Testicular dysgenesis syndrome comprises some but not all cases of hypospadias and impaired spermatogenesis

Summary In 2001, when the testicular dysgenesis syndrome (TDS) concept was proposed, it suggested that impaired development of foetal testes could lead to increased risks of cryptorchidism, hypospadias, decreased spermatogenesis or testis cancer. The TDS concept links the pathogenesis of the four disorders together, but does not imply that all affected men develop all four symptoms. The least affected men may merely have a slightly reduced spermatogenic capacity, and only the most severely affected may present all symptoms. A majority of cases of testicular germ cell cancers (TGCC) and cryptorchidism are most likely caused by TDS. However, the frequency of the syndrome in the general population and to what extent poor semen quality and hypospadias are actually biologically related through a foetal mechanism remain unresolved. Hypospadias and impaired spermatogenesis can be classified as TDS if combined with cryptorchidism or TGCC. By contrast, recent studies demonstrated that among men with isolated hypospadias, only a fraction of cases are linked to TDS. There is no doubt that TDS contributes to impaired semen quality. This is most obvious for cases with visible dysgenetic features in testis histology, but in the majority of men with impaired semen quality as the only symptom, an association with TDS is less clear. Such cases have a very heterogeneous aetiology and may be caused by a host of other – often post‐natal‐factors. In conclusion, the TDS as a holistic concept has inspired new research activities and led to a better understanding of the early origin of male reproductive problems, but it clearly encompasses only a fraction of cases of hypospadias and impaired spermatogenesis.