Hypospadias

Updated: Jun 16, 2019
  • Author: John Michael Gatti, MD; Chief Editor: Marc Cendron, MD  more...
  • Print
Overview

Background

Hypospadias is an abnormality of anterior urethral and penile development. The urethral opening is ectopically located on the ventral aspect of the penis proximal to the tip of the glans penis, which, in this condition, is splayed open. [1] The urethral opening may be located as proximal as in the scrotum or perineum. The penis will commonly have associated ventral shortening and curvature, called chordee, with more proximal urethral defects.

Galen, in the second century CE, may be credited with the earliest medical text to use the term hypospadias. During the first millennium, the primary treatment for hypospadias was amputation of the penis distal to the meatus. Since that time, surgical repair has progressed in relation to advances in surgical instruments, introduction of anesthesia, and innovation in suture material. Stretching the urethra gave way to tunneling procedures and, ultimately, to flaps and tubularization in the modern era.

Many have contributed to development of modern hypospadias repair. More than 300 different types of repairs have been described in the medical literature. Although most reports have been in the past 60 years, most basic techniques were described more than a century ago. [2]

Modern anesthetic techniques, fine instrumentation, sutures, dressing materials, and antibiotics have improved clinical outcomes and have, in most cases, allowed surgical treatment with a single-stage repair within the first year of life on an outpatient basis.

Next:

Pathophysiology

Hypospadias is a congenital defect that is thought to occur during the embryologic development of the urethra, between 8 and 20 weeks' gestation. The external genital structures are identical in males and females until 8 weeks, after which time the genital structures develop a masculine phenotype in males, primarily under the influence of testosterone and its byproduct dihydrotestosterone. As the phallus grows, the open urethral groove extends from its base to the level of the corona.

The classic theory is that the urethral folds coalesce in the midline from base to tip, forming a tubularized penile urethra and median scrotal raphe. This accounts for the posterior and middle urethra. The anterior or glanular urethra is thought to develop in a proximal direction, with an ectodermal core forming at the tip of the glans penis, which canalizes to join with the more proximal urethra at the level of the corona. The higher incidence of subcoronal hypospadias supports the vulnerable final step in this theory of development.

In 2000, Baskin proposed a modification of this theory in which the urethral folds fuse to form a seam of epithelium, which is then transformed into mesenchyme and subsequently canalizes by apoptosis or programmed cell resorption. [3] Similarly, this seam theoretically also develops at the glanular level, and the endoderm differentiates to ectoderm with subsequent canalization by apoptosis.

The prepuce normally forms as a ridge of skin from the corona that grows circumferentially, fusing with the glans. Failure of fusion of the urethral folds in hypospadias impedes this process, and a dorsal hooded prepuce results. On rare occasions, a glanular cleft with intact prepuce may occur, which is termed the megameatus intact prepuce (MIP) variant.

Ventral curvature of the penis, termed chordee, is often associated with hypospadias, especially in more severe forms. This is thought to result from a growth disparity between the normal dorsal tissue of the corporal bodies and the attenuated ventral urethra and associated tissues. The abortive spongiosal tissue and fascia distal to the urethral meatus may form a tethering fibrous band that contributes to the ventral curvature. This can range from mild to very severe (90º angle). (See the image below.)

Severe penile chordee. Note extreme ventral curvat Severe penile chordee. Note extreme ventral curvature of penile shaft.

The location of the abnormal urethral meatus classifies the hypospadias. Although several different classifications have been described, most physicians use the one proposed by Barcat and modified by Duckett, which describes the location of the meatus after correction of any associated chordee. [4, 5] Descriptive locations in this classification include the following:

  • Anterior (glanular and subcoronal)
  • Middle (distal penile, midshaft, and proximal penile)
  • Posterior (penoscrotal, scrotal, and perineal)

The location is anterior in 50% of cases, middle in 20%, and posterior in 30%; the subcoronal position is the most common overall. (See the images below.)

Proximal shaft hypospadias. Note deficient ventral Proximal shaft hypospadias. Note deficient ventral foreskin, blind urethral pit at glanular level, and lighter pigmented urethral plate extending to true meatus at proximal shaft level.
Proximal shaft hypospadias. Note typical dorsal ho Proximal shaft hypospadias. Note typical dorsal hood of foreskin and ventral penile skin deficiency.
Penoscrotal hypospadias. Note associated ventral c Penoscrotal hypospadias. Note associated ventral chordee and true urethral meatus located at scrotal level.
Previous
Next:

Etiology

Several etiologies for hypospadias have been suggested, including genetic, endocrine, and environmental factors.

Genetic factors

A genetic predisposition has been suggested by the eightfold increase in incidence of hypospadias among monozygotic twins as compared with singletons. This finding may relate to the demand of two fetuses for human chorionic gonadotropin (HCG) produced by a single placenta, with an inadequate supply during critical periods of urethral development.

A familial trend has been noted with hypospadias. The prevalence of hypospadias in male children of fathers with hypospadias has been reported as 8%, and 14% of brothers of children with hypospadias are also affected. The inheritance is likely polygenic.

Endocrine factors

A decrease in available androgen or an inability to use available androgen appropriately may result in hypospadias. In a 1997 report by Aaronson et al, 66% of boys with mild hypospadias and 40% with severe hypospadias were found to have a defect in testicular testosterone biosynthesis. [6]

Mutations in the 5-alpha reductase enzyme, which converts testosterone (T) to the more potent dihydrotestosterone (DHT), have been associated with hypospadias. A 1999 report by Silver et al found that nearly 10% of boys with isolated hypospadias had at least one affected allele with a 5-alpha reductase mutation. [7]  Although androgen receptor deficits, quantitative or qualitative, have been shown to result in hypospadias, this is thought to be relatively uncommon, and other factors are more commonly implicated.

A higher incidence of hypospadias in winter conceptions has also been proposed. Theoretically, this may be related to the effect of daylight on pituitary function, which, in turn, affects the maternal and fetal hormonal milieu; however, other authors have not noticed this association.

A fivefold increased risk of hypospadias appears to exist in males born through in-vitro fertilization (IVF) in comparison with a control group. This may reflect maternal exposure to progesterone, which is commonly administered in IVF protocols. Progesterone is a substrate for 5-alpha reductase and acts as a competitive inhibitor of the T-to-DHT conversion.

Other factors that contribute to infertility, such as underlying endocrinopathies or fetal endocrine abnormalities, may play a role.

Environmental factors

Endocrine disruption by environmental agents is gaining popularity as a possible etiology for hypospadias and as an explanation for its increasing incidence.

Estrogens have been implicated in abnormal penile development in many animal models. Environmental substances with significant estrogenic activity are ubiquitous in industrialized society and are ingested as pesticides on fruits and vegetables, endogenous plant estrogens, in milk from lactating pregnant dairy cows, and in pharmaceuticals such as phthalates. The association of hypospadias with increasing parity, increasing maternal age, and low birth weight noted in some studies may reflect a lifelong exposure to environmental disruptors and a possible cumulative effect. [8]

Combination theory

A growing body of evidence suggests that the development of hypospadias has a two-hit etiology involving a genetic predisposition coupled with fetal exposure to an environmental disruptor. [9, 10]

Previous
Next:

Epidemiology

United States statistics

Hypospadias occurs in approximately 1 in every 250 male births in the United States. The incidence doubled from 1970 to 1993. Although some have suggested that this doubling actually reflects increased reporting of minor grades of hypospadias, increases in severe hypospadias were also noted. Increasing sensitivity of surveillance systems alone cannot explain this twofold increase. However, some reports linked the increased rate of hypospadias in boys born prematurely and small for gestational age and boys with low birth weight.

International statistics

In several countries, the incidence of hypospadias may be rising. In general, the frequency seems rather constant, at 0.26 per 1000 live births in Mexico and Scandinavia and 2.11 per 1000 live births in Hungary. [11]

Race-related demographics

The incidence of hypospadias is higher in whites than in blacks, and the condition is more common in those of Jewish and Italian descent. A genetic component may be present in certain families; the familial rate of hypospadias is about 7%.

Previous
Next:

Prognosis

With modern anesthetics, instruments, sutures, dressing materials, and antibiotics, hypospadias repair is considered generally successful. Earlier studies focused on outcome measures of cosmesis and low complication rates of urethrocutaneous fistula or dehiscence. Long-term studies on the outcomes of hypospadias with current practices are limited. 

Although some earlier studies have been discouraging, these reflect an era with poorer technical outcomes, an increased number of operations, and a lack of appreciation for the psychological morbidity associated with intervention at an older age. More severe forms of hypospadias may require long-term follow-up and multiple surgical procedures.

Subsequent long-term studies suggested that despite having decreased satisfaction with their genital appearance, patients who have undergone hypospadias repair are more satisfied with their sex lives in comparison with healthy control subjects. [12]  Newer scoring systems to lend an objective measure to long-term outcomes are becoming more popular. [13, 14]

Although the techniques of hypospadias repair continue to evolve, the broader future of hypospadias treatment is truly promising. Nontraditional tissue adherence techniques are being developed, including tissue glues and laser-activated soldering techniques that have been shown to improve wound healing and to reduce fistula formation.

Urethral substitutes, which may obviate the difficulties associated with severe hypospadias and poor tissue availability, are currently under investigation. These substitutes are generally acellular synthetic or natural matrices that can incorporate the patient's normal urethral cellular components.

Previous
Next:

Patient Education

Because most patients with hypospadias are surgically treated at a very young age, parental teaching and reassurance is very important to ensure a satisfactory experience for the families of these patients. Evidence suggests that online support groups can play an important role in how parents and patients cope with hypospadias. [15]

Previous