Background

Hypospadias is an abnormality of anterior urethral and penile development in which the urethral opening
is ectopically located on the ventrum of the penis proximal to the tip of the glans penis, which, in this
condition, is splayed open. The urethral opening may be located as far down as in the scrotum or
perineum. The penis is more likely to have associated ventral shortening and curvature, called chordee,
with more proximal urethral defects.
The earliest medical text describing hypospadias dates back to the second century AD and was the work
of Galen, the first to use the term. During the first millennium, the primary treatment for hypospadias was
amputation of the penis distal to the meatus. Since that time, many have contributed to development of
modern hypospadias repair. Over 300 different types of repairs have been described in the medical
literature. Although most reports have been in the last 60 years, most basic techniques were described
over a century ago.
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.
Pathophysiology
Hypospadias is a congenital defect that is thought to occur embryologically during urethral development,
from 8-20 weeks' gestation. The external genital structures are identical in males and females until 8
weeks' gestation; the genitals develop a masculine phenotype in males primarily under the influence of
testosterone. 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.
[1]
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.
Chordee, or ventral curvature of the penis, is often associated with hypospadias, especially 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. Rarely, the abortive spongiosal tissue
and fascia distal to the urethral meatus forms a tethering fibrous band that contributes to the chordee.
See the image below.
Severe penile chordee is shown. Note the extreme ventral curvature of the penile
shaft.
The location of the abnormal urethral meatus classifies the hypospadias. Although several different
classifications have been described, most physicians use the classification that was proposed by Barcat
and modified by Duckett, which describes the location of the meatus after correction of any associated
chordee.
[2, 3]
Descriptive locations include anterior (glanular and subcoronal), middle (distal penile,
midshaft, and proximal penile), and 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 is shown. Note the deficient ventral foreskin, blind urethral pit at the
glanular level, and lighter pigmented urethral plate extending to the true meatus at the proximal shaft level.
Proximal shaft hypospadias is shown. Note the typical dorsal hood of foreskin and
ventral penile skin deficiency. Penoscrotal hypospadias is shown. Note the associated ventral
chordee and true urethral meatus located at the scrotal level.
Physical
Although the diagnosis of hypospadias has been made using both prenatal fetal ultrasonography and
MRI, the diagnosis is generally made upon examination of the newborn infant.
[5]

A dorsal hood of foreskin and glanular groove are evident, but, upon closer inspection, the prepuce is
incomplete ventrally and the urethral meatus is noted in a proximally ectopic position. Rarely, the
foreskin may be complete, and the hypospadias is revealed at the time of circumcision. If hypospadias
is encountered during neonatal circumcision, after the dorsal slit has been performed, the procedure
should be halted, and the patient should be referred for urologic evaluation.
Chordee may be readily apparent or discernible only during erection. Proximal hypospadias is
commonly associated with a bifid scrotum and penoscrotal transposition, in which the rugated scrotal
skin begins lateral to the penis rather than in its normal posterior origin.
See the image below. Penoscrotal transposition is shown. Note the rugated scrotal skin
lateral to the penis, cephalad to its normal position.
Causes
Several etiologies for hypospadias have been suggested, including genetic, endocrine, and
environmental factors.
Genetic factors
o A genetic predisposition has been suggested by the 8-fold increase in incidence of hypospadias
among monozygotic twins compared with singletons. This finding may relate to the demand of 2
fetuses for human chorionic gonadotropin (HCG) produced by a single placenta, with an inadequate
supply during critical periods of urethral development.
o 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
o 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 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.
o 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.
o A 5-fold increased risk of hypospadias appears to exist in males born through IVF when compared
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.
o Other factors that contribute to infertility, such as underlying endocrinopathies or fetal endocrine
abnormalities, may play a role.
Environmental factors
o Endocrine disruption by environmental agents is gaining popularity as a possible etiology for
hypospadias and as an explanation for its increasing incidence.
o 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, from plastic linings in metal cans, and in pharmaceuticals.
o A study by Hadziselimovic in 2000 described an increase in estradiol concentration in placental basal
syncytiotrophoblasts of boys withundescended testes compared with a control
population.
[8]
Undescended testes and hypospadias have been associated, but increased estradiol
concentration has not been implicated in hypospadias per se. This may support the association of
hypospadias with increasing parity, increasing maternal age, and low birth weight noted in some
studies in relation to lifelong exposure to environmental disruptors and a possible cumulative effect.
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]

Differential Diagnoses
Ambiguous Genitalia and Intersexuality
Circumcision
Genital Anomalies
Imaging Studies
Upper urinary tract anomalies are rarely associated with hypospadias and do not justify routine
imaging in these patients unless other organ system anomalies are present. Other associated
findings are more common (eg, enlarged prostatic utricle, low-grade vesicoureteral reflux) but are
of little consequence clinically unless other symptoms merit evaluation.
[12]

Surgical Care
The goals of treating hypospadias are to create a straight penis by repairing any curvature
(orthoplasty), to create a urethra with its meatus at the tip of the penis (urethroplasty), to re-form
the glans into a more natural conical configuration (glansplasty), to achieve cosmetically
acceptable penile skin coverage, and to create a normal-appearing scrotum. The resulting penis
should be suitable for future sexual intercourse, should enable the patient to void while standing,
and should present an acceptable cosmetic appearance.
Timing of surgery
Before 1980, hypospadias repair was performed in children older than 3 years because of the
larger size of the phallus and a technically easier procedure; however, genital surgery at this age
(genital awareness occurs at about age 18 mo) can be associated with significant psychological
morbidity, including abnormal behavior, guilt, and gender identity confusion.
Currently, most physicians attempt to repair hypospadias when the child is aged 4-18 months,
trending toward earlier intervention. This has been associated with an improved emotional and
psychologic result. A benefit in wound healing with earlier repair has also been perceived and
may have a basis in the reduced proinflammatory cytokine production noted at younger age.
[13]

Late hypospadias repair, in the pubertal and postpubertal period, is associated with
complications, primarily urethrocutaneous fistula, in nearly half of patients. More recent reports
suggest a higher rate of complication in 5-year-old patients than in 1-year-old patients, suggesting
that earlier repair is generally better.
[14]

Types of repair
The specific techniques for hypospadias repair are beyond the scope of this article
(see Urogenital Reconstruction, Penile Hypospadias); however, the types of repairs can be
generically grouped, and the approach to the repair is relatively standard.
After fully assessing the penile anatomy, the shaft skin of the penis is degloved to eliminate any
skin tethering, and an artificial erection is performed to rule out any curvature. Mild-to-moderate
chordee may be repaired by excising any ventral fibrous tethering tissue or by plicating the dorsal
tunics of the corporal bodies, compensating for any ventral-to-dorsal disproportion. More severe
chordee may require grafting of the ventral corporal bodies using synthetic, animal (small
intestinal subunit), cadaveric, or autologous tissues (tunica vaginalis or dermal grafts) to avoid
excessive shortening of penile length. On rare occasion, the urethral plate may be tethered and
transection of the plate may be required, precluding the use of native urethral tissues for
urethroplasty.
The urethra may be extended using various techniques. These techniques are generally
categorized as primary tubularizations, local pedicled skin flaps, tissue grafting techniques, or
meatal advancement procedures.
The tubularized incised plate (TIP) repair has become the most commonly used repair for both
distal and midshaft hypospadias. This technique is a primary tubularization of the urethral plate,
with incision of the posterior wall of the plate, which allows it to hinge forward (see the image
below). This creates a greater diameter lumen than would otherwise be possible, obviating the
routine use of a flap or graft to bridge a short narrow segment of urethral plate. The procedure
has proved adaptable to various settings, and current surveys indicate that this is the procedure
of choice for most repairs by most urologists.
Various sutures have been used in the repair of hypospadias, but polyglycolic acid based
sutures may offer the best balance of resilience when exposed to urine, without excessive time to
absorption resulting in a foreign body reaction.
[15]
See the image below.
Tubularized incised plate (TIP) technique. The urethral plate has been incised in the
dorsal midline, expanding the width of the plate and allowing it to hinge forward for tubularization.
The general concept that increasing the layers of tissue between the urethra and overlying skin
coverage result in a lower likelihood of the later development of urethrocutaneous fistula has
been supported by recent studies.
[16]
Temporary urethral stents are a common adjunct to
hypospadias repair and are felt to decrease the likelihood of fistula formation. Various different
drainage tubes have been utilized for this purpose.
[17]
To stent or not to stent is an ongoing
controversy, balancing the risk of irritative symptoms and urinary tract infection with the risk of
urinary retention.
[18]

For repeat repairs after unsuccessful surgery for hypospadias when local tissues are unavailable,
buccal mucosa has been used for urethral grafting. This tissue is well suited for this purpose
because of its availability, characteristics that favor graft success, and its resilience to a moist
environment. Urethral stents are generally used for bladder drainage while healing occurs in all
but the most distal hypospadias repairs.
Steps of repair
Glans flaps are generally mobilized to cover the distal urethral repair, bringing the divergent
ventral components to the midline and creating a more conical configuration. The excess dorsal
skin is mobilized to the deficient ventral aspect of the penis for final skin coverage.
The repair of penoscrotal transposition is often performed as a staged procedure because the
necessary incisions may compromise the vascular pedicle to skin flaps used in the primary
urethroplasty. The repair of penoscrotal transposition is usually deferred at least 6 months to
allow for adequate formation of collateral blood supply.
The repair of hypospadias is generally planned as a single-stage procedure, but excessive
chordee (especially if transection of the urethral plate is required), poor skin availability, and small
phallic size may be better approached in a staged manner. The chordee is repaired and the skin
is mobilized to the ventral penile shaft during the first stage, and the urethroplasty and glansplasty
are repaired after the first stage has completely healed.
Adjuvant hormonal therapy
Although no medical therapy for the correction of hypospadias is known, hormonal therapy has
been used as an adjuvant treatment for infants with exceptionally small phallic size. Presurgical
treatment with testosterone injections or creams, as well as HCG injections, has been used to
promote penile growth, and some have reported improvement in chordee with lessening in the
severity of the hypospadias. The fact that prepubertal androgen therapy may limit normal genital
growth at puberty is a concern but has not been confirmed clinically
Complications
It is clear that repairs that are more proximal are associated with a greater incidence of
complications. Older age at surgery and low surgical experience have also been associated with
poorer outcomes. With longer follow-up, it is apparent that late complications can occur and most
advocate continued evaluation through puberty.
[19, 20, 21, 22]

Immediate postoperative concerns
Local edema and blood spotting can be expected early after repair and generally do not cause a
significant problem.
Postoperative bleeding rarely occurs and is usually controlled with a compressive dressing.
Infrequently, this requires reexploration to evacuate a hematoma and to identify and treat the
source of bleeding.
Infection is a rare complication of hypospadias repair in the modern era. Skin preparation and
perioperative antibiotics are generally used. Patients are often maintained on an antibiotic course
until any stents are removed, although this has not clearly been shown to be of benefit.
[23]

Long-term issues
Urethrocutaneous fistulization is a major concern in hypospadias repair. The rate of fistula
formation is generally less than 10% for most single-stage repairs but rises with the severity of
hypospadias, approaching 40% with complex reoperative efforts. Fistulas rarely close
spontaneously and are repaired using a multilayered closure with local skin flaps 6 months after
the initial repair. After repair, fistulas recur in approximately 10% of patients. See the image
below.
A urethrocutaneous fistula has appeared after hypospadias repair. Note one
stream from true urethral meatus, and second stream through more proximal fistula.
Meatal stenosis, or narrowing of the urethral meatus, can occur. A urethral stent prevents any
problems initially, but a fine-spraying urinary stream that is associated with straining to void likely
requires operative meatal revision.
Urethral strictures may develop as a long-term complication of hypospadias repair. These are
generally repaired operatively and may require incision, excision with reanastomosis, or patching
with a graft or pedicled skin flap.
Urethral diverticula may also form and are evidenced by ballooning of the urethra while voiding. A
distal stricture may cause outflow obstruction and may result in a urethral diverticulum. Diverticula
can form in the absence of distal obstruction and are generally associated with graft- or flap-type
hypospadias repairs, which lack the subcutaneous and muscular support of native urethral tissue.
The redundant urethral tissue is generally excised, and the urethra is tapered to an appropriate
caliber.
Hair-bearing skin is avoided in hypospadias reconstruction but was used in the past. When
incorporated into the urethra, it may be problematic and can result inurinary tract infection or
stone formation at the time of puberty. This generally requires cystoscopic depilation using a laser
or cautery device or, if severe, excision of hair-bearing skin and repeat hypospadias repair.
Newer surveys have suggested milder forms of erectile dysfunction may be more common with
more proximal hypospadias repairs.
[24