Gonadorelin

What it is

Gonadorelin is a synthetic decapeptide, a chain of ten amino acids, that is identical to endogenous gonadotropin-releasing hormone (GnRH). GnRH is the hypothalamic hormone that prompts the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The PeptidesAI encyclopedia describes gonadorelin as having a half-life measured in minutes.

The FDA's Drugs@FDA database lists two gonadorelin products, Factrel (gonadorelin hydrochloride, approved in 1982) and Lutrepulse (gonadorelin acetate, approved in 1989), and marks both as discontinued. The encyclopedia describes the historical approval as being for diagnostic use. Compounded gonadorelin sold today is not an FDA-approved product.

How it's thought to work

Gonadorelin binds GnRH receptors on the pituitary to trigger LH and FSH release, which drives downstream production of gonadal hormones. Timing matters. In rhesus monkeys with hypothalamic lesions, constant GnRH infusion failed to restore sustained gonadotropin secretion, whereas intermittent administration at the physiological hourly frequency did restore it, and starting continuous administration could cause desensitization or down-regulation. That pattern is the principle behind GnRH agonist therapies.

What the research says

In a nonrandomized study of 28 men with azoospermia due to congenital hypogonadotropic hypogonadism (a condition with deficient GnRH signaling), a pulsatile gonadorelin pump (10 men) was compared with cyclical gonadotropin therapy (18 men). Spermatogenesis occurred earlier with the pump (median 6 versus 14 months), and occurred in 90% of men on the pump and 83.3% on gonadotropins, a difference that was not statistically significant.

Gonadorelin has long-established pharmacology. Its current compounded use, most often described as supporting natural testicular function, is off-label and not FDA-approved. The study above examined pulsatile pump delivery in a different patient group.

Reported side effects

The PeptidesAI encyclopedia lists injection site reactions, headache, flushing and occasional nausea. In the pump study above, skin allergic erythema was reported as a common side effect.

Reconstitution

Gonadorelin is supplied as a lyophilized (freeze-dried) powder and is typically reconstituted with bacteriostatic (BAC) water before use. It commonly comes in 2 mg and 10 mg vials. The amount of peptide in the vial is fixed; the water added only changes how concentrated the solution is.

Worked example. A 2 mg vial is 2,000 mcg. Reconstituted with 2 mL of BAC water, that works out to 2,000 mcg ÷ 2 mL = 1,000 mcg/mL. On a U-100 insulin syringe, where each unit is 0.01 mL, each unit holds 1,000 × 0.01 = 10 mcg. Use the peptide reconstitution calculator to work out the concentration and units for any vial size and water volume.

Important notes

Gonadorelin affects reproductive hormone signaling. The branded products, Factrel and Lutrepulse, are discontinued, and compounded use is off-label and not FDA-approved.

Sources

1. Drugs@FDA: NDA 018123, FACTREL (gonadorelin hydrochloride). U.S. Food and Drug Administration, 2026. Announcement
2. Drugs@FDA: NDA 019687, LUTREPULSE KIT (gonadorelin acetate). U.S. Food and Drug Administration, 2026. Announcement
3. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Belchetz PE et al. Science, 1978. Preclinical
4. The Pulsatile Gonadorelin Pump Induces Earlier Spermatogenesis Than Cyclical Gonadotropin Therapy in Congenital Hypogonadotropic Hypogonadism Men. Zhang L et al. Am J Mens Health, 2019. Human trial

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Frequently asked questions

These questions cover the same ground as the sections above, in a shorter format.

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