Long-Term Effect of a Luteinizing-Hormone-Releasing Hormone Analogue (Buserelin) on Cryptorchid Testes (Extended Summary)

F. Hadziselimovic, MD, University Children’s Hospital Basel, Römergasse 8, CH-4005 Basel (Switzerland) Cryptorchidism is a disorder of the hypothalamic-pituitary-gonadal axis and is not a malformation. We advocate early treatment (10 months of age) to avoid pronounced secondary gonadal changes starting after 12 months of age. The lower the testes are situated the better their histology; the younger the children are the more normal their gonads. During the 1st important months of life, transformation of gonocytes into spermatogonia takes place. This transformation is gonadotropinand testosterone-dependent and is impaired in cryptorchid boys. After the 2nd year of life, 38% of cryptorchid boys completely lack germ cells. This group of patients is therefore at risk of being sterile. Standard treatment with luteinizing-hormone-releasing hormone (LHRH) and human chorionic gonadotropin has proven successful in 74% of all boys treated [1]. An LHRH agonist analogue (Buserelin, Hoechst) is about 10 times more active than native LHRH and it has been shown to stimulate germ cell division if given after successful surgery for cryptorchidism [2]. The results of our study show for the first time that it is possible to increase the number of germ cells with hormonal therapy even when the testis is undescended [3]. This also provides additional support for the hypothesis that lack of germ cells in boys with cryptorchidism is due to impairment of the hypothalamic-pituitary-gonadal axis [4, 5] and not to high temperature or elevated pressure as generally believed. Furthermore, our previous studies have shown that buserelin treatment should be started early in life if an optimal response is to be achieved [2]. The lack of a good response in boys older than 7 years could be explained by the secondary changes that are already significant by the age of 2 years [6, 7]. Therefore, hormonal and surgical treatment should be initiated before the age of 12 months. No side effects and particularly no down-regulation of the hypothalamic-pituitary-gonadal axis occurred during treatment with buserelin. In older boys low doses of buserelin given on alternate days induced a low but significant increase in testosterone, indicating a stimulatory effect of gonadotropins on the Leydig cells [3]. This effect was not observed in the urine of young boys with cryptorchidism despite the fact that Leydig cell number increased indicating an augmentation of intratesticular testosterone. However, until further controlled studies have confirmed our findings treatment with Buserelin should be given only after orchio-pexy in those boys whose germ cell number is lower than 0.1 germ cell per tubular cross section. References