Anorchia and Cryptorchidism

Cryptorchidism occurs when one (unilateral cryptorchidism, 85% of cases) or both testicles (bilateral cryptorchidism, 15% of cases) fail to descend into the scrotal bursa. It is the most common genital variation in people with 46,XY karyotype, with a prevalence ranging from 1.6% to 8.4%. Generally, during the first 7–8 months of fetal life, the testicles migrate from the abdominal cavity (where they originate) into the groin through a passage called the inguinal canal, falling into the scrotal pouch in adults. Cryptorchidism occurs when one or both testicles fail to descend from the abdominal cavity into the scrotum. Occasionally, the testicle(s) stop(s) somewhere along the descent, ending up in an abdominal, inguinal (the most frequent), supra-scrotal, or high scrotal position. More rarely, the testicle ends up in an ectopic location, i.e., outside the path usually taken to reach their final position.

Cryptorchidism can be congenital –when present at birth–, or acquired, when the testicles that descended at birth return to their initial position, which typically occurs in the prepubertal period.

Anorchia is a Variation of Sex Characteristics (VSC)/ Difference of Sex Development (DSD) determined by the absence of testicles in people with a 46,XY karyotype and with a typically male phenotype. This variation affects 1 in 20,000 newborns with XY chromosomes, and is seen in 1/177 cases of cryptorchidism. Since the differentiation of the internal and external genitalia in a typically male line depends on the anti-Müllerian hormone (AMH) and testosterone –both of which are produced in the testicles– some people with anorchia have ambiguous external genitalia or a micropenis. In any case, most have male external and internal genitalia. This indicates the presence of normally functioning testicles (i.e. capable of synthesizing AMH and testosterone) during fetal life. In time, the testicles degenerate, reducing their hormone production.

Genetic traits
The aetiology of cryptorchidism is complex and includes genetic, hormonal, environmental, and maternal predisposing factors. As for anorchia, the possible association of several cases in the same family suggests a possible genetic cause, even if this remains unproven. Nevertheless, the use of exploratory laparoscopy has led to the hypothesis that, in some cases, anorchia is the consequence of a vascular problem in the pre-natal period, associated with torsion of the testicles during their descent into the scrotal bursa.

Identification
Both cryptorchidism and anorchia are clinically identified by the absence of testicles in the scrotal bursa. Therefore, to distinguish between these two conditions, we need to look for testicular tissue (present in cryptorchidism and absent in anorchia). Exams such as ultrasound and MRI, and possibly laparoscopic surgical exploration, are used to ascertain these conditions. Laboratory tests can also help distinguish between the two.

Medical options
In cryptorchidism, the testicles may descend into the scrotum spontaneously in the first year of life. If this should fail to occur, cryptorchidism must be corrected to avoid impaired fertility and an increased risk of testicular tumours in adulthood. To this end, medical therapy may begin with varying doses of a hormone called human chorionic gonadotropin (hCG) for 4 to 6 weeks, to facilitate the descent of the testicles. If this treatment is not effective, orchidopexy (repositioning and fixation of one or both testicles inside the scrotum) is indicated between the twelfth and eighteenth month of life to limit the aforementioned risks.

As far as people with anorchia are concerned, considering their expressed gender identity, medical treatment can begin with testosterone therapy during puberty, at progressively increasing doses, to induce the development of male secondary sexual characteristics. In adulthood, the implantation of testicular prostheses for aesthetic purposes can also be suggested. There is no unanimous consensus regarding surgery. In general, a conservative approach prevails, even though the hypothetical risk of malignancy due to any residual testicular tissue must be considered.

Bibliography
Brauner R et al. Clinical, biological and genetic analysis of anorchia in 26 boys. PLoS One. 2011; 6(8): e23292
Elamo HP et al. Genetics of cryptorchidism and testicular regression. Best Practice & Research Clinical Endocrinology & Metabolism. 2022 Jan;36(1):101619

Further Links 
Società Italiana di Andrologia e Medicina della Sessualità (SIAMS). Criptorchidismo
NHS. Undescended testicles
NIH. Genetic and Rare Diseases Information Center (GARD). Anorchia
Orphanet. Testicular regression syndrome