Clinical applications of LHRH analogues.

What is the current state of clinical application of inhibition of gonadal activity with LHRH agonists or antagonists? It seems unlikely in the short term that antagonists will be widely applied due to the short-acting nature of the present compounds and their troublesome side-effects. In contrast clinical studies with a number of agonists have demonstrated their efficacy in producing a hypogonadal state safely with rapid recovery following cessation of therapy. Although nasal administration may be suitable for short-term suppression (up to 28 days) it seems likely that long-acting depot preparations will be useful for more prolonged suppression. Perhaps the easiest application to determine will be the profound suppression required to produce medical castration in hormone-dependent tumours. The combination of agonist and receptor blocker is attractive particularly when the receptor blocker like cyproterone acetate also suppresses the release of LH, FSH and adrenocorticotrophic hormone. In cancer of the prostate and breast the side-effects due to inhibition of secretion of testosterone and oestradiol are tolerable although the only benefit over castration is the avoidance of minor surgery. The agonists should improve significantly the existing treatment for precocious puberty, endometriosis, uterine fibroids, polycystic ovary syndrome (PCO) and induction of ovulation although large scale trials comparing different therapies and doses are required. Finally, the concept of combination therapies to block further the influence of steroid hormones suggests challenging possibilities for even more effective therapy.