Cetrorelix

Mechanism

Cetrorelix is a synthetic decapeptide that acts as a competitive antagonist at the gonadotropin-releasing hormone (GnRH) receptor in the anterior pituitary. Unlike GnRH agonists, which initially stimulate gonadotropin release before causing downregulation, cetrorelix binds to and blocks GnRH receptors immediately, preventing endogenous GnRH from activating them. This produces a rapid, dose-dependent suppression of LH and FSH secretion within hours, without a stimulatory 'flare' phase. Pituitary function recovers within 24–48 hours of the last dose for the 0.25 mg formulation, or within approximately 96 hours for the 3 mg formulation. The competitive mechanism means that suppression is reversible and dose-dependent.

Evidence base

Controlled Ovarian Stimulation (ART)

Multiple randomised controlled trials have demonstrated that cetrorelix-based antagonist protocols achieve comparable oocyte retrieval, fertilisation, and clinical pregnancy rates to long GnRH agonist protocols, while significantly reducing the incidence of ovarian hyperstimulation syndrome (OHSS) — a potentially life-threatening complication of ovarian stimulation (Al-Inany et al., Cochrane, 2016).

Oncology Applications

GnRH receptors are expressed on many hormone-dependent tumours. Cetrorelix has shown antiproliferative effects in preclinical models of ovarian, endometrial, and breast cancer. A Phase II trial in recurrent ovarian cancer showed disease stabilisation in some patients (Verschraegen et al., Am J Obstet Gynecol, 2003). These applications remain investigational.

Benign Gynaecological Conditions

Small studies have explored cetrorelix for uterine fibroids and endometriosis, with reductions in fibroid volume and symptom improvement, but evidence is limited and it is not licensed for these indications.

Protocols

Single-Dose Protocol (Licensed)

• 3 mg subcutaneous injection administered on stimulation day 7.
• If ovarian stimulation continues beyond 96 hours after the 3 mg dose, 0.25 mg daily doses are added starting on the fifth day after the 3 mg injection.

Multiple-Dose Protocol (Licensed)

• 0.25 mg subcutaneous injection daily.
• Initiate on stimulation day 5 or 6, or when a follicle reaches ≥14 mm on ultrasound.
• Continue daily through the day of hCG trigger administration.
• Administer at approximately the same time each day (morning or evening).

All protocols are performed under specialist medical supervision in a licensed fertility clinic. This information is for educational purposes only.

UK legal status

Cetrorelix is a prescription-only medicine (POM) in the UK under the Human Medicines Regulations 2012. It is licensed for the prevention of premature ovulation in women undergoing controlled ovarian stimulation for ART. Supply without a valid prescription is unlawful. It is not classified as a controlled substance under the Misuse of Drugs Act 1971.

The MHRA regulates cetrorelix-containing products through the standard medicines licensing framework. The licensed product (Cetrotide) has a UK marketing authorisation.

Vendor notes

As a licensed POM, cetrorelix is dispensed by registered pharmacies upon presentation of a valid NHS or private prescription, typically in the context of a licensed fertility clinic. It is not available from research peptide vendors.