dysfunction.
[Factrel commercially discontinued for human use; current Factrel product is VETERINARY (cattle only) — do not confuse]

2. Induction of Ovulation in Anovulatory Women with Hypothalamic Amenorrhea (Lutrepulse):

Pulsatile IV administration via pump to restore natural GnRH pulsatility and induce ovulation in women with primary hypothalamic amenorrhea (absence of GnRH pulses, not pituitary failure).
[Lutrepulse commercially discontinued]

Current off-label uses (most common clinical use via compounding):
3. Testosterone Replacement Therapy (TRT) adjunct:
To preserve testicular function, prevent testicular atrophy, and maintain fertility in men on TRT (testosterone suppresses natural LH/FSH → testicular atrophy; gonadorelin counters this).
4. Male fertility support: Stimulate endogenous testosterone and sperm production in hypogonadal men who wish to preserve fertility.
5. Hypogonadism diagnostics: Stimulation test for LH/FSH response assessment.

Trade Names in USA and Manufacturers

No currently available FDA-approved commercial human product in the USA.

Historical brands (both discontinued for human use):

Factrel (gonadorelin hydrochloride) — originally Wyeth-Ayerst; later Pfizer
DISCONTINUED for human use. Current Factrel product is VETERINARY (cattle IM injection) — NOT for human use.
Lutrepulse (gonadorelin acetate) — Ortho-McNeil Pharmaceutical; DISCONTINUED
Was used with a special pulsatile IV pump for ovulation induction

Current US availability:

Licensed 503A compounding pharmacies: LEGAL with valid physician prescription (Category 1 status)
Available as: Lyophilized powder for reconstitution (SC injection)
Most common compounded form: 100 mcg/mL solution
Grey-market research peptide vendors: Available but not pharmaceutical-grade

Molecular identity:

Synthetic decapeptide (10 amino acids): identical to endogenous GnRH
Sequence: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂
MW: 1,182.33 Daltons (free base)
Also available as hydrochloride salt (Factrel) and acetate salt (Lutrepulse)
Half-life: Distribution 2–10 minutes; Terminal 10–40 minutes (very short)
Metabolized by hydrolysis into smaller peptide components

Dosage

DIAGNOSTIC TEST (original Factrel indication — still performed):

Dose: 100 mcg SC or IV single injection
Timing: Blood samples taken at 0, 15, 30, 45, 60, and 120 minutes post-injection
Measure: LH and FSH response
Normal: ≥3-fold rise in LH

OVULATION INDUCTION (original Lutrepulse protocol — pulsatile pump):

Dose: 5 mcg per pulse IV
Frequency: 1 pulse every 90 minutes via portable IV pump
Duration: Until ovulation confirmed; monitor with ultrasound and LH levels
[Requires hospital or specialist fertility clinic setting]

TRT ADJUNCT — Testicular preservation (most common current compounded use):

Dose: 100 mcg SC per injection
Frequency: 2–3 times per week (e.g., Mon/Wed/Fri)
Route: Subcutaneous injection, abdomen
Duration: Throughout TRT course
Goal: Maintain testicular volume, LH response, and fertility potential during exogenous testosterone use

Male Fertility / Hypogonadism:
100–250 mcg SC 2–3x/week (individualized per physician)
Monitor: LH, FSH, testosterone, sperm count

Reconstitution (compounded):
Lyophilized powder; reconstitute with Bacteriostatic Water
Store lyophilized below 25°C; reconstituted solution refrigerate and use within 14–21 days

Pricing

No commercially available pricing (no US brand product).

Compounded gonadorelin (503A pharmacy, legal with prescription):
100 mcg/mL solution (typically 10 mL multi-dose vial):
~$50–$150/month depending on pharmacy and dose
[This is one of the more affordable compounded peptides given its small dosing]

Telemedicine TRT clinics (gonadorelin as TRT add-on):
~$30–$80/month added to TRT subscription cost

Research peptide vendors (unregulated):
~$20–$50 per vial

Tips

Gonadorelin is Category 1 — it CAN be legally prescribed and compounded by licensed 503A pharmacies. Unlike most peptides in this document, you can obtain pharmaceutical-grade compounded gonadorelin legally with a prescription.
Do NOT confuse compounded human gonadorelin with the current veterinary Factrel product (cattle IM injection).
For men on TRT: Gonadorelin is the preferred option over hCG for maintaining testicular function in many protocols, as it preserves the full LH/FSH response rather than just mimicking LH.
The very short plasma half-life (10–40 minutes terminal) means frequent dosing (2–3x/week) is required to maintain meaningful effect — unlike GnRH analogues (leuprolide, histrelin) which have longer half-lives.
For fertility and ovulation induction: The pulsatile pump method (Lutrepulse protocol) achieves more physiological GnRH pulsatility than SC bolus dosing — discuss with a reproductive endocrinologist.
Monitor LH, FSH, testosterone, and (for fertility use) sperm counts regularly during treatment.

Side Effects

From original Factrel and Lutrepulse FDA prescribing information and clinical trial data:

Common:
– Injection site reactions: Pain, redness, swelling, bruising at SC injection site
– Flushing / warmth sensation shortly after injection
– Headache
– Nausea (mild)
– Dizziness or lightheadedness

Fertility-specific (ovulation induction use — serious):
– Ovarian Hyperstimulation Syndrome (OHSS): Can be severe; symptoms include severe abdominal pain, bloating, nausea, vomiting, diarrhea, significant weight gain, shortness of breath, decreased urine output. Requires immediate medical attention.
– Multiple gestation (twins, triplets): Risk when used for ovulation induction
– Ovarian cysts or enlargement
– Possible association with ovarian cancer (rare; causality not established)

Hormone-related:
– Elevated LH/FSH → increased sex hormone levels: May stimulate growth of hormone-dependent tumors (e.g., prostate cancer, estrogen-sensitive breast cancer)
– In men on TRT: May cause fluctuation in testosterone levels

Rare:
– Anaphylaxis / hypersensitivity: Rare but reported
– Pituitary apoplexy (rare): Reported with GnRH agonist class in patients with pituitary adenoma

Contraindications

Per original Factrel and Lutrepulse FDA prescribing information:

Contraindicated:
– Known hypersensitivity to gonadorelin or any component
– GnRH-secreting pituitary adenoma (gonadotropin-releasing hormone adenoma): Use may cause problems in pituitary gland and sudden blindness — rare condition but absolute contraindication
– Hormone-dependent tumors: Any condition worsened by increased estrogens, progestins, or androgens (e.g., estrogen-sensitive breast cancer, prostate cancer) — LH/FSH stimulation increases gonadal steroid production
– Pregnancy (for non-diagnostic use): Gonadorelin can stimulate uterine contractions; not appropriate during established pregnancy

Use with caution:
– Concurrent use of medications affecting pituitary gonadotropin secretion (androgens, estrogens, progestins, glucocorticoids, dopamine agonists): May blunt or alter LH/FSH response
– Digoxin and oral anticoagulants: Possible interaction with gonadorelin (noted in original Factrel label)
– Athletes subject to WADA testing: Prohibited S2 — do not use
– Patients with pituitary dysfunction: Response to test dose may be subnormal (expected finding, not a contraindication to diagnostic use)

Pharmacology

Gonadorelin is a synthetic decapeptide (10 amino acids) with a chemical composition and structure IDENTICAL to endogenous gonadotropin-releasing hormone (GnRH), which is produced in the hypothalamus and released in a pulsatile manner. Sequence: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂ (pyroglutamic acid at position 1; C-terminal amide). MW: 1,182.33 Daltons (free base). Available as hydrochloride (Factrel) and acetate (Lutrepulse) salts. Pharmacokinetics: Very short plasma half-life — distribution half-life 2–10 minutes, terminal half-life 10–40 minutes. Metabolized by peptide hydrolysis. Cleared renally and hepatically. This extremely short half-life is clinically significant: a bolus SC injection produces a brief LH/FSH pulse, while a continuous IV infusion paradoxically DOWN-regulates pituitary GnRH receptors and suppresses gonadotropin secretion (the basis of GnRH agonist therapy for prostate cancer and endometriosis — the opposite effect from pulsatile dosing).

Mechanism of action

Gonadorelin binds to GnRH receptors (GnRHR) on gonadotroph cells of the anterior pituitary gland:

PULSATILE administration (natural pattern / therapeutic use):
GnRH receptor activation → activates Gq/11 protein → phospholipase C activation → IP3/DAG increase → intracellular calcium release → stimulates synthesis and release of LH (luteinizing hormone) and FSH (follicle-stimulating hormone) from pituitary gonadotrophs.

Downstream hormonal cascade:
LH → stimulates Leydig cells (testes) → testosterone production
FSH → stimulates Sertoli cells (testes) → sperm production; stimulates ovarian follicle development

CONTINUOUS administration paradox:
Continuous (non-pulsatile) GnRH stimulation → receptor downregulation and desensitization → SUPPRESSION of LH and FSH → decreased gonadal steroid production. This is the mechanism exploited by long-acting GnRH agonists (leuprolide, goserelin) in prostate cancer and endometriosis treatment.

Clinical implication for compounded gonadorelin:
Short-acting bolus SC injections 2–3x/week → pulsatile stimulation → maintains/increases LH, FSH, testosterone, and sperm production. This is the desired effect for TRT adjunct and fertility support.

Result Claims By Different Companies

Wyeth-Ayerst / Pfizer (original Factrel — diagnostic use):
– Demonstrated reliable LH/FSH stimulation response in healthy adults and ability to distinguish pituitary from hypothalamic causes of hypogonadism
– LH rose to ≥3x baseline in healthy adults within 30 minutes post-injection
– Subnormal responses documented in 100% of panhypopituitary patients and 95% of prepubertal panhypopituitary patients — confirming diagnostic utility

Ortho-McNeil (original Lutrepulse — ovulation induction):
– Pulsatile IV gonadorelin (5 mcg every 90 min) successfully induced ovulation in women with hypothalamic amenorrhea
– Pregnancy rates comparable to other ovulation induction methods in appropriately selected patients (hypothalamic amenorrhea)
– More physiological than exogenous gonadotropins (FSH/LH injections) — restores natural pulsatile feedback rather than bypassing the pituitary

Current compounded clinical use (TRT adjunct — off-label, observational data):
– Preserved testicular volume and maintained LH/FSH response in men on TRT when compared to TRT without gonadal support
– Maintained sperm production in men on TRT who wished to preserve fertility
– Preferred over hCG in some protocols as it stimulates both LH and FSH vs. hCG (LH-only mimic)

⚠️ No Phase 3 RCTs for current off-label compounded uses (TRT adjunct, male fertility). Efficacy in these settings is supported by pharmacological rationale and observational clinical data, not controlled trials.

Disclaimer

This content about “Gonadorelin” is for informational and educational purposes only, is not medical advice, does not replace consultation with a licensed healthcare professional, and affiliate links may result in compensation at no additional cost to you.