Faure N, Lemay A
Arch Androl. 1985;14(2-3):95-106. doi: 10.3109/01485018508988284.
The antireproductive properties of LHRH and its agonists have now been clearly established. Using various dosing regimens and routes of administration in animal experiments and in clinical trials, these peptides invariably produce paradoxical inhibitory effects on reproductive function. This ability led to the concept that gonadal steroid-dependent (responsive) tumors might also be affected in a manner analogous to that produced by gonadectomy or by antiandrogenic or antiestrogenic drugs. Numerous data have now appeared in the medical literature on the potential efficacy of the LHRH agonists as a tumor therapy. Using different agonists (D-Ser6, D-Leu6 and D-Trp6-LHRH) and various dosages, the investigators were successful in inducing a "medical castration" with androgen levels comparable to castrate control subjects. Objective tumor regression and significant clinical improvement paralleled the hormonal suppression shown in our studies and by other groups. Another interesting potential clinical application of the ability of LHRH agonist to inhibit testicular function is its development as a male contraceptive. This approach is being tested by a few groups. In order to preserve potency, exogenous androgens must be administered with the agonist. Long-term pituitary suppression in boys with idiopathic precocious puberty has now been achieved and premature sexual development suppressed. In man the main mechanism responsible for testicular inhibition seems to be the achievement of a temporary and reversible state of hypogonadotropic hypogonadism. Recent data show that LHRH agonist alters the ratio of bioactive and immunoreactive LH and suggest a direct effect on LH biosynthesis as a mechanism of action of LHRH agonist analogs. Other findings support the lack of direct effect of LHRH agonist on Leydig cells in humans. In view of the main potential clinical applications--as therapy for chronic hormone-dependent disease or as a male contraception--major new developments are being undertaken in the way of administration of these substances by slow delivery systems.
促黄体生成素释放激素（LHRH）及其激动剂的抗生殖特性现已明确。在动物实验和临床试验中，通过使用各种给药方案和途径，这些肽对生殖功能总是产生矛盾的抑制作用。这种能力引发了一种概念，即性腺类固醇依赖（反应性）肿瘤也可能受到类似于性腺切除术或抗雄激素或抗雌激素药物所产生的影响。关于LHRH激动剂作为肿瘤治疗的潜在疗效，医学文献中现已出现大量数据。研究人员使用不同的激动剂（D - 丝氨酸6、D - 亮氨酸6和D - 色氨酸6 - LHRH）和各种剂量，成功诱导出“药物去势”，其雄激素水平与去势对照组相当。客观的肿瘤消退和显著的临床改善与我们的研究以及其他研究组所显示的激素抑制情况相平行。LHRH激动剂抑制睾丸功能的能力的另一个有趣的潜在临床应用是将其开发为男性避孕药。有几个研究组正在对这种方法进行测试。为了保持性功能，必须与激动剂一起给予外源性雄激素。现已实现对特发性性早熟男孩的长期垂体抑制，并抑制了过早的性发育。在人类中，导致睾丸抑制的主要机制似乎是实现了一种促性腺激素缺乏性性腺功能减退的暂时和可逆状态。最近的数据表明，LHRH激动剂改变了生物活性和免疫反应性促黄体生成素（LH）的比例，并提示对LH生物合成有直接影响，这是LHRH激动剂类似物的作用机制。其他研究结果支持LHRH激动剂对人类睾丸间质细胞缺乏直接作用。鉴于主要的潜在临床应用——作为慢性激素依赖性疾病的治疗或作为男性避孕——正在通过缓释系统对这些物质的给药方式进行重大新进展的研究。
