Prostate cancer cells require androgens (testosterone) in order to grow. Removing androgens is an effective way of temporarily reducing the tumour bulk and delaying growth.
Androgens can be testicular or adrenal in origin. The secretion of testosterone is stimulated by the direct action of luteinising hormone (LH) on receptors located on specialised cells (Leydig cells) found in the testes. LH is stimulated by luteinising hormone-releasing hormone (LHRH) produced by the pituitary.
The adrenals secrete precursors, which are converted into androgens in the peripheral tissues and in the prostate itself.
Testosterone levels may be reduced surgically or medically. The surgical approach is castration with bilateral orchidectomy. The medical approach uses drugs; LHRH analogues, and anti-androgens.
LHRH analogues (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 causes a temporary increase in testosterone lasting between 5 and 12 days. And this is thought to account for the worsening of symptoms experienced by some men at this time (‘tumour flare’). It can be reduced by giving 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:
- bicalutamide (Casodex)
- flutamide (Drogenil®)
- cyproterone acetate (Cyprostat®).