Pathophysiology

Hypospadias is a congenital defect that is thought to occur during the embryologic

Hypospadias  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
Updated: Aug 23, 2021 influence of testosterone and its byproduct, dihydrotestosterone. As the phallus
Author: John Michael Gatti, MD; Chief Editor: Marc Cendron, MD  grows, the open urethral groove extends from its base to the level of the corona.

Overview
Practice Essentials
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 may be splayed open.[1] In more
severe forms, the urethral opening may be located as proximal as in the scrotum or
perineum. The penis may present with associated ventral shortening and curvature,
called chordee, with more proximal urethral defects.
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.

Galen, in the second century CE, may be credited with the earliest medical text to
The prepuce normally forms as a ridge of skin from the corona that grows
use the term hypospadias. During the first millennium, the primary treatment for
circumferentially, fusing with the glans. Failure of fusion of the urethral folds in
hypospadias was amputation of the penis distal to the meatus. Since that time,
hypospadias impedes this process, and a dorsal hooded prepuce results. On rare
surgical repair has progressed in relation to advances in surgical instruments,
occasions, a glanular cleft with intact prepuce may occur, which is termed the
introduction of anesthesia, and innovation in suture material. Stretching the urethra
megameatus intact prepuce (MIP) variant.
gave way to tunneling procedures and, ultimately, to flaps and tubularization in the
modern era.[2]
Ventral curvature of the penis, termed chordee, is often associated with
hypospadias, especially in more severe forms. This is thought to result from a
Many have contributed to development of modern hypospadias repair. More than
growth disparity between the normal dorsal tissue of the corporal bodies and the
400 different types of repairs have been described in the medical literature.
attenuated ventral urethra and associated tissues. The abortive spongiosal tissue
Although most reports have been in the past 60 years, most basic techniques were
and fascia distal to the urethral meatus may form a tethering fibrous band that
described more than a century ago.[2]
contributes to the ventral curvature. This can range from mild to very severe (90º
angle). (See the image below.)
Modern anesthetic techniques, fine instrumentation, sutures, dressing materials, Severe penile chordee. Note extreme ventral curvature of penile shaft.
and antibiotics have improved clinical outcomes and have, in most cases of less
severe hypospadias, allowed surgical treatment with a single-stage repair within the
first year of life on an outpatient basis. 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 described 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.)
Glanular (balanic) hypospadias with "figure-eight" meatus. Dorsal pit is blind
ending; ventral opening is actual urethral meatus.
Megameatus intact prepuce (MIP) variant of hypospadias.
Megameatus intact prepuce (MIP) variant of hypospadias, apparent once
foreskin is retracted.
Subcoronal hypospadias. Note distal blind-ending false pit at level of glans.
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 hood of foreskin and ventral
penile skin deficiency.
Penoscrotal hypospadias. Note associated ventral chordee and true urethral
meatus located at scrotal level.
Etiology
Several etiologies for hypospadias have been suggested, including genetic,
endocrine, and environmental factors.
Genetic factors
A genetic predisposition has been suggested by a fourfold increase in the 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.[6]
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.[7]
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.[8]
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.[9]  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 threefold increased risk of hypospadias appears to exist in males born through
assisted reproductive techniques. This may reflect maternal exposure to
progesterone, which is commonly administered in in-vitro fertilization (IVF)
protocols. Progesterone is a substrate for 5-alpha reductase and acts as a
competitive inhibitor of the T-to-DHT conversion. Other theories have suggested
that an inherited testosterone deficit may be causal.[10, 11]
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.[12]
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.[13, 14]
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.[15, 16]
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.[17, 18]
Race-related demographics
Historically, the incidence of hypospadias was reported to be higher in whites than
in Blacks, and more common in those of Jewish and Italian descent. Subsequent
assessment revealed a more balanced incidence among different race groups.[19]
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 have been limited. 
Although some earlier studies were discouraging, these reflected 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.
Hypospadias surgical complications have been described in the single digits for
distal repair; however, longer follow-up, greater standardization in assessment and
outcome parameters, and possibly more honest reporting have revealed
complication rates approaching 50% for more proximal defects. This has given rise
to renewed enthusiasm for a staged approach to these more complex forms of
hypospadias, given the higher rates of success despite a second operation.[20]
Newer scoring systems designed to lend objective measures to long-term outcomes
are becoming more popular.[21]  The HOPE score is a physician-assigned score
shown to correlate with the severity of hypospadias; higher HOPE scores (milder
hypospadias) were associated with less need for repeated operative interventions.
[22, 23]
A more recent focus has been the recurrence of penile curvature after initial
correction. One study found that more than 80% of those undergoing reoperation for
hypospadias complications had some component of residual or recurrent curvature.
These recurrences were more common after chordee excision or plication repairs
than after corporal lengthening procedures.[24]
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.[25]
The literature has been expanding tremendously with regard to the assessment of
the perception of success. In a Canadian study, more than half of the patients or
parents of patients undergoing treatment of mild hypospadias had no decisional
regret; however, many (40%) experienced mild regret, and a significant number
(6%) experienced moderate-to-severe regret.[26] There was significant association
with the desire to avoid circumcision and a high initial decisional conflict level.
Similar findings were noted in the United Kingdom, where regret was primarily
associated with a small glans size, distal meatal location (mild hypospadias), and
complications necessitating reoperation.[27] In this study, the level of regret was
similar between those who were circumcised and those were not. This did not
appear to be associated with the surgeon's experience.
Although the techniques of hypospadias repair continue to evolve, the broader
future of hypospadias treatment is encouraging. Nontraditional tissue adherence
techniques have been developed, including tissue glues and laser-activated
soldering techniques, but have not been widely adopted.
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.
Patient Education
Because most patients with hypospadias are surgically treated at a very young age,
parental teaching and reassurance are very important for ensuring a satisfactory
experience for the families of these patients. Early consultation with a pediatric
urologist may help parents to understand the issue better, have realistic
expectations, remove guilt, and provide a management plan.[28] Evidence suggests
that online support groups can play an important role in how parents and patients
cope with hypospadias.[29]
Presentation
History
Obtain a thorough history and physical examination, including any history of a
familial pattern of hypospadias, any past medical history or comorbidity, and a
physical assessment focusing on the meatal location, glans configuration, skin
coverage, and ventral curvature (chordee).
A history of parental difficulties in conceiving and treatment should also be
documented; in-vitro fertilization (IVF) has been associated with a higher incidence
of hypospadias.
Physical Examination
Although the appearance of hypospadias has been identified with both antenatal
fetal ultrasonography (US) and magnetic resonance imaging (MRI), the diagnosis is
generally made upon examination of the newborn infant.[30]
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
an abnormal proximal location. 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.
Penile curvature may be readily apparent or may be discernible only during
erection. Proximal hypospadias is commonly associated with a bifid scrotum and
penoscrotal transposition (see the image below), in which the rugated scrotal skin
begins lateral to the penis rather than in its normal posterior origin.
Penoscrotal transposition. Note rugated scrotal skin lateral to penis, cephalad to
its normal position.
DDx
Diagnostic Considerations
In 1981, a review by Khuri of more than 1000 patients with hypospadias reported
that the incidence of undescended testes and inguinal hernias was 9% for each.[31]
With more severe forms of hypospadias, the incidence of undescended testes
exceeded 30%, and the incidence of inguinal hernias approached 20%. It is
important to evaluate the position of the testes and assess for the presence of
inguinal hernia as part of the physical examination for hypospadias.
The combination of hypospadias and undescended testis can be an indicator of an
underlying difference/disorder of sex development (DSD).[32] In a 1999 study by
Kaefer et al, DSD states were identified in approximately 30% of patients with
unilateral or bilateral undescended testes and hypospadias, and more proximal
meatal location carried a higher association of DSD states than more distal meatal
location.[33] If any gonad was nonpalpable, the incidence rose to 50%; however, if
both gonads were palpable, the incidence was only 15%.
A prostatic utricle is occasionally noted when catheterization of the urethra is
attempted in patients with hypospadias. A prostatic utricle is a müllerian duct
remnant that typically regresses in boys. There is a high association between a
prominent utricle, an outpouching off the posterior aspect of the prostate, and
hypospadias, particularly the more severe forms. These are often asymptomatic but
can cause difficulty with catheterization, lead to stasis of urine and urinary tract
infection, or collect debris or stones. They sometimes require surgical excision.[34]
Differential Diagnoses
 Circumcision
 Differences (Disorders) of Sex Development (DSDs)
 Genital Anomalies
Workup
Workup
Laboratory Studies
No laboratory tests have been found to be helpful in the evaluation and
management of hypospadias. In cases where a disorder/difference of sex
development (DSD) is suspected, hormonal evaluation may be needed.
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 [VUR]) but are of little consequence clinically unless
other symptoms merit evaluation.[35]
It has been argued that prostatic utricles are an underappreciated cause of urologic
morbidity and may present as penile pain with voiding, hematuria, epididymitis, and
urinary tract infection (UTI) and therefore should be sought with retrograde
urethrography in the setting of proximal hypospadias.[36]
Procedures
In very rare instances, presence of meatal stenosis may prevent normal egress of
urine and cause distal ballooning of the urethra. This may necessitate a temporizing
meatoplasty to allow normal flow of urine.
Treatment
Approach Considerations
The treatment for hypospadias is surgical repair. Repair is generally performed for
functional and cosmetic reasons. The more proximally ectopic the position of the
urethral meatus, the more likely the urinary stream is to be deflected downward,
which may necessitate urination in a seated position. Any element of ventral
curvature (chordee) can further deflect the urinary stream. The abnormal deflection
of ejaculate may preclude effective insemination, and significant chordee can
preclude vaginal insertion of the penis or can be associated with inherently painful
erections.
Minor cases of hypospadias, in which the meatus is located distal to the corona on
the glans, may not require surgical repair and may simply be managed with
observation. It must be kept in mind, however, that although the most minor forms
of hypospadias are insignificant in physiologic terms, they too may merit repair on
the basis of the potential long-term psychological stress associated with having
abnormal genitalia.
Surgical Care
The goals of surgical treatment of hypospadias are as follows:
 To create a straight penis by repairing any curvature (orthoplasty)
 To create a urethra that opens at the tip of the penis (urethroplasty) with a
natural slitlike configuration (meatus)
 To re-form the glans into a more natural conical configuration (glansplasty)
 To achieve cosmetically acceptable penile skin coverage
 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. As the
technical aspects of hypospadias surgery progressed, the size of the phallus was
no longer the limiting factor in the ideal timing of repair.
The 1996 statement by the Section on Urology of the American Academy of
Pediatrics (AAP) recommended the ideal timing of repair as 6-12 months of age on
the basis of anesthetic safety, genital awareness in the child and minimization of
psychological morbidity, abnormal behavior, and gender identity confusion.[37]  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 ages.
[38]  More recent concerns regarding early exposure to general anesthesia has
reinvigorated this topic (see below).
Late hypospadias repair, in the pubertal and postpubertal period, is associated with
complications, primarily urethrocutaneous fistula, in nearly 50% of patients.[39]
Some reports cited a higher rate of complications in 5-year-old patients than in 1-
year-old patients, suggesting that earlier repair is generally better.[40] Others also
reported high rates of complications in adults.[41]  Subsequent reports, however,
cited comparable complication rates across age groups.[42]
Some argue that hypospadias should not be repaired until the child is able to
consent to the procedure himself. This position represents a dramatic shift from
what has been the standard of care for decades. It must be remembered that
deferring repair until the teenage years is, at this point, an unproven approach, in
that there is no large scientific cohort literature assessing the psychological and
social impact of withholding genital reconstruction in this population.[43, 44]
An electronic survey using Facebook identified 52 adult men with untreated
hypospadias and reported worse outcomes for these men than for nonhypospadiac
men.[45] Those with severe hypospadias had more adverse outcomes. Outcome
measures included lower sexual health scores, worse prostatic symptom scores,
more ventral penile curvature and resulting difficulty with intercourse, worse
satisfaction with meatus and penile curvature, and more sitting to urinate.
In 2016, the United States Food and Drug Administration (FDA) released a Drug
Safety Communication warning stating that repeated or lengthy use of general
anesthetic or sedative drugs during operations or procedures in children younger
than 3 years of age or in pregnant women during the final trimester may affect
development of children's brains. Lengthy, in this context, was defined as longer
than 3 hours. The FDA recommended that caution be exercised regarding the
possible risks of delaying needed surgical or diagnostic procedures and that parents
and providers carefully weigh the risks and benefits of each procedure until more
information is available.
Since then, several efforts have been made to evaluate this risk objectively. One
sibling-matched cohort study found no significant differences in IQ scores in later
childhood between healthy children with a single anesthesia exposure before the
age of 36 months and healthy siblings with no anesthesia exposure.[46]  
As of 2019, the GAS study, an international prospective randomized controlled
study, had shown no cognitive differences between patients undergoing general
anesthesia in infancy for inguinal hernia repair (an operation similar in duration to
hypospadias surgery), and those using only regional anesthesia at 2 and 5 years of
age.[47, 48]
A 2021 article by Sepulveda et al noted that such studies typically did not
differentiate between the drug administration techniques employed (inhaled or
intravenous) or specify whether electroencephalographic (EEG) brain monitoring
was performed.[49]  
Evidence will continue to accrue, but the good-quality evidence amassed to date
suggests that limited general anesthesia in infancy is safe.
These issues are important for consideration and should be included in the
discussion with families before any surgical reconstruction.
Types of repair
The specific techniques for hypospadias repair are beyond the scope of this article
(see Penile Hypospadias Reconstruction); however, the types of repairs can be
generically grouped, and the approach to the repair is relatively standard.
The urethra may be extended by using various techniques. These techniques are
generally categorized as follows:
 Primary tubularizations
 Local pedicled skin flaps
 Tissue-grafting techniques
 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. This creates a lumen of greater diameter than
would otherwise be possible, obviating the routine use of a flap or graft to bridge a
short narrow segment of urethral plate. (See the images below.)
Tubularized incised plate (TIP) technique. Urethral plate has been isolated
(dissected) prior to midline incision. Note starting position of urethral opening at
base. Assistance with image editing provided by Joseph Borer, MD.
Tubularized incised plate (TIP) technique. Urethral plate has been incised to
allow expansion for tubularization. Note deep midline incision (cut edges
marked in blue) and widening of urethral plate. Assistance with image editing
provided by Joseph Borer, MD.
Tubularized incised plate (TIP) technique. Incised plate has been tubularized
over 8-French tube. Note final position of urethral opening at tip of penis, and
note that meatus is left quite wide. Assistance with image editing provided by
Joseph Borer, MD.
The TIP repair has proved adaptable to various settings, and current surveys
indicate that it is the procedure of choice for most repairs by most
urologists. Although it is favored by many, if the urethral plate is contributing to
curvature, transection of the urethral plate to correct curvature will preclude the use
of the TIP technique for complete urethral reconstruction.
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.[50]
Studies support the general concept that increasing the layers of tissue between the
urethra and overlying skin coverage makes subsequent development of
urethrocutaneous fistula less likely.[51] Temporary urethral stents are a common
adjunct to hypospadias repair and are felt to decrease the likelihood of fistula
formation. Various drainage tubes have been utilized for this purpose.[52] 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.[53]
In a retrospective-prospective observational study of 189 patients that compared 1
week of transurethral bladder catheterization after hypospadias repair with 3 weeks
of catheterization, Daher et al found the longer catheterization period to be
associated with better outcomes and fewer complications.[54] A subsequent meta-
analysis found that duration and presence of catheter drainage may have little affect
on outcome.[55]
In the setting of repeat repair 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 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
Hypospadias repair includes many steps. The penis is degloved of skin to eliminate
any component of skin tethering to curvature. Commonly, an erection is induced
pharmacologically or by instillation of saline solution into the corporal tissues; this
allows objective assessment of curvature.[56, 57]  The ideal method for the
objective assessment of the degree of penile curvature has become a controversy.
Many have advocated measuring angulation with a goniometer, but more recent
proposals have invovled a mobile application to correlate a photograph with defined
degrees of angulation. Studies not shown any particular method to be superior to a
subjective estimate or the so-called eye test.[58, 59]
Straightening of the penis (orthoplasty) is accomplished by removing any ventral
tissue that limits the expansion of the corporal bodies. If this is not sufficient, milder
chordee (commonly considered < 30º) can be corrected further through dorsal
plication of the corporal bodies, generally in the midline to avoid injury to the nerves
of the penis that course on the lateral aspect of the dorsum. This compensates for
any dorsal-to-ventral corporal disproportion.
For greater degrees of chordee in which the urethral plate itself contributes to
ventral curvature, the urethral plate is transected and dissected off the corporal
bodies; this ultimately requires intervening urethral replacement and a staged
approach. For persistent curvature, horizontal relaxing incisions in the corporal
bodies, with or without grafting, may be required to straighten the penis further. A
popular approach is to use the STAG (straighten and graft) or the STAC (straighten
and cover) technique, in which the ventral corpora are deeply and transversely
incised in tandem at the point of maximal curvature.
If the urethral plate can then be used to cover the corporotomy sites, the remaining
defect is grafted, typically with prepuce or buccal mucosa (STAG technique). If the
corporotomies cannot be covered with native urethral tissue, they are covered with
adjacent hair-bearing skin, and the segment between urethral segments is
grafted later (STAC technique). In the past, great efforts were made to cover these
corporotomies with tissue such as dermis or synthetic material, but this approach
has largely fallen out of favor.
It is essential to carry out an artificial erection test after attempts to correct curvature
to assess the results of the procedure and ensure that the penis has been
adequately straightened.[60]
If the penis is straight initially, several different approaches to creation of a tubular
urethra with its opening at the tip of the glans may be undertaken. These involve
tubularization or adjacent skin flap techniques. A narrow strip of urethral plate can
still be reconstructed by incising the plate in the midline to allow it to expand and
hinge ventrally for tubularization around a stent or catheter (the TIP technique). This
latter technique also works well for repair when the penis has been straightened
without transection of the urethral plate.
Repair of the glans (glansplasty) is accomplished by mobilizing the tissues ventrally
to allow the edges to approximate in the midline over the tubularized urethra.
Finally, the skin is tailored and the penile shaft resurfaced. Skin deficits may be
treated with local skin flap coverage from the scrotum or with tissue grafting.
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
severe ventral penile curvature, poor skin availability, and small phallic size may be
better approached in a staged manner, as described above. Generally, the
curvature is corrected and tissue for later urethral reconstruction is relocated to the
ventral penile shaft during the first stage; the urethroplasty and glansplasty are
performed after the first stage has completely healed, usually at least 6 months
later.
Adjuvant hormonal therapy
Although no corrective medical therapy for hypospadias is known, hormonal therapy
has been used as an adjuvant to surgical therapy in infants with exceptionally small
phallic size. Preoperative treatment with testosterone or human chorionic
gonadotropin (HCG) injection has been used to promote penile growth; some have
reported improvement in chordee with lessening in the severity of hypospadias.
That prepubertal androgen therapy may limit normal genital growth at puberty is a
concern, but this has not been confirmed clinically. Hormonal creams are typically
avoided because of variable transcutaneous absorption.
One group reported preoperative parenteral testosterone administration to be
beneficial in decreasing complication rates (from 13.18% to 5.45%).[61] Others,
however, have reported increased postoperative complications (including fistula and
dehiscence) when testosterone is used, findings that have tempered enthusiasm for
this measure.[62]  A retrospective study with longer-term follow-up (18 years)
suggested that the outcomes of cosmesis, penile length, body height, and
complications were similar with and without testosterone supplementation.[63]
Complications
It is clear that repairs that are more proximal are associated with a greater incidence
of complications.[64, 65] Older age at surgery and low surgical experience have
also been associated with poorer outcomes. A study from England by Wilkinson et
al found that staged repairs were associated with higher complication rates and that
high-volume centers had lower complication rates.[66]
With longer follow-up, it is apparent that late complications can occur, and thus,
most advocate continued evaluation through puberty.[67, 68, 69, 70]  A long-term
analysis by Nguyen et al showed that the incidence of secondary surgical repair of
hypospadias is underreported if follow-up is limited to less than 6 years.[71]
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, reexploration may be required 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, though this has not
clearly been shown to be beneficial.[72]
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 by 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.)
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 may necessitate evaluation and possible surgical revision of
the distal urethra.

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 in urinary
tract infection (UTI) 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.

Some surveys have suggested that milder forms of erectile dysfunction may be
more common with more proximal hypospadias repairs.[73]