Gonadorelin: Synthetic GnRH, Uses and PH Status

Abstract still life: a small brass metronome casting a sharp shadow on linen — **Gonadorelin.** Illustration, not a product photo.

Research compound. Not approved by FDA Philippines for human use unless stated. Nothing here is a dosing recommendation or medical advice.

What it is

Gonadorelin is a synthetic copy of gonadotropin-releasing hormone (GnRH), the ten amino acid peptide the hypothalamus uses to switch on the reproductive axis. The sequence is the same as the natural hormone; the drug name simply refers to the manufactured version, sold as a hydrochloride or acetate salt.

It has a real regulatory history. In the US, Factrel was approved in 1982 as a diagnostic agent for testing the pituitary, and Lutrepulse was approved in 1989, with orphan designation, for inducing ovulation with a pulsatile pump. Drugs@FDA now lists both as discontinued. Gonadorelin products are also used in veterinary medicine.

How it works

GnRH binds receptors on the gonadotrope cells of the anterior pituitary, which respond by releasing luteinising hormone (LH) and follicle-stimulating hormone (FSH). LH drives testosterone production in the testes and triggers ovulation; FSH supports sperm production and follicle growth.

The critical detail is timing. The hypothalamus releases GnRH in pulses, and the pituitary responds properly only to pulses. That is why Lutrepulse was delivered by a pump giving a small dose every 90 minutes rather than a daily injection. Constant stimulation has the opposite effect: long-acting GnRH agonists such as leuprorelin and goserelin are used clinically to suppress the axis.

Gonadorelin is also extremely short-lived. The Lutrepulse monograph gives an initial plasma half-life of 2 to 10 minutes and a terminal half-life of 10 to 40 minutes. A single injection produces a brief LH and FSH pulse, not a sustained signal.

Because it acts on the pituitary, gonadorelin only works if the pituitary is intact. Compare hCG, which bypasses the pituitary, and kisspeptin, which acts one step higher, on the GnRH neurons themselves.

What the research found

Diagnostic use (Factrel)

Factrel was indicated for evaluating the functional capacity and response of the pituitary gonadotropes, including checking residual pituitary function after removal of a pituitary tumour. The label describes a 100 mcg dose given subcutaneously or intravenously, with blood drawn before the injection and at intervals up to two hours afterwards to measure the LH response.

Ovulation induction (Lutrepulse)

The Lutrepulse monograph describes use in women with primary hypothalamic amenorrhea, where the hypothalamus fails to produce GnRH but the pituitary and ovaries are normal. In the studies summarised there, 45 of 48 patients ovulated and 25 of 43 became pregnant. At the standard regimen of 5 mcg every 90 minutes, 68% of treatment cycles produced ovulation. Twelve percent of the resulting pregnancies were multiple.

Use in men

Gonadorelin is discussed in men's health circles as a way to keep the testes active during testosterone therapy. We did not find a labelled indication or a controlled trial supporting that use in the sources we reviewed, and the need for pulsatile delivery is a practical problem for any once or twice daily injection schedule. Decisions about it belong with a physician.

Side effects reported in studies and labels

The Factrel label lists headache, flushing, nausea, abdominal discomfort, dizziness, lightheadedness and injection-site reactions, with rare hypersensitivity reactions including anaphylaxis. The Lutrepulse monograph reports superficial thrombophlebitis and injection-site irritation from the pump line, one case of moderate ovarian hyperstimulation among 268 patients, and the multiple pregnancy rate noted above.

Gonadorelin vs hCG vs kisspeptin

	Acts on	Needs working pituitary	Status
Gonadorelin	Pituitary GnRH receptor	Yes	US human products discontinued
hCG	LH receptor in testes and ovaries	No	Approved, marketed
Kisspeptin	GnRH neurons in the hypothalamus	Yes, and a working hypothalamus	Investigational

Status in the Philippines

We could not confirm a gonadorelin product registered for human use with FDA Philippines. Longer-acting GnRH agonists used in cancer and fertility care are a separate class of medicine. Gonadorelin sold online as a research peptide is not a registered medicine. For male athletes, the WADA Prohibited List bans GnRH (gonadorelin) and its agonist analogues under section S2.

Storage

The Factrel label called for room temperature storage and use within one day of reconstitution. Research vials are best kept refrigerated before mixing, and at 2 to 8°C afterwards, particularly through Philippine heat and brownouts. The reconstitution calculator handles the arithmetic.

Doses used in published research

What investigators actually administered, as reported in the cited study. This is a record of the literature, not a recommendation.

Study	Population	Regimen
Factrel US label	Patients undergoing testing of pituitary gonadotrope function	100 mcg subcutaneous or intravenous, single dose, with LH sampled over 2 hours
Lutrepulse product monograph	Women with primary hypothalamic amenorrhea	5 mcg every 90 minutes by pulsatile pump, subcutaneous or intravenous (studied range 1 to 20 mcg per pulse)

Common questions

Is gonadorelin still approved?

In the US, both human products have been discontinued: Factrel, approved in 1982 as a diagnostic, and Lutrepulse, approved in 1989 for pulsatile ovulation induction. Drugs@FDA lists both as discontinued.

What is the difference between gonadorelin and hCG?

Gonadorelin is a copy of GnRH, the hypothalamic signal that tells the pituitary to release LH and FSH. hCG mimics LH itself and acts directly on the testes or ovaries, so it works even when the pituitary does not.

Why does gonadorelin have to be given in pulses?

Natural GnRH is released in bursts. The approved ovulation-induction product used a pump that delivered a small dose every 90 minutes to copy that rhythm. Long-acting GnRH agonists, which give a constant signal, are used in medicine for the opposite purpose of shutting the axis down.

Is gonadorelin banned in sport?

Yes, for men. The WADA Prohibited List names gonadotrophin-releasing hormone (GnRH, gonadorelin) and its agonist analogues under S2 as testosterone-stimulating peptides prohibited in males.