What is the etiology of hypospadias? A review of recent research.

The multi-factorial etiology of hypospadias is becoming more defined with ongoing investigation. Implicated factors include testosterone biosynthesis defects, 5 alpha-reductase type 2 mutations, androgen receptor mutations (rare), IVF (progesterone administration or endocrine abnormalities associated with infertility), and environmental agents that can disrupt the male sex hormone axis. It also seems that the incidence of hypospadias is on the rise, both in the United States and in Europe. Hypospadias is a physical manifestation that may be a consequence of numerous physiological aberrations, and our ability to understand and to potentially prevent this problem will require a significant amount of additional work. Our challenge for the future remains to identify the various etiologies, provide prenatal counseling for affected families with a history of hypospadias, and minimize or eliminate exposure to environmental agents that may contribute to this problem. It is even possible that some day we may be able to offer prenatal therapy to prevent hypospadias when the risk for this birth defect seems high. Does this sound far-fetched? Consider the modern management of a family with a child born with the adrenogenital syndrome, another endocrine derangement that can cause abnormal genital development. In this situation, dexamethasone can be administered to the mother in subsequent pregnancies to prevent fetal virilization until the sex of the fetus can be determined or adrenal enzyme mutations can be excluded. Perhaps in the future a similar approach will be taken for those families with strong risk factors for hypospadias.