Endocrine abnormalities in boys with hypospadias

Abstract

The multifactorial etiology of hypospadias is becoming more clearly defined with ongoing investigation. Endogenous endocrine abnormalities identified so far include testosterone biosynthesis defects, 5alpha-reductase type 2 mutations, and androgen receptor mutations (the rarest cause, even in cases of severe hypospadias). Other significant risk factors include IVF (because of progesterone administration or endocrine abnormalities associated with infertility) and environmental agents that can potentially cause testicular dysgenesis, disrupt the male androgen axis, and disturb normal male genital embryology (Table 6). [table; see text] It also seems that the incidence of hypospadias is increasing, both in the United States and in Europe--which may be due to better medical care for those with genital abnormalities and/or infertility problems, as well as environmental endocrine disruptors. Hypospadias is a physical manifestation that may be a consequence of numerous physiological aberrations, and our ability to understand and to potentially prevent this congenital malformation 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. Perhaps one day we will be able to offer prenatal therapy to prevent hypospadias when the risk for this birth defect seems high. How might this be possible? 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.