Swerdloff R S, Steiner B S, Bhasin S
Med Biol. 1986;63(5-6):218-24.
A potent gonadotropin releasing hormone (GnRH) agonist, D(Nal2)6 GnRH (Nafarelin) has been administered to two groups of normal men for 16 weeks by two routes in order to assess its effectiveness in suppressing spermatogenesis. In this report 400 micrograms of the GnRH agonist was given daily by constant subcutaneous infusion and the results compared to an earlier study in which 200 micrograms of the same agonist was given as a single daily subcutaneous injection. All subjects in both groups received an intramuscular injection of testosterone enanthate (200 mg) every two weeks to prevent symptoms of androgen deficiency. The higher dose infusion regimen was much more effective in suppressing spermatogenesis than the single daily injection. With infusion treatment, 3 of 7 subjects were azoospermic, a fourth subject had less than 1 million sperm per ml of semen and 5 of 7 subjects had sperm counts less than 5 million per ml. Because of the differences in GnRH dose it is unclear if the enhanced effect seen in the infusion group is the result of the route or dose of drug. Data from experimental animals and short term comparative studies with two routes and two doses suggest that both mechanisms may be operative. In either case, the results are the most promising to date and raise the possibility that constant delivery of a higher dosage of agonist could produce azoospermia in most or all subjects.
一种强效促性腺激素释放激素（GnRH）激动剂，即D（Nal2）6 GnRH（那法瑞林），通过两种途径对两组正常男性给药16周，以评估其抑制精子发生的有效性。在本报告中，通过持续皮下输注每天给予400微克GnRH激动剂，并将结果与早期一项研究进行比较，在该研究中，每天皮下注射一次200微克相同的激动剂。两组的所有受试者每两周接受一次庚酸睾酮（200毫克）肌肉注射，以预防雄激素缺乏症状。高剂量输注方案在抑制精子发生方面比每日单次注射有效得多。采用输注治疗时，7名受试者中有3名无精子症，第四名受试者每毫升精液中的精子数少于100万个，7名受试者中有5名精子计数少于每毫升500万个。由于GnRH剂量不同，尚不清楚输注组中观察到的增强效果是给药途径还是药物剂量的结果。来自实验动物的数据以及两种途径和两种剂量的短期比较研究表明，两种机制可能都起作用。无论哪种情况，这些结果都是迄今为止最有前景的，并增加了持续给予更高剂量激动剂可能使大多数或所有受试者产生无精子症的可能性。
