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European Journal of Pediatrics Apr 2017Hypospadias is one of the most common congenital anomalies in men. The condition is typically characterized by proximal displacement of the urethral opening, penile... (Review)
Review
UNLABELLED
Hypospadias is one of the most common congenital anomalies in men. The condition is typically characterized by proximal displacement of the urethral opening, penile curvature, and a ventrally deficient hooded foreskin. In about 70%, the urethral meatus is located distally on the penile shaft; this is considered a mild form that is not associated with other urogenital deformities. The remaining 30% are proximal and often more complex. In these cases, endocrinological evaluation is advised to exclude disorders of sexual differentiation, especially in case of concomitant unilateral or bilateral undescended testis. Although the etiology of hypospadias is largely unknown, many hypotheses exist about genetic predisposition and hormonal influences. The goal of hypospadias repair is to achieve cosmetic and functional normality, and currently, surgery is recommended between 6 and 18 months of age. Hypospadias can be corrected at any age with comparable complication risk, functional, and cosmetic outcome; however, the optimal age of repair remains conclusive. Although long-term overall outcome concerning cosmetic appearance and sexual function is fairly good, after correction, men may more often be inhibited in seeking sexual contact. Moreover, lower urinary tract symptoms occur twice as often in patients undergoing hypospadias repair and can still occur many years after the initial repair.
CONCLUSION
This study explores the most recent insights into the management of hypospadias. What is Known: • Guidelines advise referral for treatment between 6 and 18 months of age. • Cosmetic outcome is considered satisfactory in over 70% of all patients. What is New: • Long-term complications include urinary tract symptoms and sexual and cosmetic issues. • New developments allow a more individualized approach, hopefully leading to less complications and more patient satisfaction.
Topics: Disorders of Sex Development; Humans; Hypospadias; Male; Patient Satisfaction; Penis; Plastic Surgery Procedures; Urethra
PubMed: 28190103
DOI: 10.1007/s00431-017-2864-5 -
TheScientificWorldJournal Apr 2011Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located... (Review)
Review
Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications.
Topics: Diverticulum; Humans; Hypospadias; Male; Penis; Postoperative Complications; Plastic Surgery Procedures; Urethral Diseases; Urethral Stricture; Urinary Fistula
PubMed: 21516286
DOI: 10.1100/tsw.2011.76 -
European Heart Journal May 2022Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a...
AIMS
Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease.
METHODS AND RESULTS
Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02).
CONCLUSION
Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.
Topics: Adolescent; Cardiovascular Diseases; Carotid Intima-Media Thickness; Endothelium, Vascular; Heart Disease Risk Factors; Humans; Hypertension; Hypogonadism; Hypospadias; Male; Nitric Oxide; Reactive Oxygen Species; Risk Factors; Vasodilation; rho-Associated Kinases
PubMed: 35567552
DOI: 10.1093/eurheartj/ehac112 -
Journal of Pediatric Urology Aug 2022Current approaches to classifying hypospadias severity are based on meatus position. These classification tools lack precise reflection on the degree of urethral...
OBJECTIVE
Current approaches to classifying hypospadias severity are based on meatus position. These classification tools lack precise reflection on the degree of urethral hypoplasia and extent of urethral underdevelopment hence are not good representative of hypospadias severity. Here, an alternative classification system is introduced that objectively reflects the developmental pathology underlying this condition. The study goal was to appraise location of bifurcation in the corpus spongiosum (BCS) relative to the penile shaft as an indicator of hypospadias severity.
PATIENTS AND METHODS
Patients aged <18 years with primary hypospadias were included in the study. Urethral defect ratio (UDR) was calculated by dividing the extent of urethral defect (distance between the glandular knobs and BCS) relative to stretched penile length (SPL). Hypospadias severity was then categorized into three distinct grades (UDR <0.5, 0.5-0.99, ≥1.0). The Inter-Class Correlation (ICC) was evaluated to assess the intra- and inter-rater agreement between the reviewers of UDC ratio. Linear regression analysis was performed to estimate the correlation between UDC ratios and either plate objective scoring tool (POST) and Curvature degrees.
RESULTS
A total of 67 patients aged 12.3 ± 3.7 months with primary hypospadias were enrolled. UDR ranged between 0.2 and 1.3. A significant difference in hypospadias level was observed between UDR grades, which further correlated degree of curvature (P < 0.0001), urethral plate quality (P < 0.0001), and associated anomalies (P < 0.05). The Inter-Class Correlation (ICC) value to examine the intra- and inter-rater agreement between the two reviewers in UDC ratio was 0.998 (95% CI 0.998, 0.999). Regression analysis revealed that UDR and both POST and Curvature degree were significantly associated (P < 0.001).
CONCLUSIONS
A hypospadias severity scoring system based on embryological etiology and urethral hypoplasia and assessed relative to the penile shaft represents an objective, feasible, and consistent tool. These results clearly indicate that the reviewers have had excellent consistency/reliability across their consecutive readings. This new system can facilitate objective description of hypospadias-spectrum anomalies and thus support precise communication between individual surgeons and centers.
Topics: Male; Humans; Infant; Hypospadias; Reproducibility of Results; Urethra; Penis; Urologic Surgical Procedures, Male
PubMed: 35644790
DOI: 10.1016/j.jpurol.2022.05.001 -
Molecular and Cellular Endocrinology Mar 2011Hypospadias is one of the most common congenital malformations. It is considered to be a mild form of the 46,XY disorders of sex development (DSD), but its precise... (Review)
Review
Hypospadias is one of the most common congenital malformations. It is considered to be a mild form of the 46,XY disorders of sex development (DSD), but its precise etiology remains to be elucidated. Compromised androgen synthesis or effects can cause this frequent malformation, although the mutational analyses of the genes involved in androgen actions have identified abnormalities in only a very small portion of patients. The overwhelming majority of cases remain unexplained and hypospadias may be a highly heterogeneous condition subject to multiple genetic and environmental factors. We here review the recent advances in this field and discuss the potential interactions between the environment and genetics.
Topics: Animals; Endocrine Disruptors; Environmental Pollutants; Epigenomics; Estrogens; Female; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Genitalia, Male; Humans; Hypospadias; Male; Maternal Exposure; Mutation
PubMed: 21256920
DOI: 10.1016/j.mce.2011.01.006 -
Journal of Medical Genetics Aug 1988The telecanthus-hypospadias (BBB) syndrome is characterised by widely spaced inner ocular canthi and hypospadias of variable degree. Heterozygous females have... (Review)
Review
The telecanthus-hypospadias (BBB) syndrome is characterised by widely spaced inner ocular canthi and hypospadias of variable degree. Heterozygous females have telecanthus. We have summarised the historical and phenotypic findings of 21 patients in seven previous publications. We have also had the opportunity to evaluate personally 12 families with a total of 18 affected males. The most frequent anomalies in patients previously reported are telecanthus 21/21, hypospadias 19/21, cleft lip/palate or uvula 7/21, high, broad nasal bridge 15/15, cranial abnormality 6/21, congenital heart defect 5/21, cryptorchidism 9/21, and mental retardation 11/17. In our series, the most frequent anomalies include telecanthus 18/18, hypospadias 18/18, cleft lip/palate or uvula 8/18, high, broad nasal bridge 10/11, cranial abnormality 12/18, congenital heart defect 3/18, upper urinary tract anomaly 4/9, and mental retardation 10/12. There is also an increased incidence of like-sex twinning, 11/18 in our families. This syndrome must be more common than reflected in published reports. Based upon the observation that males are much more severely affected than females and the lack of male to male transmission, it appears that this condition is most likely to be inherited in an X linked fashion. Further elucidation of the phenotype and documentation of the inheritance is needed. The distinction between the telecanthus-hypospadias syndrome and the G syndrome also needs further clarification.
Topics: Abnormalities, Multiple; Cleft Lip; Cleft Palate; Diseases in Twins; Eyelids; Humans; Hypospadias; Male; Pedigree; Syndrome
PubMed: 3050099
DOI: 10.1136/jmg.25.8.536 -
JAMA Network Open Jul 2022Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies.
OBJECTIVE
To characterize the risk of major CHDs among boys born with hypospadias.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022.
EXPOSURE
Hypospadias.
MAIN OUTCOMES AND MEASURES
Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN.
RESULTS
Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers.
CONCLUSIONS AND RELEVANCE
In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias.
Topics: Child; Cluster Analysis; Cohort Studies; Female; Heart Defects, Congenital; Humans; Hypospadias; Infant; Male; Pregnancy; Prevalence; Retrospective Studies
PubMed: 35900762
DOI: 10.1001/jamanetworkopen.2022.24152 -
Journal of Pediatric Urology Feb 2009To use meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure... (Review)
Review
OBJECTIVE
To use meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure to pesticides.
MATERIALS AND METHODS
A search of Pub Med for original research published in English from January 1966 through March 2008 identified 552 studies, 90 of which were reviewed in detail. Nine studies met all study inclusion criteria. Two reviewers independently abstracted data from each included study. Any disagreements were resolved by consensus. Pooled risk ratios (PRRs) and confidence intervals (CIs) were calculated using both random and fixed effects models, along with statistical tests of homogeneity.
RESULTS
Elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure (PRR of 1.36, CI=1.04-1.77), and paternal occupational exposure (PRR of 1.19, CI=1.00-1.41). Subgroup analyses provided insights into needed designs for future studies. Notably, exposure assessment using a job-exposure matrix resulted in slightly higher estimated risk than agricultural occupation in fathers; but this effect was reversed in mothers, suggesting the importance of indirect and residential pesticide exposures in this group.
CONCLUSIONS
Despite potential exposure misclassification, which would tend to diminish observed associations, the previous literature indicates a modestly increased risk of hypospadias associated with pesticide exposure.
Topics: Child; Female; Global Health; Humans; Hypospadias; Incidence; Male; Maternal Exposure; Pesticides; Pregnancy; Risk Factors
PubMed: 18848807
DOI: 10.1016/j.jpurol.2008.08.006 -
Asian Journal of Andrology Jan 2007Hypospadias is the most common congenital anomaly of the penis. The problem usually develops sporadically and without an obvious underlying cause. The ectopically... (Review)
Review
Hypospadias is the most common congenital anomaly of the penis. The problem usually develops sporadically and without an obvious underlying cause. The ectopically positioned urethral meatus lies proximal to the normal site and on the ventral aspect of the penis, and in severe cases opens onto the scrotum or perineum. The foreskin on the ventral surface is deficient, while that on the dorsal surface is abundant, giving the appearance of a dorsal hood. Chordee is more common in severe cases. Cryptorchidism and inguinal hernia are the most common associated anomalies. The frequency of associated anomalies increases with the severity of hypospadias. For isolated anterior or middle hypospadias, laboratory studies are not usually necessary. Screening for urinary tract anomalies should be considered in patients with posterior hypospadias and in those with an anomaly of at least one additional organ system. The ideal age for surgical repair in a healthy child is between 6 and 12 months of age. Most cases can be repaired in a single operation and on an outpatient basis. Even patients with a less than perfect surgical result are usually able to enjoy a satisfactory sexual life.
Topics: Geography; Humans; Hypospadias; Incidence; Male; Penis
PubMed: 17187155
DOI: 10.1111/j.1745-7262.2007.00243.x -
Sexual Development : Genetics,... 2021This paper reviews the current knowledge on the environmental effects on penile development in humans. The specific focus is on endocrine-disrupting chemicals (EDCs), a... (Review)
Review
This paper reviews the current knowledge on the environmental effects on penile development in humans. The specific focus is on endocrine-disrupting chemicals (EDCs), a heterogeneous group of natural or manmade substances that interfere with endocrine function, and whether they can induce hypospadias and micropenis in male neonates. Epidemiological data and animal observations first raised suspicions about environmental effects, leading to the testis dysgenesis syndrome (TDS) hypothesis. More recent research has provided stronger indications that TDS may indeed be the result of the direct or indirect effects of EDCs. Drawing on epidemiological and toxicological studies, we also report on the effects of maternal diet and substances like pesticides, phthalates, bisphenol A, and polychlorinated biphenyls. Proximity to contamination hazards and occupational exposure are also suspected to contribute to the occurrence of hypospadias and micropenis. Lastly, the cumulative effects of EDCs and the possibility of transgenerational effects, with the penile development of subsequent generations being affected, raise concerns for long-term public health.
Topics: Animals; Endocrine Disruptors; Environmental Exposure; Humans; Hypospadias; Male; Penis; Polychlorinated Biphenyls
PubMed: 34438394
DOI: 10.1159/000517157