Androgen Insensitivity Syndrome

Androgen Insensitivity Syndrome

What Is Androgen Insensitivity Syndrome?

Androgen insensitivity syndrome (AIS) is a rare condition that affects sexual development. It occurs when someone is genetically male, but their body doesn’t respond to male sex hormones called androgens. This results in a person having male sex chromosomes (one X and one Y chromosome) but not having male genitals. AIS affects males during fetal development and during puberty. AIS was previously called testicular feminization syndrome.

AIS happens due to genetic mutations, which are changes to genes that affect how they function. With AIS, the gene mutation prevents male genitals from developing in people who are genetically male. AIS almost always results in infertility.

Receiving an AIS diagnosis for yourself or your child can be difficult. The condition isn’t life-threatening, but people with AIS may struggle with gender identity or have concerns about their body image. It’s helpful to have a supportive network of healthcare providers, family and friends to talk to. Surgery can help people with AIS have genitals that match their gender identity.

Types of AIS

The different types of AIS are:

Complete androgen insensitivity syndrome (CAIS): Your body doesn’t respond to androgens at all. Your external genitals appear female, but you don’t have female sex organs (no ovaries, fallopian tubes or uterus). People with CAIS are often raised as girls with a female gender identity. Approximately 1 in 20,000 genetically male infants are born with complete androgen insensitivity syndrome.

Partial androgen insensitivity syndrome (PAIS): Your body may respond partially to androgens. Your external genitals appear neither male nor female, or a little of both. People with PAIS can be raised as boys or girls and have either a female or male identity (or both). About 1 in 99,000 genetically male infants are born with partial androgen insensitivity syndrome.

Mild androgen insensitivity syndrome (MAIS): A person’s genitals appear male, but they’re usually infertile. Some experts consider MAIS a type of PAIS.

Symptoms

What are the symptoms of androgen insensitivity syndrome?

The most common symptom across all forms of AIS is infertility. People with CAIS won’t be able to get pregnant or make their partners pregnant. They have genitals that appear female, but they don’t have female reproductive organs. It’s very rare for people with PAIS to make their partners pregnant. Even if they have a very small penis, sperm production is usually low or nonexistent.

Other signs and symptoms of complete androgen insensitivity syndrome (CAIS) include:

Abnormally tall stature for a female during puberty

No menstrual periods

Little or no pubic hair or underarm hair during puberty

Narrow or short vagina

Undescended testicles

Other signs and symptoms of partial androgen insensitivity syndrome (PAIS) can include:

Bifid scrotum (scrotum splits in two)

Large clitoris

Enlarged male breasts

Hypospadias

Labia are sealed shut

Abnormally small penis

Partially undescended testicles

Sparse body hair

What causes it?

Androgen insensitivity syndrome is a hereditary condition, meaning it’s passed down from the mother to the child. It happens when there’s a defect or abnormality in the androgen receptor (AR) gene. Androgen receptors are the cells that allow your body to respond to androgens like testosterone.

Androgens play a major role in male sexual development, supporting the development of sex organs and regulating hair growth and sex drive. The abnormal gene either blocks or partially blocks androgens. This causes a person who is genetically male to not have male genitals or other sexual traits that are typical for males.

Males who inherit the abnormal AR gene have a 1 in 4 chance of developing AIS. Females can also inherit and carry the gene, but they won’t develop AIS.

What are the complications of AIS?

Androgen insensitivity syndrome isn’t life-threatening. Still, there are possible complications from AIS, like:

Infertility: Almost all cases of AIS cause infertility due to undeveloped reproductive organs.

Risk of testicular tumors: If your testicles don’t descend into your scrotum, you’re at higher risk for testicular tumors. Most healthcare providers will recommend removing the testicles.

Psychological conditions: Living with an AIS diagnosis can be emotionally and mentally difficult. People with AIS may struggle with gender dysphoria or feel like their physical appearance doesn’t match the gender they want to be.

Diagnosis

How is androgen insensitivity syndrome diagnosed?

A healthcare provider can often diagnose PAIS (partial AIS) right after birth by looking at a baby’s genitals and noticing both male and female sexual characteristics.

But CAIS (complete AIS) or MAIS might not be evident until the age of 11 or 12, when puberty begins. This is the time when a healthcare provider might notice issues. A child with CAIS may not have menstrual periods or have any pubic hair.

A child with mild AIS might have a very small penis or develop breasts. Puberty is also when undescended testicles can bulge through an opening in the abdominal wall. Sometimes, healthcare providers discover undescended testicles if your child has surgery for an inguinal hernia.

What tests help diagnose androgen insensitivity syndrome?

Your healthcare provider will need to do tests to confirm a diagnosis. These include:

Blood tests check hormone levels, sex chromosomes and genetic abnormalities

Imaging exams, like ultrasound, can confirm the absence of female reproductive organs

If you have a biological family history of AIS, you may choose to have genetic testing if you’re considering having children. These tests can tell you if you’re a carrier of the abnormal gene.

Treatment

How is androgen insensitivity syndrome treated?

Most treatments take place after puberty. This gives your child’s body time to go through developmental changes. It also allows your child to play a more active role in their treatment decisions.

But some health experts think certain treatments, such as removal of the testicles, should happen before puberty. This reduces the risk of developing tumors in undescended testicles. Other treatments can happen after puberty.

Children raised as boys may choose to have:

Surgery to repair their male genitals, such as hypospadias repair or orchiopexy (surgery to move undescended testicles to the scrotum)

Breast reduction surgery to remove excess breast tissue

Hernia repair to close open or weakened tissue in their abdominal walls

Hormone therapy with testosterone

Children raised as girls may choose to have:

Surgery to remove male genitals or extra clitoral tissue

Nonsurgical vaginal dilation to make their vaginas deeper

Hormone therapy with estrogen

Parents and healthcare providers may decide not to assign a gender at birth. Sometimes, they wait until puberty to choose one. Or parents might want the child to choose their own.

Type of Doctor Department : An endocrinologist and a geneticist