Cryptorchidism

Did You Know?

• A retractile testis is more common than a truly undescended testis and does not require surgery.
• The cremasteric reflex is much more active in infant boys than in older men.

Causes

In most full-term infant boys with cryptorchidism and no other genital abnormalities, no cause can be identified, making it a common, sporadic, and idiopathic birth defect. A combination of genetic factors, maternal health, and environmental influences may disrupt the hormones and physical changes needed for testicular development. Severe prematurity and low birth weight are known factors. Exposure to endocrine disruptors, such as certain pesticides, has been proposed as a contributing role. Regular alcohol consumption during pregnancy (five or more drinks per week) is associated with a three-fold increase in risk compared to nondrinking mothers, and cigarette smoking is also a risk factor. Family history of undescended testicles or other genital development problems increases risk. Cryptorchidism occurs at much higher rates in congenital malformation syndromes such as Down syndrome, Prader–Willi syndrome, and Noonan syndrome. In vitro fertilization, maternal use of cosmetics, and pre-eclampsia are recognized risk factors. Androgen insensitivity syndrome and 5α-Reductase 2 deficiency often manifest with cryptorchidism. A study found a significant association between higher levels of the phthalate DEHP in pregnant mothers and incomplete testicular descent in their sons.

Mechanism

Before birth, the testes start as germ cells that travel into testicular cords on the gonadal ridge inside the abdomen. By the second month of pregnancy, male genes steer this tissue toward becoming a testis instead of an ovary. Between months three and five, Leydig cells start making testosterone, and Sertoli cells produce anti-Müllerian hormone, while germ cells turn into fetal spermatogonia. The testes stay up in the abdomen until the seventh month, when they begin moving through the inguinal canals into the scrotum. This descent is thought to happen in two stages. The first stage, moving across the abdomen to the inguinal canal opening, seems guided by anti-Müllerian hormone. The second stage, traveling through the canal into the scrotum, relies on androgens, especially testosterone. In rodents, androgens trigger the genitofemoral nerve to release calcitonin gene-related peptide, which makes the gubernaculum contract rhythmically, but this hasn't been confirmed in humans. Problems with the gubernaculum, or a lack of or insensitivity to anti-Müllerian hormone or androgens, can block descent. Some research hints that the testes might also secrete a paracrine hormone called descendin. After birth, a natural rise in gonadotropins and testosterone between the first and fourth months often helps the testes finish descending.

Treatment

The primary management of cryptorchidism is watchful waiting, because self-resolution is common. If inguinal testes have not descended after 4–6 months, orchiopexy is effective and is often performed by a pediatric urologist or pediatric surgeon. Since undescended testicles are unlikely to descend after the first months of life, waiting longer only delays treatment. Hormonal therapy with human chorionic gonadotropin (hCG) is sometimes attempted for testes in the inguinal canal, with reported success rates ranging from roughly 5% to 50%, likely due to varying criteria for distinguishing retractile testes. Hormone treatment can confirm Leydig cell responsiveness or induce penile growth, and some surgeons report facilitation of surgery. A newer hormonal intervention in Europe uses GnRH analogs such as nafarelin or buserelin, with similar success rates; some surgeons combine both treatments. Limited evidence suggests germ cell count may improve slightly after hormone treatment, but whether this leads to better sperm counts and fertility at maturity is not established. The cost of hormone treatment is less than surgery, and complications at appropriate doses are minimal, but many surgeons do not consider success rates high enough to warrant the trouble.

Other animals

Cryptorchidism, the failure of one or both testicles to descend, affects all domestic animals but is seen most often in stallions, boars, and dogs. Rates differ by species and breed, with companion animals and swine more prone than ruminants. Causes include genetics, environment, and epigenetics. In male dogs, the condition occurs in up to 10% of individuals and is among the most common birth defects in purebreds, affecting 11% overall and 14% of Siberian Huskies. The inheritance pattern is not fully understood but is believed to be recessive and likely polygenic. Testicles normally descend by 10 days of age; failure to do so by eight weeks is considered cryptorchidism. The condition may be bilateral, causing sterility, or unilateral, and can be inguinal or abdominal. Because it is inherited, affected dogs should not be bred and should be castrated. Removing retained testicles is recommended due to a 13.6 times higher risk of testicular cancer, especially Sertoli cell tumors, and an increased chance of testicular torsion. Commonly affected breeds include Alaskan Klee Kai, Boxer, Chihuahua, miniature Dachshund, Bulldog, Maltese, Miniature Schnauzer, Pekingese, Pomeranian, toy and miniature Poodle, Pug, Shetland Sheepdog, Siberian Husky, Whippet, and Yorkshire Terrier.