What causes cryptorchidism?

Updated: Dec 17, 2020
  • Author: Joel M Sumfest, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

The etiology of cryptorchidism is multifactorial. Extensive research and clinical observations have elucidated some of the factors involved, but the exact mechanism of cryptorchidism has proved elusive.

Birth weight is the principal determining factor for undescended testes at birth to age 1 year, independent of the length of gestation.

One study found that almost 23% of index patients with undescended testes had a positive family history of cryptorchidism, as opposed to 7.5% in control families. [3] The familial cluster is 3.6 fold overall, 6.9 if a brother is affected and 4.6 if the father. Mutations in the homeobox gene HOXA10, which plays a pivotal role in regulation of testicular descent, may be involved in select cases. [4, 5]

Transabdominal descent of the testis involves differential growth of vertebrae and pelvis until 23 weeks’ gestation. Afterward, further descent is facilitated by the development of the gubernaculum, processus vaginalis, spermatic vessels, and scrotum. [2] A normal hypothalamic-pituitary-gonadal axis is a prerequisite for testicular descent. [6] Furthermore, testosterone and its conversion to dihydrotestosterone (DHT) are also necessary for continued migration, especially during the inguinoscrotal phase. [7, 8, 9]

Exposure to endocrine-disrupting chemicals may contribute to cryptorchidism, and may account for the increasing incidence rate of cryptorchidism seen in some regions. Synthetic chemicals identified as endocrine disruptors include phthalates, pesticides, brominated flame retardants, diethylstilbestrol, and dioxins. [10] Different studies have found conflicting data regarding the involvement of müllerian-inhibiting substance, prenatal estrogen exposure, and descendin (a specific gubernacular growth factor) in the pathophysiology of cryptorchidism. [11, 12, 13]

Although its exact mechanism of action is unclear, the gubernaculum has significant importance in undescended testes. In patients with cryptorchidism, the gubernaculum is not firmly attached to the scrotum, and the testis is not pulled into the scrotum. [14] Both hormonal and mechanical factors appear to mediate the aid of the gubernaculum and descent of the testis. [15] The genitofemoral nerve may also aid in descent and gubernacular differentiation, which may be mediated by calcitonin gene-related peptide. [16, 17]

Intra-abdominal pressure also appears to play a role in testicular descent. Conditions associated with decreased pressure include prune belly syndrome, cloacal exstrophy, omphalocele, and gastroschisis, among other various syndromes. Each is associated with an increased risk of undescended testes. [18, 19] The effect of decreased intra-abdominal pressure is most significant during transinguinal migration to the scrotum, probably in conjunction with androgens and a patent processus vaginalis. [20, 21]

Epididymal abnormalities often accompany undescended testes, but the causal relationship has not been established. In 1992, Elder concluded that most epididymal abnormalities probably do not contribute to maldescent. [22]

A Japanese study found that nationwide, the discharge rate of cryptorchidism increased by 14.3% after the Fukushima nuclear accident. Rates of other risk factors for cryptorchidism (ie, low-weight babies, preterm births) remained almost constant during the study period, and age distribution of cryptorchidism surgery also did not change. [23]


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