Antifertility effects of LHRH agonists in the male rat and inhibition of testicular steroidogenesis in man.

Acute or chronic treatment of adult male rats with luteinizing hormone-releasing hormone (LHRH) or its agonist leads to a loss of testicular LH and prolaction receptors accompanied by decreased testis seminal vesicle and ventral prostate weight. The inhibition of testosterone formation is due to a blockage of the steroidogenic pathway at the level of 17-hydroxylase and 1720-desmolase activities. The testicular desensitization is accompanied by a decreased pituitary responsiveness LHRH. Although the inhibitory effects at the testicular level could be explained by endogenous LH release induced by the LHRH agonist with secondary testicular desentization the LH-relasing peptides also exert direct inhibitory effects on gonadotropin receptors at the testicular level. Moreover LHRH and its agonists bind to a specific LHRH receptor in interstitial cells. Chronic treatment with LH agonists leads to marked degenerative changes in the seminiferous tubules almost all tubules showing signs of histologic damage after 4 weeks of treatment. Single administration of an LHRH agonist by the intranasal route in normal adult men casuses a transient inhibition of plasma testosterone levels with a temporary loss of diurnal cyclicity whereas preliminary data obtained in patients with cancer of the prostrate show inhibition of both testosterone and dihydrotestosterone plasma levels. Such data suggest the potential use of LHRH agonists in male contraception and for the treatment of cancer of the prostrate. (authors)