COMMON INITIAL DOSING REGIMENS

• A typical starting dose is 100 mcg (subcutaneously) or 500mcg (oral troche) 1–3 times weekly. 

MECHANISM OF ACTION

• Gonadorelin is a synthetic analog of gonadotropin-releasing hormone (GnRH). It stimulates the pituitary gland to release LH and FSH, which in turn promote testosterone production in the testes. Unlike GnRH agonists, gonadorelin is administered intermittently, mimicking the natural pulsatile release of GnRH and avoiding downregulation of pituitary receptors.

• Gonadorelin prevents testicular shrinkage primarily by stimulating the hypothalamic-pituitary-gonadal (HPG) axis, maintaining the physiological function of the testes during periods of testosterone replacement therapy (TRT) or other conditions that suppress natural gonadotropin production. 

COMMON SIDE EFFECTS

• General: Flushing, dizziness, and mild nausea immediately following administration.

• Endocrine: Overstimulation of LH and FSH can transiently elevate estradiol levels, potentially causing mild gynecomastia or water retention.

• Injection Site: Local irritation, redness, or swelling.

• Rare: Headache or abdominal discomfort.

CONTRAINDICATIONS

• Absolute: Known hypersensitivity to gonadorelin or its excipients.

• Relative: Use with caution in patients with pituitary tumors or conditions impairing normal pituitary function. It may be ineffective in primary hypogonadism due to testicular failure.

COMPARISON WITH OTHER AGENTS

• Human Chorionic Gonadotropin (hCG): Like gonadorelin, hCG can also prevent testicular shrinkage, but it acts directly as an LH analog. Gonadorelin, however, stimulates the entire HPG axis, which can lead to a more natural hormonal balance.

• Clomiphene Citrate or Enclomiphene: These selective estrogen receptor modulators (SERMs) also stimulate the HPG axis but do so by blocking estrogen’s negative feedback on the hypothalamus. Gonadorelin is often preferred in cases where a more direct and precise mechanism is required.

MORE INFORMATION

• Boeri L. Gonadotropin Treatment for the Male Hypogonadotropic Hypogonadism. Curr Pharm Des. 2021 [PubMed Link]

• Corona G. The pharmacotherapy of male hypogonadism besides androgens. Expert Opin Pharmacother. 2015 [PubMed Link]

• Zitzmann M. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000 [PubMed Link]