Fraser H M
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
Br Med Bull. 1993 Jan;49(1):62-72. doi: 10.1093/oxfordjournals.bmb.a072606.
The production of chemical analogues of GnRH permits direct suppression of the pituitary-gonadal axis at the level of the gonadotroph. Continuous administration of GnRH agonists desensitizes the gonadotroph and ovulation is uniformly prevented, forming the practical basis for use in contraception. However, long-term treatment is constrained by variable effects on oestrogen secretion, which cause irregular bleeding patterns on the one hand and risks of hypo-oestrogenism on the other. Their use as a post-partum contraceptive has attractions because any analogue in milk should be without biological activity in the infant. GnRH antagonists have the advantage of immediate inhibitory action. They have potential application in circumstances in which agonists have been employed and, in addition, can interrupt any stage of the menstrual cycle. Clinical trials to utilise their potential antifertility action have not been performed. Use of GnRH analogues for contraception in women may require combination with low dose oestrogen and progestin and it has been proposed that such development may yield important benefits in health. When combined with testosterone, GnRH antagonists may form the basis for a male contraceptive.
促性腺激素释放激素(GnRH)化学类似物的产生使得能够在促性腺激素细胞水平直接抑制垂体 - 性腺轴。持续给予GnRH激动剂会使促性腺激素细胞脱敏,并一致地阻止排卵,这构成了其用于避孕的实际基础。然而,长期治疗受到对雌激素分泌的可变影响的限制,一方面会导致不规则出血模式,另一方面会有低雌激素血症的风险。它们作为产后避孕药具具有吸引力,因为乳汁中的任何类似物对婴儿都应无生物活性。GnRH拮抗剂具有立即抑制作用的优势。它们在已使用激动剂的情况下有潜在应用,此外,还可中断月经周期的任何阶段。尚未进行利用其潜在抗生育作用的临床试验。在女性中使用GnRH类似物进行避孕可能需要与低剂量雌激素和孕激素联合使用,并且有人提出这种发展可能会带来重要的健康益处。当与睾酮联合使用时,GnRH拮抗剂可能构成男性避孕药的基础。