Androgen insensitivity syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 3, 2017
StartDiseasesAndrogen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is a rare medical condition that dramatically affects the development of a child’s reproductive organs and genitals. While most people born with this condition are unable to have children, they are able to live otherwise healthy lives. Although treatable, people affected by this condition benefit from psychological support.


Definition & Facts

AIS is a genetic disorder that children are born with (that is, it's a congenital disorder). At birth, a child with AIS is genetically male. However, the external appearance of the genitals varies. They may appear entirely female or somewhere between the two sexes.

There are several types of AIS, depending on how much of the androgens the body is able to use. Complete androgen insensitivity syndrome (CAIS) is characterized by entirely female genitals, while partial androgen insensitivity syndrome (PAIS) occurs when the genitals fall somewhere in between.

PAIS occurs when androgens still play a major role in sexual development, while CAIS is not affected by androgens. PAIS is typically noticed at birth, but CAIS can be difficult to see and diagnose until puberty, when the menstrual cycle does not begin. CAIS is seen in 2 to 5 out of 100,000 people, and PAIS is believed to occur at a similar frequency. 

Symptoms & Complaints

Some symptoms can be observed from the moment of birth, such as developmentally abnormal genitals or those that do not appear fully male. A person with CAIS will externally appear to be female, but internally will not have a uterus. At puberty, female sex characteristics, such as breasts will develop. However, very little armpit and pubic hair will grow. Because the menstrual cycle will never begin, the person will not become fertile or reproduce.

People afflicted by PAIS may display both female and male physical characteristics. Testes may grow inside the abdominal cavity. Some PAIS patients display a partial closing of the vagina (making sexual intercourse difficult), a lack of cervix, and/or an enlarged clitoris.

Hypospadias is another symptom, which occurs when the hole ejecting urine develops on the underside of the penis. While most babies born with PAIS are raised as males, some are brought up as female as well. Potential complications include infertility, testicular cancer, and both psychological problems and social issues.


AIS is caused by genetic mutations on the X chromosome, which is usually passed on from the mother. Since women have two X chromosomes, the normal one is capable for making up for the faults of the other. Females born with one faulty X chromosome will not have AIS. They develop normally and are able to produce children.

Although they will not develop AIS themselves, mothers carrying the genetic defect have a one in four chance of passing it on to their male child, who will develop AIS. Males are only born with one X chromosome. If their mother has a damaged X chromosome, they are susceptible to inheriting the defective gene. The Y chromosome from the father cannot make up for this, amd the child will develop AIS.

Male sex hormones are produced by the testicles and control male development, such as penis growth and the testicles dropping into the scrotum. The genetic defect present in AIS prevents the body from responding to androgens properly. 

Diagnosis & Tests

Although the disease can be diagnosed soon after birth, it may not be completely noticeable until the child reaches the age of change. Because the body’s major hormonal changes occur at puberty, this is the most common time for AIS to be noticed. PAIS is more likely to be discovered during childhood because of the appearance of both male and female traits. CAIS is rarely diagnosed until the child presents a major warning sign, such as lack of menstrual period or the growth of a testicle in the abdomen or groin.

Doctors may use several types of test to diagnose the condition. If the child’s main symptom is lack of a menstrual cycle, doctors may conduct blood tests to check the levels of three crucial hormones: testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH).

Pelvic ultrasounds can also be done to determine which reproductive organs the person has internally. This procedure will detect a lack of ovaries or testicles that are hidden in the abdominal cavity. A genetic test called a karyotype may be done to examine the genetic makeup, which will show if the person has a damaged X chromosome or if the genetic sex differs from the physical appearance. 

Treatment & Therapy

Treatments for AIS include various reconstructive surgeries as well as hormone therapy. It is a psychologically and socially fraught issue because of the complexities of gender assignment.

The testes may be removed from the abdominal cavity if they fail to drop into the scrotum after birth. Testes left in the abdominal cavity can become cancerous in adulthood. The removal surgery is typically conducted after puberty. If, however, the baby is born with a scrotum, the testicles can be surgically lowered within the first year. Males who develop breasts can have them removed.

Estrogen replacement therapy can be prescribed around the time of puberty for children raised as female, while male children will require androgens in order to develop masculine traits. Psychological counseling is also highly recommended due to the negative mental effects that this diagnosis can have on a person. 

Prevention & Prophylaxis

Unfortunately, there are currently no known ways to prevent AIS. Those born with this condition can lead healthy long lives. Seeking the psychological support via psychotherapy, support groups, and other means may help individuals and families cope with the considerable emotional stresses of this condition.