Last updated: 02/17/2009

Hypospadias is much more common in males than in females. In Canada and the United States, the incidence of hypospadias in boys is estimated to be 1:250 or 1:300 live births. In girls, the condition is very rare, estimated at 1:500,000 live births....

One troubling phenomenon is the reported doubling of cases of hypospadias in both Europe and North America since the 1970s without any obvious explanation. According to a recent press release from the U.S. Centers for Disease Control and Prevention (CDC), data from two surveillance systems monitoring birth defects in the United States show that the rate of hypospadias rose from 36 per 10,000 male births in 1968 to 80 per 10,000 male births in 1993. In addition to the increase in the number of cases reported, the proportion of severe cases has also risen, which means that the numerical increase cannot be explained as the result of better reporting.

The severity of hypospadias is defined according to the distance of the urethral opening from its normal location at the tip of the penis. In mild hypospadias, which is sometimes called coronal/glandular hypospadias, the urethral opening is located on the shaft of the penis just below the glans. In mild to moderate hypospadias, the opening is located further down the shaft of the penis toward the scrotum. In severe hypospadias, which is also called penoscrotal hypospadias, the urethral opening is located on the scrotum. About 80–85% of hypospadias are classified as mild; 10–15% as mild to moderate; and 3–6% as severe.

Although the causes of hypospadias are not yet fully understood, the condition is thought to be the end result of a combination of factors. The following have been associated with an increased risk of hypospadias:

• Genetic inheritance. Hypospadias is known to run in families; a boy with hypospadias has a 28% chance of having a male relative with the condition.
• Genetic disorders. Hypospadias is found in boys with a deletion on human chromosome 4p, also known as Wolf-Hirschhorn syndrome; and in persons with a variety of intersex conditions related to chromosomal abnormalities. Several different genetic mutations responsible for a deficiency in 5-alpha reductase, an enzyme needed to convert testosterone to a stronger androgen needed for urethral development, have been found in boys with hypospadias.
• Low birth weight. Several studies in the United Kingdom as well as in the United States have shown that male infants with hypospadias weigh less and are smaller at birth than controls. It is thought that these low measurements are markers of fetal androgen dysfunction.
• Drugs taken by the mother during pregnancy. Diethylstilbestrol (DES), a synthetic hormone that was prescribed for many women between 1938 and 1971 to prevent miscarriage, has been associated with an increased risk of stenosis of the urethral meatus as well as hypospadias in the sons of women who took the medication. Boys born to mothers addicted to cocaine also have an abnormally high rate of hypospadias.
• Environmental contamination. One proposal for explaining the rising rate of hypospadias and other birth defects in males is the so-called endocrine disruptor hypothesis. Many pesticides, fungicides, and other environmental pollutants contain estrogenic or anti-androgenic substances that interfere with the normal androgen pathways in embryonic tissue development—in birds and other animals as well as in humans.
• Assisted reproduction. A study done in Baltimore of children who were conceived through in vitro fertilization (IVF) between 1988 and 1992 found that the incidence of hypospadias among the males was five times that of male infants in a control group.

With regard to ethnic and racial differences in the American population, the CDC reports that Caucasians have the highest rates of hypospadias, Hispanics have the lowest, and African Americans have intermediate rates. Other studies have found that hypospadias is more common in males of Jewish or Italian descent than in other ethnic groups.