Gonadorelin

Gonadorelin is synthetic gonadotropin-releasing hormone (GnRH), identical to the endogenous decapeptide produced by the hypothalamus. When administered in a pulsatile fashion (mimicking natural hypothalamic output), it stimulates LH and FSH release from the anterior pituitary, maintaining downstream gonadal function — including spermatogenesis and intratesticular testosterone production. This makes gonadorelin the emerging replacement for HCG in TRT fertility preservation protocols, driven by the 2020 FDA enforcement action that restricted compounding pharmacies from producing HCG (as a biologic under BPCIA). Unlike continuous GnRH agonist administration (which causes receptor downregulation and paradoxical LH suppression — the basis of leuprolide/ goserelin in prostate cancer), pulsatile gonadorelin at physiological frequencies (every 90-120 minutes or simplified to 2x/day subcutaneous) maintains gonadotropin secretion. FDA-approved for diagnostic GnRH stimulation testing and therapeutic use in hypothalamic amenorrhea (Lutrepulse). Now widely prescribed off-label by TRT clinics as an HCG alternative.