What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis

It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity—the testicular dysgenesis syndrome—leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease.