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Testicular Feminization (AIS)

Updated on October 7, 2012

Testicular Feminization (AIS)

Androgen insensitivity syndrome (AIS) alternatively known as testicular feminization, is an X-linked disorder which effects the sexual development. People with this syndrome are genetically males with 46,XY karyotypes, but show characteristics like feminization of the external genitalia at the time of birth, improperly developed secondary sexual characteristics at the time of puberty, lack of fertility etc. This disease is characterized by the end-organ resistance to androgens (testosterone and dihydrotestosterone). The first description of AIS was given by John Morris in 1953.

What causes Testicular Feminization or Androgen Insensitivity Syndrome?

Androgen receptor gene (AR gene), encodes for a protein known as androgen receptors. AR gene is located on the long arm of the X chromosome (ie, Xq11-12). Mutations in this gene alone are known to be the cause behind AIS. Androgens are hormones which stimulate the sexual development in males. These hormones are recognized by the androgen receptors of the cells. Proper functioning of the hormone and its receptors is together responsible for some of the vital functions in both males and females like, sex traits, distribution of hairs etc. Mutations in the AR gene hamper the proper functioning of the AR gene, due to which the cells either fail to respond or incompletely respond to androgens. The variation in the sex characteristics depends on the intensity of the insensitivity to androgens. AIS is inherited in an X-linked recessive pattern, that is, it is generally inherited (two-third of cases) from mothers who carry the mutated copy of the AR gene, on either of the two X chromosomes. As the males have a single X chromosome, presence of even a single copy of the mutated gene, is enough to cause the disease. Certain endocrine and neurological disorders also lead to defects in AR gene, leading to AIS, for example, Spinal and Bulbar Muscular Atrophy (SBMA) or Kennedy’s disease.

Types of Testicular Feminization or Androgen Insensitivity Syndrome

Androgen Insensitivity Syndrome is basically classified into two types based on the intensity of the insensitivity to androgens.

  • Complete androgen insensitivity syndrome (CIAS) – In this disease the cells of the end organs cannot use androgens at all. As a result the external genitals of the male child are similar to that of females. They show a short blind ending vagina and absence of vas deferens, seminal vesicles, epididymides and prostate. Even though external sex characteristics are similar to that of females, the child lacks uterus. As a result the child cannot menstruate like normal females and remains infertile. Breast enlargement is noticed in them by the time they attain puberty but they lack pubic and under arms hair. Children suffering from this syndrome are generally brought up as girls and are also identified as females. Internal male sex organs like testes remain undescended and abnormally located in the pelvis or abdomen. These people show scanty hair in the pubic areas and under the arms. CIAS is prevalent in a ratio of 1 out of every 20,000-64,000 male births.
  • Partial/mild androgen insensitivity syndrome (PIAS) – This problem is alternatively known as Reifenstein syndrome and during this syndrome, tissues of the body show partial sensitivity to androgens. This problem is as common as CIAS. The development of the external sex characteristics depends on the level of sensitivity. For example, having both male and female sex characteristics or having either normal female/male sex characteristics. Children suffering from this syndrome can be brought up as either girls or boys. These people are generally infertile and show breast enlargement by the time they attain puberty.

Diagnosis of Testicular Feminization or Androgen Insensitivity Syndrome

The diagnosis of AIS is based on the clinical findings and laboratory tests. The primary criteria to be ascertained during the diagnosis is the presence of 46,XY karyotype along with baseline synthesis of testosterone and testosterone precursors. During PIAS, the presence of abnormal genital organs can help in the diagnosis at the time of birth. However the diagnosis of CIAS becomes rather difficult as the external genital organs look normal. In such condition CIAS is generally recognized at the time of puberty. As the girls show normal breast development but fail to menstruate and lack pubic hairs. The family history of the X-linked inheritance is also considered during diagnosis.

Under laboratory tests, blood tests are done to test the levels of luteinizing hormone (LH) and testosterone. Imaging studies are done to detect short blind-end vagina, absence of uterus. Absence or the underdevelopment of organs like vas deferens and seminal vesicles can also be examined through ultrasound images. Molecular genetic testing of AR gene or karyotype detection is another part of the diagnostic tests.

Treatment of Testicular Feminization or Androgen Insensitivity Syndrome

There is no direct treatment available for such primary genetic defects. Patients suffering from CIAS grow up to lead normal female lives except for the fact that they are infertile and cannot menstruate. Generally after they attain puberty the testis are surgically removed as they can prove to be cancerous in the later stages. Vaginal dilatation is also carried to avoid dyspareunia. People suffering from PIAS, who show dominant female genitalia, are treated in the same manner as discussed above. However, in these individuals prepubertal gonadectomy (removal of gonads prior to puberty) is carried to avoid increasing clitoromegaly at the time of puberty. Some hormone supplements are also prescribed for patients suffering fro PIAS.


As this genetic disease is irreversible, patients need to be monitored by endocrinologists and psychiatrists. Appropriate treatment and support by doctors and family members is very essential to make these patients lead normal lives.

Source of information:

Galani A, Kitsiou-Tzeli, S. (2008).Androgen insensitivity syndrome: clinical features and molecular defects. HORMONES. 7(3): 217-229.


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