A Rotterdam controversy: the aetiology of the cryptorchid hypothalamo‐pituitary‐testicular axis

Abstract

Dear Sir, In their contribution, Pierik et al. (2008) found in 43 cryptorchid infants studied, testosterone and free-androgens deficiency indicating a disturbance of testicular function that was already evident early after birth. Twenty years earlier one of the co-authors in this paper analysed 48 cryptorchid infants and came to different conclusion that “during the first year of life boys with cryptorchidism have no functional insufficiency of hypothalamus-pituitary-testis axis (HPG) or disorders in testosterone biosynthesis” (De Muinck Keizer-Schrama et al., 1988). Surprisingly, no annotation regarding this controversy was made in their paper. We would question what has changed in the past 20 years that led them to this observation of Leydig cell dysfunction. Is the ethnic heterogeneity of cryptorchid boys responsible for the observation of the hypothalamo-pituitary-testicular axis insufficiency found in Turkish population? Or, could severity or bilaterality of cryptorchidism, which was not known for the majority of cases studied, be an explanation for the lower LH and FSH levels? During last 35 years it has been histology that contributed most in helping us to understand the aetiology of cryptorchidism. In 1975 we described pronounced Leydig cell atrophy starting in early infancy as the evidence to support the endocrinopathy as an etiologic factor of cryptorchidism (Hadziselimovic et al., 1975). Development of Ad spermatogonia from gonocytes, which takes place during first months of life, has been shown to be testosterone dependent and is disturbed in the majority of cryptorchid boys (Hadziselimovic et al., 2005; Zivkovic et al., 2007). Analysis of the contralateral descended testis in unilateral cryptorchidism demonstrated that cryptorchidism is a bilateral disease (Hadziselimovic et al., 2005; Zivkovic et al., 2007; Huff et al., 2001). Therefore, an examination of histology at the time of orchidopexy could help authors to better understand hypogonadotropic hypogonadism and explain the different ethnical observations.