Hypospadias

Hypospadias is a male birth defect in which the opening of the tube that carries urine from the body (urethra) develops abnormally, usually on the underside of the penis, anywhere from below the end of the penis to the scrotum. Instead of opening at the tip of the glans of the penis, a hypospadic urethra opens anywhere along a line (the urethral groove) running from the tip along the underside (ventral aspect) of the shaft to the junction of the penis and scrotum or perineum.

Hypospadias are among the most common birth defects of the male genitalia (second to cryptorchidism), but widely varying in incidence. The incidence of hypospadias around the world has been increasing in recent decades. In the United States, two surveillance studies reported that the incidence had increased from about 1 in 500 total births (1 in 250 boys) in the 1970s to 1 in 250 total births (1 in 125 boys) in the 1990s. Although a slight worldwide increase in hypospadias was reported in the 1980s, studies in different countries and regions have yielded conflicting results and some registries have reported decreases.

A distal hypospadias may be suspected even in an uncircumcised boy from an abnormally formed foreskin and downward tilt of the glans.

The urethral meatus opens on the underside of the glans penis and on the penile body in about 50-75% of cases; these are categorized as distal forms. Proximal forms (when the urethra opens on the shaft starts from the penoscrotal angle to the perineum), occur in up to 20 and 30% of cases. The more severe degrees are more likely to be associated with chordee, in which the phallus is incompletely separated from the perineum or is still tethered downwards by connective tissue, or with undescended testes (cryptorchidism).

Associated anomalies

Mild hypospadias most often occurs as an isolated birth defect without detectable abnormality of the remainder of the reproductive or endocrine system. However, a minority of infants, especially those with more severe degrees of hypospadias will have additional structural anomalies of the genitourinary tract. Up to 10% of boys with hypospadias have at least one undescended testis, and a similar number have an inguinal hernia. An enlarged prostatic utricle is common when the hypospadias is severe (scrotal or perineal), and can predispose to urinary tract infections, pseudo-incontinence, or even stone formation.

Etiology

In most cases, the cause of this birth defect is not fully understood. Treatment with hormones such as progesterone during pregnancy may increase the risk of hypospadias. Certain hormonal fluctuations, such as failure of the fetal testes to produce enough testosterone or the failure of the body to respond to testosterone, increase the risk of hypospadias and other genetic problems. Sometimes hypospadias is inherited.

There also may be an increased risk of hypospadias in male infants from late pregnancy or those conceived with in vitro fertilization (IVF). Correlation with IVF may be due to the mother’s exposure to progesterone, a natural hormone, or to progestin, a synthetic form of progesterone, administered during the IVF process.

Prenatal testosterone, converted in the genital skin to dihydrotestosterone, causes migration of skin fibroblasts to fully enclose the urethral groove in fetal males, normally resulting in an enclosed penile urethra by the second trimester of pregnancy. Failure of adequate prenatal androgen effect is therefore thought to be involved in many cases, making severe hypospadias a very mild form of intersex (under-virilization of a genetic male). Since postnatal androgen deficiency can only be demonstrated in a minority of cases, it has been proposed that transient deficiency of testosterone can occur during critical periods of fetal genital development, due to elevation of anti-müllerian hormone or more subtle degrees of pituitary-gonadal dysfunction. More recently, abnormalities of transcription factors have been proposed.

In a minority of cases, a postnatal deficiency of androgens, or reduced sensitivity to androgens (testosterone and dihydrotestosterone) can be demonstrated. These are often associated with a chordee, and in severe cases a residual perineal urogenital opening and small phallus. This combination of birth defects is referred to as pseudovaginal perineoscrotal hypospadias and is a part of the spectrum of ambiguous genitalia. Postnatal testosterone treatment does not close the urethra. Genetic factors are likely involved in at least some cases, as there is about a 7% familiar recurrence risk. A 2010 Article found a 2.5 times increase in the condition for boys with a specific genetic defect that was carried on the X (maternally contributed sex) chromosome.

Treatment

Distal forms (glanular, subglanular, midshaft) are repaired between 12 and 18 months of age. There are more than 200 operative techniques and their modifications. Success rate is approximately 90 to 95%. Surgical repair of distal hypospadias is almost always successful after a single procedure, usually performed by a pediatric urologist or a plastic surgeon until the child is one year old.

When the hypospadias is severe degree, or there are associated birth defects such as chordee or cryptorchidism, the best management can be more complicated. A karyotype and endocrine evaluation should be performed to detect intersex conditions or hormone deficiencies. If the penis is small, testosterone or human chorionic gonadotropin (hCG) injections may be given to enlarge it prior to surgery. Surgical repair of severe hypospadias may require multiple procedures and mucosal grafting. Preputial skin is often used for grafting and circumcision should be avoided prior to repair.

Complications and secondary repair

In a minority of patients with severe hypospadias surgery produces unsatisfactory results, such as scarring, curvature, or formation of urethral fistulas, diverticula, or strictures. A fistula is an unwanted opening through the skin along the course of the urethra, and can result in urinary leakage or an abnormal stream. A diverticulum is an “outpocketing” of the lining of the urethra which interferes with urinary flow and may result in post-urination leakage. A stricture is a narrowing of the urethra severe enough to obstruct flow. Reduced complication rates even for third degree repair (e.g., fistula rates below 5%) have been reported in recent years from centers with the most experience, and surgical repair is now performed for the vast majority of infants with hypospadias. Special problem presents urethral complications in adulthood, after primary repaired hypospadias in childhood. In these cases, standard principles for urethral reconstruction in adults should be performed for successful outcome.