Hypospadias

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Hypospadias
Hypospadias-lg.jpg
Different types of hypospadias
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Specialty Urology, medical genetics

Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location on the head of the penis. It is the second-most common birth defect of the male reproductive system, affecting about one of every 250 males at birth, [3] although when including milder cases, is found in up to 4% of newborn males. [4] Roughly 90% of cases are the less serious distal hypospadias, in which the urethral opening (the meatus) is on or near the head of the penis (glans). The remainder have proximal hypospadias, in which the meatus is all the way back on the shaft of the penis, near or within the scrotum. Shiny tissue that typically forms the urethra instead extends from the meatus to the tip of the glans; this tissue is called the urethral plate.

Contents

In most cases, the foreskin is less developed and does not wrap completely around the penis, leaving the underside of the glans uncovered. Also, a downward bending of the penis, commonly referred to as chordee, may occur. [5] Chordee is found in 10% of distal hypospadias [3] and 50% of proximal hypospadias [6] cases at the time of surgery. Also, the scrotum may be higher than usual on either side of the penis (called penoscrotal transposition).

The cause of hypospadias is unknown; scientists have investigated both genetic and environmental mechanisms, such as prenatal hormones. [7] [8] Another model suggests hypospadias arises as a result of unerased epigenetic markers which canalize sexual development. [4] It most often occurs by itself, without other variations, although in about 10% of cases it may be part of disorder of sex development condition or a medical syndrome with multiple abnormalities. [9] [10]

The most common associated difference is an undescended testicle, which has been reported in around 3% of infants with distal hypospadias and 10% with proximal hypospadias. [11] The combination of hypospadias and an undescended testicle sometimes indicates a child has a difference of sex development condition, so additional testing may be recommended to make sure the child does not have congenital adrenal hyperplasia with salt wasting or a similar condition where immediate medical intervention is needed. [12] [13] Otherwise no blood tests or X-rays are routinely needed in newborns with hypospadias. [3]

Hypospadias can be a symptom or indication of a difference in sex development, [14] but some consider that the presence of hypospadias alone is not enough to classify someone as a person with a difference/variation in sex development or as intersex. In most cases, hypospadias is not associated with any other condition. [15] Hypospadias is sometimes considered as an intersex condition by several intersex rights activist groups, who consider the repositioning of a working urethra on a child too young to consent to be a human rights violation. [16] [17] [18]

Presentation

Genitalia showing major genital undermasculinization and hypospadias Wax human hermaphrodit genital 2.jpg
Genitalia showing major genital undermasculinization and hypospadias

A penis with hypospadias usually has a characteristic appearance. Not only is the meatus (urinary opening) lower than usual, but the foreskin is also often only partially developed, lacking the usual amount that would cover the glans on the underside, causing the glans to have a hooded appearance. However, newborns with partial foreskin development do not necessarily have hypospadias, as some have a meatus in the usual place with a hooded foreskin, called "chordee without hypospadias". [19]

In other cases, the foreskin (prepuce) is typical and the hypospadias is concealed. This is called "megameatus with intact prepuce". The condition is discovered during newborn circumcision or later in childhood when the foreskin begins to retract. A newborn with typical-appearing foreskin and a straight penis who is discovered to have hypospadias after the start of circumcision can have circumcision completed without concern for jeopardizing hypospadias repair. [20] [21]

Complications

There is noted to be an increase in erectile problems in people with hypospadias, particularly when associated with a chordee (down curving of the shaft). There is usually minimal interaction with ability to ejaculate in hypospadias providing the meatus remains distal. This can also be affected by the coexistence of posterior urethral valves. There is an increase in difficulties associated with ejaculation, however, including increased rate of pain on ejaculation and weak/dribbling ejaculation. The rates of these problems are the same regardless of whether or not the hypospadias is surgically corrected. [22]

Cause

Genes and prenatal hormones

Hypospadias is present at birth, although the cause of hypospadias remains unknown. The influence of genes and the intrauterine environment have been proposed. [7] Sexual differentiation of males and female fetuses occurs under the influence of prenatal sex hormones. In humans, the development of external genitalia occurs in during an early hormone independent phase (5 to 8 weeks of gestation) and a later hormone dependent stage (weeks 8 to 12). One hypothesis proposes that atypical androgen exposure, or interference in the differentiation process, produces hypospadias. [8]

Epigenetic inheritance hypothesis

When one identical twin is born with hypospadias, his identical twin also has the trait only 25% of the time, despite sharing their genes and prenatal hormonal environment. [23] Animal studies have found that androgen antagonists during early fetal development cause elevated rates of hypospadias and cryptorchidism, however, in humans these traits rarely occur together. [23] In addition, levels of circulating testosterone overlap for both male and female fetuses throughout fetal development. Rice et al. have proposed that sexually dimorphic development occurs through epigenetic markers which are laid down during stem cell development, which blunt androgen signalling in XX fetuses, and boost sensitivity in XY fetuses. [4] If this marks are sexually antagonistic, and if a subset of these epigenetic marks carry over generations, they are expected to produce mosaicism of sexual development in opposite-sex offspring, sometimes producing hypospadias or cryptorchidism when passed from a mother to son (feminizing the external genitalia). Two small sample studies in 2012 and 2013 found changes in the transcriptome and methylome of hypospadias patients. [4] A 2022 study found additional evidence of atypical epigenetic methylation in foreskin tissue of hypospadias patients. [24] Rice's model requires further testing with currently available technology to support or falsify it. [4]

Treatment

Where hypospadias is seen as a genital ambiguity in a child, the World Health Organization standard of care is to delay surgery until the child is old enough to participate in informed consent, unless emergency surgery is needed because the child lacks a urinary opening. Hypospadias is not a serious medical condition. A urinary opening that is not surrounded by glans tissue is more likely to "spray" the urine, which can cause a person to sit to urinate because they cannot reliably stand and hit the toilet. Chordee is a separate condition, but where it occurs, the downward curvature of the penis may be enough to make sexual penetration more difficult. For these reasons or others, people with hypospadias may choose to seek urethroplasty, a surgical extension of the urethra using a skin graft. [ citation needed ]

Surgery can extend the urinary channel to the end of the penis, straighten bending, and/or change the foreskin (by either circumcision or by altering its appearance to look more typical ("preputioplasty"), depending on the desire of the patient. Urethroplasty failure rates vary enormously, from around 5% for the simplest repairs to damage in a normal urethra by an experienced surgeon, to 15-20% when a buccal graft from the inside of the mouth can be used to extend a urethra, to close to 50% when graft urethral tubes are constructed from other skin. [25]

When the hypospadias is extensive–third degree/penoscrotal–or has associated differences in sex development such as chordee or cryptorchidism, the best management can be a more complicated decision. The world standard (UN and WHO) forbids nonessential surgery to produce a "normal" appearance without the informed consent of the patient, [26] and the American Academy of Pediatrics currently recommends but does not require the same standard. The AAP Textbook of Pediatric Care states "Gender assignment in patients with genital ambiguity should be made only after careful investigation by a multidisciplinary team; increasingly, surgical decisions are delayed until the child is able to participate in the decision-making process." [27] A karyotype and endocrine evaluation should be performed to detect intersex conditions or hormone deficiencies that have major health risks (i.e. salt-wasting). If the penis is small, testosterone or human chorionic gonadotropin (hCG) injections may be given with consent to enlarge it before surgery if this will increase the chance of a successful urethral repair. [3]

Surgical repair of severe hypospadias may require multiple procedures and mucosal grafting. Preputial skin is often used for grafting and circumcision should be avoided before repair. In patients with severe hypospadias, surgery often produces unsatisfactory results, such as scarring, curvature, or formation of urethral fistulas, diverticula, or strictures. A fistula is an unwanted opening through the skin along the course of the urethra, and can result in urinary leakage or an abnormal stream. A diverticulum is an "outpocketing" of the lining of the urethra which interferes with urinary flow and may result in posturination leakage. A stricture is a narrowing of the urethra severe enough to obstruct flow. Reduced complication rates even for third-degree repair (e.g., fistula rates below 5%) have been reported in recent years from centers with the most experience. [28] However, typical complications in urethroplasty for severe hypospadias can lead to long surgical cycles of failure and repair, and side effects may include loss of sexual or urinary function. [29] Research suggests failure rates are higher when urethroplasty corrects a born condition rather than disease or injury [30] so patients and families considering surgery for hypospadias should have realistic expectations about the risks and benefits. [31]

Age at surgery

The results of surgery are probably not influenced by the age at which repair is done. [32] [33] Teens and adults typically spend one night in the hospital after surgery.[ citation needed ]

Preoperative hormones

Hormones potentially increase the size of the penis, and have been used in children with proximal hypospadias who have a smaller penis. Numerous articles report testosterone injections or topical creams increase the length and circumference of the penis. However, few studies discuss the impact of this treatment on the success of corrective surgery, with conflicting results. [33] [34]

Surgery

Surgery is not always required for minor hypospadias like glanular hypospadias and coronal hypospadias if the meatus is of good caliber, urine flow is in good stream & forwardly directed. [35]

Hypospadias repair is done under general anesthesia, most often supplemented by a nerve block to the penis or a caudal block to reduce the general anesthesia needed, and to minimize discomfort after surgery.[ citation needed ]

Many techniques have been used during the past 100 years to extend the urinary channel to the desired location. Today, the most common operation, known as the tubularized incised plate or "TIP" repair, rolls the urethral plate from the low meatus to the end of the glans. TIP repair, also called the Snodgrass Repair (after the creator of the method, Dr. Warren Snodgrass), is the most widely used procedure and surgical method for hypospadias repair worldwide. This procedure can be used for all distal hypospadias repairs, with complications afterwards expected in less than 10% of cases. [36] [37]

Less consensus exists regarding proximal hypospadias repair. [38] TIP repair can be used when the penis is straight or has mild downward curvature, with success in 85%. [36] Alternatively, the urinary channel can be reconstructed using the foreskin, with reported success in from 55% to 75%. [39]

Most distal and many proximal hypospadias are corrected in a single operation. However, those with the most severe condition having a urinary opening in the scrotum and downward bending of the penis are often corrected in a two-stage operation. During the first operation the curvature is straightened. At the second, the urinary channel is completed. Any complications may require additional interventions for repair.[ citation needed ]

Outcomes

Problems that can arise include a small hole in the urinary channel below the meatus, called a fistula. The head of the penis, which is open at birth in children with hypospadias and is closed around the urinary channel at surgery, sometimes reopens, known as glans dehiscence. The new urinary opening can scar, resulting in meatal stenosis, or internal scarring can create a stricture, either of which cause partial blockage to urinating. If the new urinary channel balloons when urinating a child is diagnosed with a diverticulum.[ citation needed ]

Most complications are discovered within six months after surgery, although they occasionally are not found for many years. In general, when no problems are apparent after repair in childhood, new complications arising after puberty are uncommon. However, some problems that were not adequately repaired in childhood may become more pronounced when the penis grows at puberty, such as residual penile curvature or urine spraying due to rupture of the repair at the head of the penis.[ citation needed ]

Complications are usually corrected with another operation, most often delayed for at least six months after the last surgery to allow the tissues to heal sufficiently before attempting another repair. Results when circumcision or foreskin reconstruction are done are the same. [40] [41] (Figure 4a, 4b)

Patients and surgeons had differing opinions as to outcomes of hypospadias repair, that is, patients might not be satisfied with a cosmetic result considered satisfactory by the surgeon, but patients with a cosmetic result considered not very satisfactory by the surgeon may themselves be satisfied. Overall, patients were less satisfied than surgeons. [22]

Living with hypospadias can present challenging emotional obstacles. Many men, whether they have had surgical repair of their hypospadias as a child or not often are very guarded in school bathrooms or locker rooms. Secrecy about the condition can complicate emotional pain, because talking about the penis is often a taboo subject. Worry, anxiety and feelings of shame are common among adult men born with hypospadias. [42]

Epidemiology

Hypospadias is among the most common birth defects in the world and is said to be the second-most common birth defect in the male reproductive system, occurring once in every 250 males. [43] When including milder cases, it is seen in as many as 4% of newborn male babies. [4]

Due to variations in the reporting requirements of different national databases, data from such registries cannot be used to accurately determine either incidence of hypospadias or geographical variations in its occurrences. [3]

Adults

While most hypospadias repairs are done in childhood, occasionally, an adult desires surgery because of urinary spraying or unhappiness with the appearance.

A direct comparison of surgical results in children versus adults found they had the same outcomes, and adults can undergo hypospadias repair or reoperations with good expectations for success. [33]

Society and culture

Notable individuals with hypospadias: (sources and citation needed)

See also

Related Research Articles

<span class="mw-page-title-main">Urethra</span> Tube that connects the urinary bladder to the external urethral orifice

The urethra is a tube that connects the mammalian urinary bladder to the urinary meatus. Male and female placental mammals release urine through the urethra during urination, but males also release semen through the urethra during ejaculation.

<span class="mw-page-title-main">Glans penis</span> End of the penis

In male human anatomy, the glans penis or penile glans, commonly referred to as the glans, is the bulbous structure at the distal end of the human penis that is the human male's most sensitive erogenous zone and primary anatomical source of sexual pleasure. The glans penis is present in the male reproductive organs of humans and most other mammals where it may appear smooth, spiny, elongated or divided. It is externally lined with mucosal tissue, which creates a smooth texture and glossy appearance. In humans, the glans is located over the distal ends of the corpora cavernosa and is a continuation of the corpus spongiosum of the penis. At the summit appears the urinary meatus and at the base forms the corona glandis. An elastic band of tissue, known as the frenulum, runs on its ventral surface. In men who are not circumcised, it is completely or partially covered by a fold of skin called the foreskin. In adults, the foreskin can generally be retracted over and past the glans manually or sometimes automatically during an erection.

<span class="mw-page-title-main">Paraphimosis</span> Medical condition

Paraphimosis is an uncommon medical condition in which the foreskin of a penis becomes trapped behind the glans penis, and cannot be reduced. If this condition persists for several hours or there is any sign of a lack of blood flow, paraphimosis should be treated as a medical emergency, as it can result in gangrene.

<span class="mw-page-title-main">Phimosis</span> Medical condition

Phimosis is a condition in which the foreskin of the penis cannot stretch to allow it to be pulled back past the glans. A balloon-like swelling under the foreskin may occur with urination. In teenagers and adults, it may result in pain during an erection, but is otherwise not painful. Those affected are at greater risk of inflammation of the glans, known as balanitis, and other complications.

<span class="mw-page-title-main">Urethral stricture</span> Medical condition

A urethral stricture is a narrowing of the urethra, the tube connected to the bladder that allows the passing of urine. The narrowing reduces the flow of urine and makes it more difficult or even painful to empty the bladder.

<span class="mw-page-title-main">Chordee</span> Medical condition

Chordee is a condition in which the head of the penis curves downward or upward, at the junction of the head and shaft of the penis. The curvature is usually most obvious during erection, but resistance to straightening is often apparent in the flaccid state as well. In many cases but not all, chordee is associated with hypospadias. This is not the same condition as Peyronie's disease, which involves curvature of the shaft of the penis most commonly due to injury during adult life.

<span class="mw-page-title-main">Meatotomy</span> Surgical modification of the male urinary meatus

A meatotomy is a form of penile modification in which the underside of the glans is split, extending the urinary meatus. The procedure may be performed by a doctor to alleviate meatal stenosis or urethral stricture.

<span class="mw-page-title-main">Intersex medical interventions</span> Performed to modify atypical or ambiguous genitalia

Intersex medical interventions (IMI), sometimes known as intersex genital mutilations (IGM), are surgical, hormonal and other medical interventions performed to modify atypical or ambiguous genitalia and other sex characteristics, primarily for the purposes of making a person's appearance more typical and to reduce the likelihood of future problems. The history of intersex surgery has been characterized by controversy due to reports that surgery can compromise sexual function and sensation, and create lifelong health issues. The medical interventions can be for a variety of reasons, due to the enormous variety of the disorders of sex development. Some disorders, such as salt-wasting disorder, can be life-threatening if left untreated.

Urethral meatal stenosis is a narrowing (stenosis) of the opening of the urethra at the external meatus, thus constricting the opening through which urine leaves the body from the urinary bladder.

A urethrotomy is an operation which involves incision of the urethra, especially for relief of a stricture. It is most often performed in the outpatient setting, with the patient (usually) being discharged from the hospital or surgery center within six hours from the procedure's inception.

<span class="mw-page-title-main">Urinary meatus</span> Orifice of the urethra

The urinary meatus, also known as the external urethral orifice, is the opening where urine exits the male and female urethra. It is where semen also exits the male urethra. The meatus has varying degrees of sensitivity to touch.

<span class="mw-page-title-main">Human penis</span> Human male external reproductive organ

In human anatomy, the penis is an external male sex organ that additionally serves as the urinary duct. The main parts are the root, body, the epithelium of the penis including the shaft skin, and the foreskin covering the glans. The body of the penis is made up of three columns of tissue: two corpora cavernosa on the dorsal side and corpus spongiosum between them on the ventral side. The urethra passes through the prostate gland, where it is joined by the ejaculatory duct, and then through the penis. The urethra goes across the corpus spongiosum and ends at the tip of the glans as the opening, the urinary meatus. It is a passage both for excretion of urine and the ejaculation of semen.

Urethroplasty is the surgical repair of an injury or defect within the walls of the urethra. Trauma, iatrogenic injury and infections are the most common causes of urethral injury/defect requiring repair. Urethroplasty is regarded as the gold standard treatment for urethral strictures and offers better outcomes in terms of recurrence rates than dilatations and urethrotomies. It is probably the only useful modality of treatment for long and complex strictures though recurrence rates are higher for this difficult treatment group.

<span class="mw-page-title-main">Retrograde urethrogram</span> Medical imaging of the urethra

A retrograde urethrography is a routine radiologic procedure used to image the integrity of the urethra. Hence a retrograde urethrogram is essential for diagnosis of urethral injury, or urethral stricture.

<span class="mw-page-title-main">Diphallia</span> Genital medical condition

Diphallia, penile duplication (PD), diphallic terata, or diphallasparatus is an extremely rare developmental abnormality in which a male is born with two penises. The first reported case was by Johannes Jacob Wecker in 1609. Its occurrence is 1 in 5.5 million boys in the United States.

<span class="mw-page-title-main">Foreskin</span> Retractable fold of skin which covers and protects the glans of the penis

In male human anatomy, the foreskin, also known as the prepuce, is the double-layered fold of skin, mucosal and muscular tissue at the distal end of the human penis that covers the glans and the urinary meatus. The foreskin is attached to the glans by an elastic band of tissue, known as the frenulum. The outer skin of the foreskin meets with the inner preputial mucosa at the area of the mucocutaneous junction. The foreskin is mobile, fairly stretchable and sustains the glans in a moist environment. Except for humans, a similar structure known as a penile sheath appears in the male sexual organs of all primates and the vast majority of mammals.

<span class="mw-page-title-main">Buried penis</span> Male congenital condition

Buried penis, also called hidden penis or retractile penis, is a congenital or acquired condition in which the penis is partially or completely hidden below the surface of the skin. A buried penis can lead to urinary difficulties, poor hygiene, infection, and inhibition of normal sexual function.

Male genital examination is a physical examination of the genital in males to detect ailments and to assess sexual development, and is normally a component of an annual physical examination. The examination includes checking the penis, scrotum, and urethral meatus. A comprehensive assessment of the male genitals assesses the pubic hair based on Sexual Maturity Rating and the size of the testicles and penis. The exam can also be conducted to verify a person's age and biological sex. The genitourinary system can also be assessed as part of the male genital examination. During a genital examination, the doctor can detect any of the following: structural abnormalities, urethral opening abnormalities, problems related to not being circumcised, lumps, tumors, redness, excoriation, edema, lesions, swelling, cancer, hair-related issues, and many others. In some instances where a physical examination of the male genitals is not sufficient to diagnose an individual, then an internal genital examination using imaging or ultrasounds will be needed for further evaluation.

<span class="mw-page-title-main">Warren Snodgrass</span>

Warren Snodgrass is a pediatric urologist specializing in the repair of hypospadias, the second most common birth defect. In 1994 he described the tubularized incised plate (TIP) repair of hypospadias, which has become known as the Snodgrass repair and has become the most common approach to repairing most forms of hypospadias. Together with Dr. Nicol Bush, he also developed the STAG repair for severe hypospadias, which later evolved into STAC. Snodgrass is internationally known for his advocacy of evidence-based surgery, and was the editor of a textbook on pediatric urology. He is in private practice near Dallas, Texas, where he is the co-director of the Hypospadias Specialty Center.

A penile injury is a medical emergency that afflicts the penis. Common injuries include fracture, avulsion injury, strangulation, entrapment, and amputation.

References

  1. ↑ Entry "hypospadias" in Merriam-Webster Online Dictionary .
  2. ↑ OED 2nd edition, 1989 as /hɪpəʊˈspeɪdɪəs/~/haɪpəʊˈspeɪdɪəs/
  3. 1 2 3 4 5 Snodgrass W (2012). "Chapter 130: Hypospadias". In Wein A, Campbell MF, Walsh PC (eds.). Campbell-Walsh Urology, Tenth Edition. Elsevier. pp. 3503–3536. ISBN   978-1-4160-6911-9.
  4. 1 2 3 4 5 6 Rice, William R.; Friberg, Urban; Gavrilets, Sergey (2016). "Sexually antagonistic epigenetic marks that canalize sexually dimorphic development" (PDF). Molecular Ecology. 25 (8): 1812–1822. doi:10.1111/mec.13490. ISSN   0962-1083.
  5. ↑ King S, Beasley S (2012) [1st. Pub. 1986]. "Chapter 9.1:Surgical Conditions in Older Children". In South M (ed.). Practical Paediatrics, Seventh Edition. Churchill Livingstone, Elsevier. pp. 266–267. ISBN   978-0-702-04292-8.
  6. ↑ Snodgrass W, Prieto J (October 2009). "Straightening ventral curvature while preserving the urethral plate in proximal hypospadias repair". The Journal of Urology. 182 (4 Suppl): 1720–5. doi:10.1016/j.juro.2009.02.084. PMID   19692004.
  7. 1 2 "Hypospadias - Symptoms and causes". Mayo Clinic. Retrieved 2023-12-13.
  8. 1 2 Bouty, Aurore; Ayers, Katie L.; Pask, Andrew; Heloury, Yves; Sinclair, Andrew H. (2015-11-28). "The Genetic and Environmental Factors Underlying Hypospadias". Sexual Development. 9 (5): 239–259. doi:10.1159/000441988. ISSN   1661-5425.
  9. ↑ Stoll C, Alembik Y, Roth MP, Dott B (September 1990). "Genetic and environmental factors in hypospadias". Journal of Medical Genetics. 27 (9): 559–63. doi:10.1136/jmg.27.9.559. PMC   1017217 . PMID   2231648.
  10. ↑ Calzolari E, Contiero MR, Roncarati E, Mattiuz PL, Volpato S (August 1986). "Aetiological factors in hypospadias". Journal of Medical Genetics. 23 (4): 333–7. doi:10.1136/jmg.23.4.333. PMC   1049700 . PMID   3746833.
  11. ↑ Wu H, Wei Z, M G (2002). "Hypospadias and enlarged prostatic utricle". Chinese Journal of Urology. 12: 51–3.
  12. ↑ Kaefer M, Tobin MS, Hendren WH, Bauer SB, Peters CA, Atala A, et al. (April 1997). "Continent urinary diversion: the Children's Hospital experience". The Journal of Urology. 157 (4): 1394–9. doi:10.1016/S0022-5347(01)64998-X. PMID   9120962.
  13. ↑ Tarman GJ, Kaplan GW, Lerman SL, McAleer IM, Losasso BE (January 2002). "Lower genitourinary injury and pelvic fractures in pediatric patients". Urology. 59 (1): 123–6, discussion 126. doi:10.1016/S0090-4295(01)01526-6. PMID   11796295.
  14. ↑ "Explaining Disorders of Sex Development & Intersexuality".
  15. ↑ Tidy, Colin (January 19, 2016). "Hypospadias". Patient. Patient Platform Ltd. Retrieved October 18, 2018.
  16. ↑ "What is intersex? Frequently Asked Questions and Intersex Definitions". interACT. Retrieved May 7, 2021.
  17. ↑ "Alice Dreger: Do you have to pee standing up to be a real man? – Intersex Human Rights Australia". ihra.org.au. 2014-02-14. Retrieved 2022-03-22.
  18. ↑ "IGM". OII Europe. 2021-02-04. Retrieved 2022-03-22.
  19. ↑ Singh S, Rawat J, Kureel SN, Pandey A. Chordee without hypospadias: Operative classification and its management. Urol Ann. 2013 Apr;5(2):93-8. doi : 10.4103/0974-7796.110005. PMID   23798865; PMCID: PMC3685753.
  20. ↑ Snodgrass WT, Khavari R (July 2006). "Prior circumcision does not complicate repair of hypospadias with an intact prepuce". The Journal of Urology. 176 (1): 296–8. doi:10.1016/S0022-5347(06)00564-7. PMID   16753427.
  21. ↑ Chalmers D, Wiedel CA, Siparsky GL, Campbell JB, Wilcox DT (May 2014). "Discovery of hypospadias during newborn circumcision should not preclude completion of the procedure". The Journal of Pediatrics. 164 (5): 1171–1174.e1. doi:10.1016/j.jpeds.2014.01.013. PMID   24534572.
  22. 1 2 Mieusset R, Soulié M (2005). "Hypospadias: psychosocial, sexual, and reproductive consequences in adult life". Journal of Andrology. 26 (2): 163–8. doi: 10.1002/j.1939-4640.2005.tb01078.x . PMID   15713818.
  23. 1 2 Rice, William R.; Friberg, Urban; Gavrilets, Sergey (2012). "Homosexuality as a Consequence of Epigenetically Canalized Sexual Development" (PDF). The Quarterly Review of Biology. 87 (4): 355–356. doi:10.1086/668167. ISSN   0033-5770.
  24. ↑ Kaefer, Martin; Rink, Richard; Misseri, Rosalia; Winchester, Paul; Proctor, Cathy; Ben Maamar, Millissia; Beck, Daniel; Nilsson, Eric; Skinner, Michael K. (2023-01-11). "Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations". Scientific Reports. 13 (1): 555. doi: 10.1038/s41598-023-27763-5 . ISSN   2045-2322.
  25. ↑ "Urethroplasty". Department of Urology. 2016-06-06. Retrieved 2019-06-14.
  26. ↑ "United Nations Fact Sheet-Intersex" (PDF).
  27. ↑ Loomba-Albrecht, Lindsey A.; Styne, Dennis M. (2017). "Disorders of Sex Development". American Academy of Pediatrics Textbook of Pediatric Care (2nd ed.). ISBN   978-1-61002-579-9.
  28. ↑ "Re operation with Dr Nicol Bush & Dr Warren Snodgrass". PARC Urology Hypospadias Center. 2016-07-15. Retrieved 2019-05-09.
  29. ↑ Bayne, Aaron P.; Jones, Eric A. (2010). "Complications of hypospadias repair". In Taneja, Samir S. (ed.). Complications of Urologic Surgery (4th ed.). W.B. Saunders. pp. 713–722. ISBN   978-1-4160-4572-4.
  30. ↑ Suh JG, Choi WS, Paick JS, Kim SW (July 2013). "Surgical Outcome of Excision and End-to-End Anastomosis for Bulbar Urethral Stricture". Korean Journal of Urology. 54 (7): 442–7. doi:10.4111/kju.2013.54.7.442. PMC   3715707 . PMID   23878686.
  31. ↑ "What are some of the risks of penile surgery?". ISSM. 2012-02-21. Retrieved 2019-06-14.
  32. ↑ Warren T. Snodgrass (2013-05-13). Pediatric Urology: Evidence for Optimal Patient Management. Springer Science & Business Media. pp. 117–. ISBN   978-1-4614-6910-0.
  33. 1 2 3 Bush N, Snodgrass W (August 2014). "Response to "Re: Snodgrass W, et al. Duration of follow-up to diagnose hypospadias urethroplasty complications. J Pediatr Urol 2014;10:783-784"". Journal of Pediatric Urology. 10 (4): 784–5. doi:10.1016/j.jpurol.2014.04.022. PMID   24999242.
  34. ↑ Kaplan GW (September 2008). "Does administration of transdermal dihydrotestosterone gel before hypospadias repair improve postoperative outcomes?". Nature Clinical Practice. Urology. 5 (9): 474–5. doi:10.1038/ncpuro1178. PMID   18679395. S2CID   22512786.
  35. ↑ "Hypospadias" . Retrieved 2023-03-21.
  36. 1 2 Snodgrass WT, Bush N, Cost N (August 2010). "Tubularized incised plate hypospadias repair for distal hypospadias". Journal of Pediatric Urology. 6 (4): 408–13. doi:10.1016/j.jpurol.2009.09.010. PMID   19837000.
  37. ↑ Wilkinson DJ, Farrelly P, Kenny SE (June 2012). "Outcomes in distal hypospadias: a systematic review of the Mathieu and tubularized incised plate repairs". Journal of Pediatric Urology. 8 (3): 307–12. doi:10.1016/j.jpurol.2010.11.008. PMID   21159560.
  38. ↑ Castagnetti M, El-Ghoneimi A (October 2010). "Surgical management of primary severe hypospadias in children: systematic 20-year review". The Journal of Urology. 184 (4): 1469–74. doi:10.1016/j.juro.2010.06.044. PMID   20727541.
  39. ↑ Warren T. Snodgrass (2013-05-13). Pediatric Urology: Evidence for Optimal Patient Management. Springer Science & Business Media. pp. 129–. ISBN   978-1-4614-6910-0.
  40. ↑ Suoub M, Dave S, El-Hout Y, Braga LH, Farhat WA (October 2008). "Distal hypospadias repair with or without foreskin reconstruction: A single-surgeon experience". Journal of Pediatric Urology. 4 (5): 377–80. doi:10.1016/j.jpurol.2008.01.215. PMID   18790424.
  41. ↑ Snodgrass W, Dajusta D, Villanueva C, Bush N (August 2013). "Foreskin reconstruction does not increase urethroplasty or skin complications after distal TIP hypospadias repair". Journal of Pediatric Urology. 9 (4): 401–6. doi:10.1016/j.jpurol.2012.06.008. PMID   22854388.
  42. ↑ Filippelli, John (2021). Living With Hypospadias. Palmetto Publishing. pp. 24–30. ISBN   978-1638372172.
  43. ↑ Gatti JM. "Epidemiology". Medscape Reference. Retrieved 22 January 2013.
  44. ↑ "The "infertility" of Catherine de Medici and its influence on 16th century France" (PDF).
  45. ↑ "Male or female? Babies born on the sliding sex scale". British Broadcasting Corporation . 11 October 2011. Retrieved 2016-05-12.
  46. ↑ Littlefield, Amy (August 13, 2018). "Intersex People Want to End Nonconsensual Surgeries. A California Resolution Is Their 'Warning Shot.'". Rewire.News . Retrieved 2018-11-30.
  47. ↑ Intersexualidad: «Nunca me sentí niña y mi comportamiento masculino era un problema». ABC. 20 October 2014.
  48. ↑ La barba me dio la razón: aunque me criaran como una niña, yo era un niño. El País. 30 June 2016.
  49. ↑ Lieberman, Hallie (August 29, 2018). "The Trigger Effect". The Atavist Magazine. No. 82. Archived from the original on September 1, 2018. Retrieved 2018-08-31.
  50. ↑ Heifetz, Danny, When a Dick Joke Isn't a Joke, theringer.com, March 2020

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