Hormonal manipulation in prostatic cancer

The aims of hormonal treatment are to reduce circulating testosterone or to chemically oppose it. Options include:

• luteinising hormone releasing hormone agonists - which stimulate the release of LH from the anterior pituitary. Testicular testosterone synthesis is increased initially but is rapidly exhausted so circulating levels of testosterone are lowered. The treatment is effective but expensive.
  
• anti-androgen drugs:
  • non-steroidal e.g. flutamide - compete with androgens for binding sites at the androgen receptor. May cause a secondary increase in circulating testosterone as the negative feedback of androgens on the pituitary is blocked. Not used as first-line therapy. No clear-cut evidence that it is as effective in reducing mortality as other standard treatments.
  • steroidal e.g. cyproterone acetate - has additional progestational effects which inhibit gonadotrophin secretions and lower testosterone to castration levels.
    
• complete androgen blockade - surgical or medical castration is combined with an antiandrogen to block activity of testosterone derived from the adrenals. Under evaluation.
  
• bilateral total or subcapsular orchidectomy - eliminates the major source of testosterone.
  
• oral oestrogens - suppress serum testosterone levels to castrate levels. Act by a central mechanism blocking LHRH secretion. Stilboestrol at 3 mg daily is the usual regimen. The risk of thrombo-embolic complications has stopped their use as first-line therapy but may be lessened by combining with aspirin.