Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): environmental connection

Abstract

Cryptorchidism and hypospadias are common genital birth defects that affect 2-9% and 0.2-1% of male newborns, respectively. The incidence of both defects shows large geographic variation, and in several countries increasing trends have been reported. The conditions share many risk factors, and they are also interlinked to the risk of testis cancer and poor semen quality. Testicular Dysgenesis Syndrome (TDS) may underlie many cases of all these male reproductive health problems. Genetic defects in androgen production or action can cause both cryptorchidism and hypospadias, but these are not common. A monogenic reason for cryptorchidism or hypospadias has been identified only in a small proportion of all cases. Environmental effects appear to play a major role in TDS. Exposure to several persistent chemicals has been found to be associated with the risk of cryptorchidism, and exposure to anti-androgenic phthalates has been shown to be associated with hormonal changes predisposing to male reproductive problems. Despite progress in identification of endocrine-disrupting substances, we are still far from knowing all the risk factors for these birth defects, and advice for prevention must be based on precautionary principles.