Introduction

Hypospadias is one of the most common congenital anomalies with an estimated prevalence of 65 cases per 10,000 male live births in the USA [1]. Hypospadias is characterized by proximal dislocation of the urethral meatus along the ventral aspect of the penis, an incompletely formed ventral prepuce, and chordee. Hypospadias has a spectrum of severity, classified by position of the urethral opening prior to any manipulation. The majority of cases have a mild phenotype with the urethral meatus located at the distal penile shaft or glans. However, approximately one-third of cases are more complex with a more proximally positioned meatus, potentially requiring multi-stage surgical correction. These cases also have a higher incidence of associated congenital anomalies including undescended testicles and disorders of sexual development, adding complexity to the surgical treatment course [2, 3].

Surgical correction is typically performed between 6 and 18 months of life and can be a one or multi-staged procedure depending on phenotypic complexity [4]. The principal aims of hypospadias repair includes repositioning of the urethral opening near a more orthotopic glans position, creation of a straight phallus with the goal of providing an improved urinary and sexual function as well as acceptable cosmetic appearance. There is vast literature reporting favorable short and intermediate hypospadias repair outcomes regarding function and cosmetic appearance, with the most successful outcomes reported in patients with a more distal phenotype [5, 6].

Most pediatric hypospadias patients are discharged from urologic care before puberty. However, a fraction of patients with surgically treated hypospadias may fail, requiring long-term management and repeat procedures by adult reconstructive urologists. Even for those patients deemed an anatomical success, some clinical consequences from hypospadias and subsequent repair including cosmesis and sexual function may not emerge as a concern until early adulthood. In fact, the prevalence of hypospadias complications in adulthood remains unknown. This makes it challenging for pediatric urologists to appropriately counsel families of the risk of post-pubertal complications. Here, we review the prognosis and functional outcomes of the hypospadias population in adulthood. A summary of all current studies reviewed in this article with a focus on erectile dysfunction, fertility, and psychosexual outcomes is presented in Table 1.

Table 1 Summary of current studies reviewed
Full size table

Overall Outcomes

In the pediatric literature, distal hypospadias repair success is high, ranging from 85 to 94% [7, 8]. Complication rates are considerably higher in proximal hypospadias patients ranging from 30 to 68%, attributable to an increased severity phenotype and procedural complexity [9,10,11]. In the past few years, there has been an increased recognition of a higher complication rate and potential delay in complication presentation, particularly for patients with proximal phenotypes. Many of these men can have delayed development of urinary complications presenting decades after initial repair. While males with history of hypospadias repair account for 9–12% of anterior urethral stricture cases, the rate of delayed complications in adult patients with history of hypospadias repair is not well established [12,13,14]. This can be attributable to an overall lack of studies evaluating longitudinal outcomes, limited access to transitional urologists, the inability to quantify patients without delayed complications, and potentially decades-long interval to complication presentation.

The most common delayed hypospadias complications presenting in adulthood include urethral stricture disease (25–72%) and urethrocutaneous fistula (24–32%) [15•, 16•]. Complications reported less commonly include persistent hypospadias, persistent ventral curvature, and/or glans deformity. A prior report comprising the largest cohort of adult males with hypospadias complications identified that most patients with complications in adulthood had multiple operations as part of a primary repair with 19% of men with a staggering history of four of more prior reconstructive surgeries [15•]. Twenty-three percent of patients had initial meatal position at the penoscrotal junction [15•]. This highlights the complexity and variability of patients presenting with complications, suggesting the importance of post-pubertal urologic follow-up in complex hypospadias repair cases. In less complex cases and/or patients deemed successful with more distal repairs, patients and their families should be counseled on the importance of seeking evaluation should voiding difficulty arise.

The complexity of these patients is further underscored by the modest success rates of first attempted repair of delayed hypospadias complications in adulthood. Myers and colleagues reviewed outcomes of adult men with a history of hypospadias repair presenting with delayed complications and reported an initial success rate of 50% (25/50) [16•]. Of these patients considered to be a failure of repair, 69% (18/25) required repeat intervention to both correct complication and achieve desired surgical outcome [16•]. The most common complication related to repair in adulthood includes urethral strictures (46%) and urethrocutaneous fistula formation (42%) [16•]. However, when considering repeat repair attempts, the overall success rate increased to 76% in this single center study [16•]. When evaluating success of urethral stricture repair, stage one urethroplasty had the highest overall success at 88%, compared to one-stage and two-stage urethroplasty at 72% and 73%, respectively [16•]. In the patients in whom therapy ultimately failed, 4 patients had persistent urethrocutaneous fistulas, and 5 patients had urethral narrowing requiring repeat dilation or intermittent catheterization for adequate patency [16•].

Repair Strategies of Hypospadias Stricture and Related Recurrences

Adult patients presenting with delayed urethral stricture disease have added anatomical complexity due to hypovascularity, poor tissue quality and quantity often warranting urethral substitution and repeat staging. As such, a considerable proportion of these patients may warrant multiple surgeries to achieve a satisfactory outcome. Similar to the initial hypospadias repair in the pediatric setting, there is no operative approach that fits-all and often requires multiple, ancillary reconstructive surgical techniques to achieve a successful surgical outcome. The type of urethroplasty performed is determined by multiple anatomical considerations including width of the glans and urethral plate, scarring of the urethral plate, chordee severity, location of stricture, and availability of ventral skin for coverage.

Even prior to initial repair, patients with hypospadias have impaired blood supply, specifically deficient retrograde flow from terminal branches of the dorsal arteries due to absence of normal corporal spongiosum [17]. This is particularly the case for patients with severe phenotypes and history of multiple prior repairs, placing these patients at added risk of future complications, notably recurrent urethral strictures. Preservation of proximal blood supply is compulsory in these patients and is primarily why excisional and primary anastomosis (EPA) is not commonly utilized in this patient population. Excisional and primary anastomosis is reliant on retrograde flow, as this operative approach involves full transection of the urethra and surrounding spongiosum containing antegrade flow from bulbar arteries. If the anatomy is amenable, there is often an attempt made to perform unilateral urethral dissection of the underlying corpora cavernosa to preserve the contralateral blood supply [18]. However, this dissection technique is not always able to be performed due to significant scarring.

Single-stage dorsal inlay urethroplasty is a suitable option in select patients with hypospadias surgery-related strictures in the bulbar and/or penile location [19, 20, 21•]. Patients must be selected carefully based on intraoperative assessment as they must have acceptable urethral plate width/quality, adequate tissue mobility, and glans width for a tension-free closure. For more distal strictures, a ventral urethral incision is utilized. For more proximal strictures involving the bulbar and/or penile urethra, a midline perineal incision is made followed by dissection. A urethral incision is made in a dorsal or lateral fashion at the level of the stricture and extended 1 cm beyond the strictured segments at both ends [21•]. The pre-harvested graft is fixed over the exposed area of corpora. Other methods of graft placement including ventral onlay is avoided as these patients do not have sufficient nutritional or mechanical support for ventral graft placement. The urethra is then tubularized followed by closure of incision in a minimum of two layers to decrease risk of fistula formation.

Many adults presenting with urethral stricture following childhood hypospadias repair have absent or a severely scarred urethral plate and surrounding spongiosum and will require a staged, circumferential reconstruction of the penile urethra. Reported rates of staged repair in the literature range from 35 to 58% [15•, 16•]. A staged approach is often preferred in men with hypospadias-related strictures, as the urethra is often not able to withstand further compromise to blood supply required for wide mobilization in single-staged repairs, thus placing these patients at significant risk for ischemic stenosis [22, 23]. In the first stage, the scarred urethral plate and surrounding spongiosum is removed. Tunica vaginalis or dartos is then mobilized and sutured onto corporal bodies, followed by fixation of a buccal graft in a quilted suture fashion. It is theorized that placement of the graft onto a tunica or dartos base aids both neovascularization and tubularization at time of second stage. After graft has matured in 3 to 6 months’ time, the graft edges are carefully mobilized, and urethra is then tubularized.

Graft contracture rates ranges from 3 to 39% in the literature, which can turn a planned two-stage procedure into a multi-staged repair due to need for graft revision [24, 25]. As a result, Joshi and associates developed a novel approach involving both graft placement and tubularization as part of the second stage procedure [25]. With this approach, a first stage Johanson is performed in which a ventral midline incision is performed from meatus to 2 cm proximal to the strictured region [25]. Penile skin edges are approximated to urethral plate edges. In the second stage, a deep midline longitudinal incision is made into the urethral plate and a graft is sutured in a quilted fashion [25]. The neourethra is tubularized and glansplasty is performed. No prior studies have compared this approach to traditional two-stage repair in hypospadias-related strictures but is theorized that by decreasing exposure of environmental elements to the graft may help to keep the graft supple and decrease risks of graft shortening.

There are several techniques to correct residual adult ventral curvature. Traditionally, a technique first demonstrated in adults and still used today for Peyronie’s reconstruction, 16-dot plication, can be performed on the dorsal aspect of the penis through a circumcising or dorsal longitudinal incision [26]. Some surgeons avoid this approach, however, due to risk of penile shortening. In patients with a shorter length phallus, multiple transverse ventral corporal incisions or ventral corporal grafting can be considered during the first surgery of a planned staged repair [27].

Due to the physical and psychological burden of surgeries and related complications, a subset of men may elect to undergo an alternative procedure in lieu of full functional and cosmetic restoration. In men with history of multiple repairs, the glans is often malformed and hypovascularized. To decrease risk of future stenosis, preoperative counseling can include discussion of creation of a subcoronal meatus in lieu of a glanular meatal location. Perineal urethrostomy is a valid option in this patient population as this may offer decreased risk of re-intervention compared to formal urethroplasty [28]. Quality of life assessment of patients with long segment anterior urethral strictures who underwent perineal urethrostomy reported improved urinary function and no detrimental effects to sexual function [28]. Similarly, not all men may elect to undergo a second stage urethroplasty closure. Literature reports up to 30% of men may forge second stage urethral closure [29]. A first stage hypospadias repair may align with a patient’s surgical goals including elimination of primary voiding dysfunction as well as decreased added risks of stenosis that can arise with staged closure [29].

Erectile Function

The assessment of erectile function (EF) in adults who previously have undergone hypospadias repair is challenging due to a multitude of contributing factors including initial severity of hypospadias, potential hormonal abnormalities associated with more severe phenotypes, as well as sexual inhibition and/or anxiety related to genital appearance and prior surgery. Also, adult patients included in studies evaluating sexual outcomes may have undergone older reconstructive techniques no longer utilized by pediatric urologists. Current literature showcases an unclear consensus on this outcome, as the data is mixed with respect to the effect of hypospadias repair on erectile function.

A Dutch study evaluated erectile function using International Index of Erectile Function (IIEF) in 91 adult men with history of prior hypospadias repair and found no significant difference in erectile function compared to age matched controls [30]. Two-thirds of the patients in this study had history of distal hypospadias, and all patients including those with more severe phenotypes underwent one-stage planned repair [30]. There was no correlation between severity of hypospadias and EF [30]. Vandendriessche and colleagues found similar results using IIEF as a measure for EF when comparing adolescent males with a history of hypospadias repair compared to controls [31]. However, they did not report details concerning hypospadias severity, number, or type of repair of patients included in this study [31].

Nevertheless, these results are not universal. Chertin and associates included 119 patients with history of hypospadias [32]. In this study, a small proportion of patients (14.2%) required ventral corporoplasty for chordee correction, whereas the remaining patients were straight following penile skin degloving (no mention of corporoplasty) [32]. There was a higher incidence of erectile dysfunction (ED) in patients with proximal hypospadias as compared to distal hypospadias (72% vs. 50%). [32]. In total, 13/16 patients were found to have mild ED using IIEF questionnaires for evaluation, 3/16 with moderate ED and none with severe ED [32].

Husmann evaluated potential etiology of erectile dysfunction in adult patients with history of multiple hypospadias repairs (≥3 prior surgeries) [33•]. Of 100 patients included in the study, one-third of patients were found to have moderate to severe ED with Sexual Health Inventory of Men (SHIM) questionnaire scores ≤16 [33•]. There was no association between ED and location of the urethral meatus prior to correction nor the number of penile surgeries [33•]. Dorsal plication is typically reserved for low grade ventral chordee, not resolved with penile degloving. It was theorized that dorsal plication could cause damage to the neurovascular bundle, but this would be avoided if performed at the 12 o’clock position, as this region should be absent of nerves. This concept is corroborated by this study, which found no association between erectile dysfunction and a history of dorsal corporoplasty (dorsal plication/Nesbitt). This technique is not always without sexual function consequences including the potential to result in penile shortening and/or glans desensitization in a minority of patients. Two techniques typically reserved for high grade chordee (40 degrees or more) were found to be significantly associated with erectile dysfunction including division/resection of urethral plate (26/56 vs. 30/56, p = 0.02) and ventral corporoplasty (9/10 vs. 1/10, p = 0.0003) [33•]. From an anatomical perspective, it is difficult to explain how urethral plate transection can contribute to subsequent erectile dysfunction, though it is theorized that ventral corporoplasty may result in aneurysmal dilation and venous leak, predisposing patients to erectile dysfunction.

Fertility

Reproductive capability in adult patients with hypospadias can be influenced by surgical repair technique, incomplete chordee correction, as well as associated conditions with potential negative influences on reproduction including cryptorchidism and prematurity. Testicular dysgenesis syndrome hypothesizes that hypospadias, cryptorchidism, and testicular cancer are interlinked and stem from a distinct disturbance in embryologic testicular development [34]. As such, some studies have focused on the evaluation of the reproductive hormone status and sperm analysis of adult hypospadias patients. Kumar and colleagues studied the fertility potential parameters of 73 adult male patients with history of isolated hypospadias and found patients to have lower testosterone levels (average 465) compared to age matched controls (average 570) as well as a slightly larger discrepancy when proximal hypospadias patients are compared separately (average 459) [35]. Adult male patients with hypospadias also had correspondingly higher follicle stimulating hormone (FSH) and luteinizing hormone (LH) values compared to the control group [35]. Despite the disparity between the two groups, these reproductive hormone values for the hypospadias group are well within an acceptable, normal value range. Rey and associates evaluated the prevalence of endocrine testicular dysfunction in adult males with isolated hypospadias and found significantly lower risk of testicular dysfunction (OR 0.13, 95% CI 0.05–0.36) compared to men with hypospadias and associated genital anomalies suggesting that most men with isolated hypospadias should have normal androgen end-organ function [35].

In a large cohort study of 533 men, Asklund and other investigators evaluated semen quality of adult men with a history of corrected hypospadias with and without associated genital anomalies and found that men with history of hypospadias along with cryptorchidism had reduced levels of sperm concentration and total sperm count [36]. In contrast, the majority of men with isolated hypospadias had normal semen parameters. Kumar and colleagues also evaluated semen quality of adult men with history of corrected hypospadias and found that men with history of hypospadias had poor semen parameters including semen volume, sperm concentration, morphology, and activity compared to age matched controls [35]. This discrepancy increased when proximal hypospadias males were compared to controls; however, all parameters were within lower-normal values with the exception of semen volume (1.25 ml vs. 1.7 ml) which was below normal rage (< 1.5 mL) [35]. These clinical significance of these findings are unclear, as recent publications have cited disapproval of the cut off ranges set forth by the World Health Organization (WHO), stating that the lower levels of “normal” are not reflective of men with full reproductive competence [37].

A proportion of men with history of hypospadias correction may suffer from post-testicular or ejaculatory disorder as the cause of reproductive insufficiency. Reported rates of poor ejaculation rates in the literature range from 6 to 52%, with highest rates reported in patients with a more severe phenotype and those with two-stage repairs compared to single-stage repairs [38, 39]. Ejaculatory insufficiency may be the result of aberrant anatomy including a prominent utricle or insufficient rhythmic contraction secondary to an underdeveloped bulbospongiosus muscle. In addition, antegrade ejaculate can be hindered by urethral stricture and absent smooth muscle surrounding the reconstructed neourethra. These patients are often present for evaluation of dribbling ejaculation, anejaculation, or for an infertility evaluation. An urethral diverticulum can cause some of these symptoms and can be repaired if so. Some patients have to milk the urethra due to small volume ejaculate. In some cases, antihistamines and alpha-adrenergic agonists can be used to increase volume of ejaculatory fluid, whereas more severe cases may require surgical sperm retrieval.

Paternity rates and use of assisted reproductive technology (ART) have been used as an imprecise estimate of fertility potential. Using a Swedish healthcare registry, Nordenvall and colleagues evaluated fertility of 6000 + men with a hypospadias diagnosis, compared to non-affected male siblings as well as the general population [40•]. This investigation found a lower likelihood of being registered as a biologic father in men with history of hypospadias, with the most significant difference seen in patients with a proximal hypospadias diagnosis (HR 0.58, 95% CI 0.42–0.81) [40•]. An association was also demonstrated between hypospadias diagnosis and need for ART [40•]. However, there was no association between hypospadias and a male infertility diagnosis when patients with a history of cryptorchidism are excluded. The higher utilization of ART was not removed by controlling for concomitant history of cryptorchidism and shared genetic factors (non-affected male siblings) suggestive of isolated contribution of hypospadias to demonstrated subfertility [40•]. A single institution evaluated the association of paternity rates with reoperation for urethral obstruction in adult patients with history of hypospadias [41]. All patients underwent a two-stage repair by a single surgeon; however, specifics of surgical technique and distribution of hypospadias severity among study participants were not disclosed [41]. Similarly, Kanematsu and associates found a significant decrease in paternity rates in patients with a history of re-operation for urethral obstruction compared to those with no history of reoperation for urethral obstruction [41]. Although our ability to draw conclusions is limited by a multitude of factors including specifics regarding surgical technique of initial repair and subsequent reoperation, urethral patency, and/or success of the urethral stricture procedure, these results cite a potential link of initial repair outcomes in childhood to fertility potential in adulthood.

Psychosexual Outcomes

Hypospadias patients are at an increased risk for psychosocial maladjustment related to genital appearance and function. The potential adverse effects of hypospadias and related procedures can have self-confidence, and future relationships with partners may often be overlooked with families during preoperative counseling and during initial follow-up after childhood repair. This may be secondary to the fact that implications of hypospadias and repair on psychosocial development and functioning may not become apparent until adolescence and young adulthood.

Tack and colleagues evaluated psychosexual outcomes of 193 young males aged 16–21 with a history of hypospadias repair in childhood [42•]. Eighty-six percent of males with a history of corrected hypospadias reported satisfaction with genital appearance as compared to 94% of age matched controls [42•]. A larger proportion of men with hypospadias found it difficult to discuss sexual topics and had increased fear of being mocked when naked related to shame, smaller penis size, and concern with penile aesthetics [42•]. Despite concern of cosmetic appearance, there is no difference in sexarche or intercourse frequency in a Swedish study comparing adult men born with hypospadias and age-matched controls [43]. High rates of sexual quality of life were reported between young men with hypospadias and controls (94.5% v. 97.3%), with lower reported satisfaction in men with a history of severe hypospadias phenotypes [43]. Another study showed no significant difference in marital rates between adult men born with hypospadias and controls supporting idea that men with hypospadias have similar social development to other healthy males. Older studies have found significantly higher rates of genital appearance dissatisfaction and sexual inhibition, which may be attributable to older surgical techniques with less cosmetically appealing outcomes and/or older age at time of hypospadias repair completion [44].

Surgeon and young adult patient perspectives on genital cosmesis were compared using hypospadias objective penile evaluation (HOPE) score and pediatric penile perception score (PPPS) [42•]. Results revealed poor correlation between patient and surgeon evaluation of corrected hypospadias cosmesis, with patients reporting higher appraisal than surgeons with greatest incongruence in patients with proximal phenotype [42•]. This study also found that patients’ overall psychosocial outcome was most influenced by number of surgeries as opposed to initial phenotype severity [42•]. These findings highlight the need to consider forgoing additional surgery in patients with cosmetic irregularity such as mild residual chordee or minor urethral malposition in an otherwise functionally restored penis. Particularly as we advocate for follow-up into adolescence and early adulthood, we must be mindful of the patient’s desire to correct cosmetic imperfections that may not be affecting urinary or sexual function.

Conclusions

Hypospadias-related strictures and complications is a challenge to adult reconstructive urologists due to the heterogeneity of patient phenotypes and the uncertainty of repair outcomes. The repercussions of hypospadias phenotype and subsequent repair extend beyond urinary function and can carry lifelong challenges related to erectile dysfunction, fertility, and interpersonal relations. In this challenging patient population, greater discussion between pediatric and adult reconstructive urologists is warranted to both understand long-term surgical outcomes to help guide surgical approach as well as adequately counsel patients and families on expectations.