Discontinued Sexual & Reproductive Health

Gonadorelin

also known as: Factrel, Lutrepulse, GnRH, LHRH

The native GnRH decapeptide — the hypothalamic signal that drives LH/FSH release and downstream testosterone/estradiol production. Historically FDA-approved (Factrel, Lutrepulse), now widely used in TRT-adjacent fertility protocols as a testicular-preservation alternative to HCG.

The endogenous hypothalamic decapeptide gonadotropin-releasing hormone, which signals the anterior pituitary to release luteinizing hormone and follicle-stimulating hormone; synthetic gonadorelin was historically FDA-approved as the diagnostic agent Factrel and the pulsatile infusion therapy Lutrepulse, and is now most prominent in men's-health clinics as a testicular-preservation adjunct to testosterone therapy used in preference to HCG.

Mechanism of action

Binds the GnRH receptor on anterior pituitary gonadotrophs in a pulsatile fashion, triggering LH and (to a lesser extent) FSH release. LH then stimulates testicular Leydig-cell testosterone production in men and ovarian theca-cell androgen synthesis in women; FSH supports spermatogenesis and folliculogenesis. The pulsatile-versus-continuous pharmacology is central: brief peaks preserve receptor signaling while continuous exposure produces receptor internalization and desensitization (exploited therapeutically by GnRH agonists in prostate cancer).

Primary uses

Testicular function preservation during testosterone therapy (off-label, community/men's-health-clinic protocols)
Historical: diagnostic evaluation of HPG axis (Factrel, discontinued)
Historical: primary hypothalamic amenorrhea (Lutrepulse, discontinued)

Typical dosing

100–300 (diagnostic); 25–200 (community TRT adjunct) mcg pulsatile every 90 min (Lutrepulse); twice weekly SC (community TRT use) (subcutaneous, intravenous, or pulsatile infusion)

Community TRT protocols commonly use 25–200 mcg SC 2–3 times weekly as an HCG alternative. This is an off-label use based on community experience — not supported by randomized trial evidence, which is why formal TRT guidelines still reference HCG. Pharmacokinetics favor HCG for sustained LH-like effect; gonadorelin's 4-minute half-life is a practical limitation.

Regulatory status

Previously FDA-approved as Factrel (diagnostic evaluation of hypothalamic-pituitary-gonadal function) and Lutrepulse (pulsatile infusion for primary hypothalamic amenorrhea). Both brand formulations were discontinued from the US market for commercial reasons, not safety; the active ingredient remains available via compounding pharmacies and is widely used off-label in men's-health practice as a substitute for HCG.

References

[fda-pi] Factrel (gonadorelin hydrochloride) Prescribing Information (historical).
[fda-pi] Lutrepulse (gonadorelin acetate) Prescribing Information (historical).
[pubmed] Filicori M, et al. "Pulsatile gonadotropin-releasing hormone administration for ovulation induction in hypothalamic amenorrhea." Fertil Steril, 1994;62:1-7.

Related peptides

HCG

An FDA-approved fertility and hypogonadism medication commonly discussed in peptide and TRT communities for post-cycle recovery and testicular preservation during testosterone therapy.

Sermorelin

The N-terminal 29 amino acids of native GHRH — a former FDA-approved diagnostic and pediatric GH-deficiency therapy, now widely compounded for adult anti-aging protocols.

Tesamorelin

An FDA-approved GHRH analog for reducing excess visceral fat in HIV-associated lipodystrophy.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.