What Happens to a Person With Androgen Insensitivity Disorder?

Medically Reviewed on 2/13/2023
Androgen Insensitivity Disorder
AIS may confuse one's gender identity and cause difficulties with social interactions.

Androgen insensitivity syndrome (AIS) or disorder is a rare genetic condition that affects the development of sexual characteristics in people with XY (male) chromosomes.

  • People with AIS are born with the genetic makeup of a man, but their bodies do not respond to male sex hormones called androgens.
  • They may have physical features that are more typical of a woman even though they have XY chromosomes.

What are the signs and symptoms of androgen insensitivity disorder?

Androgen insensitivity disorder affects a body’s ability to respond to androgens. These hormones play a key role in the development of male characteristics.

Here are a range of physical signs and symptoms of androgen insensitivity syndrome (AIS):

  • Ambiguous genitalia: People with AIS could be born with a small penis, enlarged clitoris, and underdeveloped scrotum.
  • Infertility: Affected individuals are generally unable to produce sperm, which can lead to infertility.
  • Delayed puberty: May experience delayed puberty, with little or no change in the development of secondary sexual characteristics, such as facial hair, a deep voice, or increased muscle mass.
  • Breast development: Some people with AIS may develop breasts during puberty due to the presence of estrogen in their bodies.
  • Short stature: Could be shorter than average due to a lack of androgens, which play a role in the growth of bones.
  • Disproportionate body proportions: A shorter trunk and longer legs compared to the average person due to a lack of androgens.
  • Absence of menstrual cycles: May have female genitalia but not experience menstruation due to the absence of functional ovaries.
  • Psychological effects: Confusion about one's gender identity and difficulties with social interactions.

The signs and symptoms of AIS can vary widely from person to person, and some people may have more severe symptoms than others.

What are the types of androgen insensitivity disorders?

There are three types of androgen insensitivity syndrome (AIS), which can range in severity and cause different symptoms.

  1. Complete androgen insensitivity syndrome (CAIS)
    • The most severe form of AIS. People with CAIS are born with female genitalia, but they do not have a uterus and do not menstruate. 
    • They do not develop secondary sexual characteristics, such as breasts, during puberty. Despite having a female appearance, people with CAIS do not produce eggs and get pregnant.
  2. Partial androgen insensitivity syndrome (PAIS)
    • A less severe form of AIS. People with PAIS may have some female characteristics, such as a shallow vagina or small breasts, or a combination of male and female physical characteristics.
    • They may have reduced fertility and cannot get pregnant.
  3. Mild androgen insensitivity syndrome (MAIS)
    • The mildest form of AIS. People with MAIS may have normal male genitalia and secondary sexual characteristics, but they may have reduced fertility.

The severity of AIS can vary widely, even within the same type. Some people with AIS may have very mild symptoms, while others may have more severe symptoms.

What causes androgen insensitivity disorder?

Different causes of AIS

  • Genetic mutations: The most common cause of androgen insensitivity syndrome (AIS). A mutation in the gene that codes for the androgen receptor affects the functioning of the androgen receptor. This gene produces a protein that allows cells to respond to androgens. Women who carry the genetic change will not get AIS, but each kid they have has a one in four risks of developing AIS.
  • Chromosomal abnormalities: Klinefelter’s syndrome (47, XXY) or Turner’s syndrome (45, X) is due to an abnormal number of chromosomes, which can disrupt the normal development of the reproductive organs and other physical characteristics.
  • Environmental factors: Evidence suggests that environmental factors, such as exposure to certain chemicals or medications during pregnancy, may increase the risk of AIS. However, further research is needed to confirm this.
  • Unknown causes: In some cases, the cause of AIS is unknown.

AIS is a rare condition, in which partial androgen insensitivity syndrome affects about 1 in 99,000 male babies, whereas total androgen insensitivity syndrome affects 2 to 5 per 100,000 births.

Risk factors for AIS

  • Passed down in the family: Mutations in the androgen receptor gene are passed down from parents. If a person has a family history of AIS, they could be at an increased risk of developing the condition.
  • Prenatal exposure to certain medications or chemicals: Diethylstilbestrol can disrupt normal fetal development.
  • Abnormal prenatal hormone levels: Can interfere with normal male or female sexual development.
  • Certain medical conditions: Congenital adrenal hyperplasia can disrupt normal hormone levels and increase the risk of AIS.

There could be other unidentified risk factors for the condition.

What are the treatment options for androgen insensitivity disorder?

There are several treatment options for androgen insensitivity syndrome (AIS), including hormone therapy, surgery, and counseling.

Here is a more detailed explanation of the available treatment options:

  • Hormone therapy: This treatment involves taking medications to replace the hormones that the body is unable to produce or respond to. This can include androgens (such as testosterone) to help with the development of secondary sex characteristics and estrogen to help with the development of female secondary sex characteristics.
  • Surgery: Depending on the specific symptoms and physical characteristics of an individual with AIS, surgery could be recommended to alter the genitalia to better match the person's gender identity. For example, a person with a male gender identity and AIS may undergo surgery to remove the testes and create a more typical female appearance.
  • Counseling: AIS can have significant physical, emotional, and social effects, and individuals with AIS need to receive support and guidance from mental health professionals. Counseling can help individuals with AIS manage their emotions, cope with the challenges of living with the condition, and make informed decisions about their treatment options.

The specific treatment plan for an individual with AIS will depend on their specific symptoms and needs and a combination of these or other treatment options. People must work closely with an experienced healthcare team to ensure the best possible care.

Medically Reviewed on 2/13/2023
Image Source: iStock image

Androgen Insensitivity Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK1429/

Androgen Insensitivity Syndrome. https://emedicine.medscape.com/article/924996-overview

Androgen Insensitivity Syndrome. https://www.chop.edu/conditions-diseases/androgen-insensitivity-syndrome