Androgen insensitivity syndrome (AIS) is when a person has one X and one Y sex chromosome (making them genetically male), but is resistant to androgens (male hormones). As a result, the individual has some or all of the physical characteristics of a woman, despite having the genetic makeup of a man.

The syndrome is divided into two main categories: complete and incomplete. Complete AIS results in someone who looks outwardly female. In the incomplete AIS syndrome, the degree of sexual ambiguity varies widely from individual to individual.

The syndrome is caused by various genetic mutations on the X chromosome. The mutations make a developing male baby unable to respond to androgens. (Androgens are responsible for male physical characteristics.)

If the androgen insensitivity is complete, this prevents the development of the penis and other male body parts. The child is born appearing to be a girl. The complete form of the syndrome occurs in as many as 1 in 20,000 live births.

Different degrees of androgen resistance can result in a wide variety of outward symptoms. Incomplete AIS can include other disorders, such as Reifenstein's syndrome (also known as Gilbert-Dreyfus syndrome or Lubs syndrome), which is associated with hypospadias (where the opening of the urethra is on the underside, rather than at the tip, of the penis), gynecomastia (breast development in men), and cryptorchidism (when one or both testes fail to descend into the scrotum after birth).

Also included in the broad category of incomplete AIS is infertile male syndrome, which is sometimes due to an androgen receptor disorder.

In its classic form (complete androgen resistance), the person appears to be female but has no uterus, and has sparse armpit and pubic hair. At puberty, female secondary sex characteristics (e.g., breasts) develop, but menstruation and fertility do not.

Complete AIS is rarely discovered during childhood, unless a mass is felt in the abdomen or groin that turns out to be a testicle when it is explored surgically. Most with this condition are not diagnosed until they fail to menstruate or they try to become pregnant and find that they are infertile.

Incomplete AIS, however, is often discovered during childhood because a person may have both male and female physical characteristics. Many have partial fusion of the outer vaginal lips, an enlarged clitoris, and a short, blind-ending vagina.

The individual is often diagnosed because of ambiguous genitalia. Sometimes, though, the person has primarily male characteristics and the only symptom is a low sperm count as an adult, perhaps with breast enlargement.

Signs may include:

• vagina present but no cervix or uterus
• normal female breast development
• testes in the inguinal canal, labia, or abdomen
• inguinal hernia with palpable gonad

Tests:

• Testosterone levels -- in the male range
• XY Karyotyping -- the presence of one X and one Y sex chromosome indicates male gender
• Luteinizing hormone (LH) levels -- high
• Follicle-stimulating hormone (FSH) levels -- normal
• Sonogram -- shows an absent uterus or intra-abdominal testes
• Androgen receptor studies (research setting) may confirm the syndrome

Tests which may distinguish androgen resistance from androgen deficiency (or 5-alpha reductase deficiency):

• Increased basal and hCG-induced testosterone
• Normal dihydrotestosterone

• If testicular tissue is found in the abdomen or in the inguinal canal during childhood, it might not be removed at that time. Once puberty and growth are complete, the testis may be removed because it may develop cancer like any undescended testicle. In addition, gonadoblastomas are cancers that occur almost exclusively in XY gonads of people with abnormalities of sexual differentiation.
• Estrogen replacement after puberty.
• Support of gender identity.

• Treatment and gender assignment can be a very complex issue, and must be individualized with great care.