Purpose: Hypospadias is a common congenital anomaly that may be treated with surgical reconstruction. In the majority of cases the etiology remains elusive. Although androgens are clearly critical for penile development, defects in androgen metabolism and/or the androgen receptor explain only a small subset of cases of hypospadias. Strategies are presented for understanding the etiology of hypospadias.
Materials and methods: Current scientific reports on the etiology of hypospadias were reviewed, and the embryology and possible mechanisms of urethral and penile formation are presented.
Results: A new theory of glandular human urethral development via endodermal cellular differentiation is proposed to replace the classic explanation of ectodermal intrusion.
Conclusions: Careful studies of penile and urethral development have led to a better understanding of genital embryology. Future areas of study, such as endocrine disrupters, mesenchymal-epithelial interactions and mechanisms of penile growth, are proposed to explain the etiology of hypospadias.