GONADOTROPIN-RELEASING-HORMONE AND ITS ANALOGS

GnRH and its analogues have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gyneco logy, pediatrics, and urology. Since their discovery in 1971, it has b een demonstrated that GnRH and its analogues enable medical profession als to influence the hypothalamic-pituitary-gonadal axis in two distin ct classes of therapeutic applications. The first provides natural seq uence GnRH in a pulsatile fashion via portable infusion pumps to mimic the normal physiology of hypothalamic GnRH secretion and restores rep roductive potential to infertile men and women with disorders of endog enous GnRH secretion. The second mode uses long-acting GnRH agonists a dministered in a depot delivery to produce a paradoxical desensitizati on of pituitary gonadotropin secretion which, in turn, results in a co mplete ablation of the reproductive axis. This biochemical castration induced by GnRH agonist administration is a safe, effective, complete, and reversible method of removing the overlay of gonadal steroids fro m a variety of diseases which they are known to exacerbate. These dise ases include endometriosis and uterine fibroids in women, prostate can cer in men, and precocious puberty in both sexes. This review examines the physiologic and pharmacologic principles underlying the advances produced by these agents, the mechanism of action of GnRH and its anal ogues at the cellular level, and the individual therapeutic applicatio ns to which these analogues have been applied. Because virtually every subspecialty of medicine will be touched by the GnRH analogues, this review provides an overview and background of their use.