Cetrorelix

What is Cetrorelix?

Cetrorelix (brand name CETROTIDE, development code SB-75) is a synthetic decapeptide GnRH receptor antagonist approved by the FDA on August 11, 2000 for inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation for in vitro fertilization (IVF). It was the first GnRH antagonist approved for use in assisted reproductive technology and remains a standard component of modern IVF protocols.

Cetrorelix is a self-administered subcutaneous injection used during a 5-12 day window of ovarian stimulation, typically once daily at a 0.25 mg dose or as a single 3 mg dose.

Structure and Mechanism

Cetrorelix is engineered with multiple D-amino-acid substitutions at positions 1, 2, 3, 6, and 10 of the native GnRH sequence, producing a peptide that binds the GnRH receptor with high affinity but does not activate it — unlike GnRH agonists which produce paradoxical receptor activation followed by desensitization.

The pharmacological consequence is immediate and reversible suppression of pituitary LH and FSH secretion:

• No initial gonadotropin "flare" (avoiding the early-cycle problems of agonist protocols)
• Rapid onset — LH suppression within hours
• Rapid offset — pituitary function recovers within days of discontinuation

This pharmacology is critical for IVF: during ovarian stimulation, multiple follicles are recruited with exogenous FSH, but rising estradiol can trigger a premature endogenous LH surge that initiates ovulation before egg retrieval. Cetrorelix prevents this surge while leaving exogenous gonadotropin signaling intact.

Clinical Evidence

The Cochrane systematic review of GnRH antagonists vs the GnRH agonist long protocol in IVF (Al-Inany et al., 2016, 73 trials, 12,212 women) showed:

• Equivalent live birth rates
• Significantly lower risk of ovarian hyperstimulation syndrome (OHSS) with antagonist protocols (RR 0.61)
• Shorter stimulation duration
• Lower total gonadotropin dose required

Approval History

• August 11, 2000 — FDA approval (Cetrotide)
• April 1999 — EMA approval (predates FDA)
• 2018-2024 — Multiple generic cetrorelix acetate approvals

Place in Therapy

Cetrorelix is one of two GnRH antagonists used in IVF (with ganirelix). The two are largely interchangeable. GnRH antagonist protocols are now the most commonly used IVF protocol globally, having displaced GnRH agonist long protocols in many programs because of:

• Reduced OHSS risk
• Shorter overall cycle duration
• More flexible scheduling
• Equivalent pregnancy outcomes

Cetrorelix has also been studied for benign prostatic hyperplasia, uterine fibroids, and prostate cancer, but is not approved for these indications.

Safety Profile

The most common adverse events are:

• Mild local injection-site reactions
• Headache, nausea
• Ovarian hyperstimulation syndrome (lower risk than agonist protocols, but still possible due to gonadotropin stimulation)

There are no class-effect bone or systemic concerns because cetrorelix is used only briefly during the IVF cycle.

Distinction from Ganirelix and Degarelix

Three GnRH antagonists:

Cetrorelix and ganirelix are clinically interchangeable for IVF; degarelix is structurally distinct and used as a monthly depot for prostate cancer.