LHRH agonists (pituitary down-regulators)
Exposure to LHRH analogues causes the pituitary's LHRH receptors to become desensitised (down-regulated). The down-regulating effect is not immediate but follows an initial stimulation of LH secretion. This stimulation of LH secretion causes a temporary increase in testosterone lasting between 5 and 12 days. This is thought to account for the worsening of symptoms experienced by some men, known as ‘tumour flare’. This worsening of symptoms can be minimised by the administration of an anti-androgen for the first few weeks of treatment.
The four main LHRH agonists are:
- goserelin (Zoladex®)
- leuprorelin (Prostap®)
- triptorelin (De-capeptyl®)
- buserelin (Suprefact®)
Anti-androgens
Anti-androgens act by blocking the binding of testosterone to receptors on the surface of the prostate cancer cell. The main ones are:
- cyproterone acetate (Cyprostat®)
- flutamide (Drogenil®)
Bicalutamide (Casodex®) 150mg should not currently be used for patients with localised prostate cancer (defined as early disease).
This recommendation, from the Department of Health in 2003 (30), follows results from a study of bicalutamide in early prostate cancer which showed a trend for an increase in the number of deaths in patients receiving Casodex 150mg when compared with patients who received placebo.
The NICE guidelines (3) suggest that hormone therapy for early prostate cancer (in terms of medical castration) should be fully discussed with patients.
Surgery - orchidectomy
Surgery is less commonly used these days as medical hormone therapy has become available. It is as effective as LHRH agonists, and has the advantage that regular injections are not required, but , unlike LHRH agonists, the effect is irreversible.
Surgery involves a simple operation to remove both testicles (bi-lateral orchidectomy), or the parts of the testicles that produce testosterone (subcapsular orchidectomy). Surgery is done under a general, local or spinal anaesthetic. Testicular prostheses can be placed into the scrotum at the same time as the operation.