Is the prohibition of hormonal treatment for cryptorchidism, as suggested by the Nordic consensus group, justifiable?

Abstract

Recently, the Nordic consensus on the treatment of undescended testis prohibited the use of hormones because of possible long-term adverse effects on spermatogenesis (1). This conclusion was based on articles published by groups from Finland and Denmark analyzing testicular histology and apoptosis of the germ cells (1). Even if human chorionic gonadotropin (HCG) treatment induces increased apoptosis of the germ cells, it is still irrelevant for subsequent fertility outcome. The follow-up spermiogram performed in these patients showed no significant difference in fertility outcome between the treated and untreated groups. The second reason was the observation of decreased numbers of germ cells in cryptorchid boys aged 1–3 years who were previously unsuccessfully treated with HCG in comparison to the untreated group (1). These results, although statistically significant, are again irrelevant for the fertility outcome because the germ cell count in both groups was below 0.2 germ cells per tubular cross-section. If the germ cell count is <0.2, the majority of patients will develop infertility irrespective of whether they had only surgery or hormonal pretreatment in addition to orchidopexy. Abnormal contralateral testis is ideal for evaluating the effect of hormonal treatment because there is no effect from abnormal position and increased temperature to interfere with the results. In contrast to the concerns raised by the Nordic consensus group, the results of our recent study showed that hormonal treatment for undescended testis improved the histopathology of the contralateral testis without harming the germ cells (2). Furthermore, neoadjuvant gonadotropin relasing hormone (GNRH) treatment was found to improve the fertility index in prepubertal cryptorchidism (3). Maximum salvage of active germinal tissue is achieved by treating cryptorchidism before the end of the first year of life (3). We entirely agree with the Nordic consensus group that infertility is the primary concern for the treatment of boys with unilateral or bilateral undescended testes. This especially because analysis of contralateral descended testis in unilateral cryptorchidism demonstrated that cryptorchidism is a bilateral disease, and infertility in cryptorchidism is endocrinopathy of mini-puberty (4,5). It is important to realize that male fertility potential depends on the presence of Ad spermatogonia (5–7). Development of Ad spermatogonia from gonocytes, which takes place during first months of life, was shown to be testosterone dependent (8). However, early and seemingly successful orchidopexy does not improve fertility in a substantial number of cryptorchid males because it does not address the underlying pathophysiology of cryptorchidism, namely, the impaired transformation of gonocytes into Ad spermatogonia (6,7). Furthermore, successfully surgically treated patients at risk for infertility after 6 months of luteinizing hormonerelasing hormone analogue (LH-RHa) treatment had a lasting increase in the number of germ cells in their cryptorchid testis (9). The efficacy of the LH-RHa treatment was the best in boys younger than 7 years (9,10). Treatment with LH-RHa normalized sperm concentration in 86% of unilateral cryptorchid males, who were in the high-risk group for developing infertility (Fig. 1). All males in the untreated group (surgery only) were severely oligospermic, with 20% being azoospermic (10). This profoundly changes our current concept of cryptorchidism treatment. For the first time, it is possible to demonstrate that infertility caused by cryptorchidism, which is believed to be a congenital malformation, can be successfully corrected if adequately treated. During the last 35 years, histological studies have contributed the most to our understanding of the aetiology of cryptorchidism. Only the comparison of histology and hormonal levels exemplify hypogonadotropic hypogonadism in the majority of cryptorchid boys. Why the Nordic consensus group did not take the histopathologic findings into consideration remains unclear. Nonetheless, their recommendation as to when a testicular biopsy should be obtained is passe. A testicular biopsy is the only sure way of identifying those cryptorchid boys who need to be treated hormonally with LH-RHa following successful surgery;