Androgen insensitivity syndrome (AIS) is when a person who is genetically male (has one X and one Y chromosome) is resistant to male hormones called androgens. As a result, the person has some or all of the physical characteristics of a woman, despite having the genetic makeup of a man.
Causes, incidence, and risk factors
Androgen insensitivity syndrome (AIS) is caused by various genetic defects on the X chromosome that make the body unable to respond to the hormones responsible for the male appearance.
The syndrome is divided into two main categories:
Complete androgen insensitivity prevents the development of the penis and other male body parts. The child born appears to be a girl. The complete form of the syndrome occurs in as many as 1 in 20,000 live births.
The degree of sexual ambiguity varies widely in persons with incomplete AIS. Incomplete AIS can include other disorders such as Reifenstein syndrome (also known as Gilbert-Dreyfus syndrome or Lubs syndrome), which is associated with breast development in men, failure of one or both testes to descend into the scrotum after birth, and hypospadias, a condition where the opening of the urethra is on the underside, rather than at the tip, of the penis.
Also included in the broad category of incomplete AIS is infertile male syndrome, which is sometimes due to an androgen receptor disorder.
A person with complete AIS appears to be female but has no uterus, and has very little armpit and pubic hair. At puberty, female secondary sex characteristics (such as breasts) develop, but menstruation and fertility do not.
Persons with incomplete AIS may have both male and female physical characteristics. Many have partial closing of the outer vaginal lips, an enlarged clitoris, and a short vagina.
Testes in the abdomen or other unusual places in the body
Signs and tests
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 people with this condition are not diagnosed until they fail to menstruate or have difficulties becoming pregnant.
Incomplete AIS, however, is often discovered during childhood because the person may have both male and female physical characteristics.
Tests used to diagnose this condition may include:
Blood work to check levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)
Genetic testing (karyotyping)
Other blood tests may be done to help tell the difference between AIS and androgen deficiency.
Unusually located testicular tissue may not be removed until a child completes puberty and growth is complete. At this time, the testis may be removed because they can develop cancer like any undescended testicle.
Estrogen replacement is prescribed after puberty.
Treatment and gender assignment can be a very complex issue, and must be individualized with great care.
The outlook for complete AIS is good if at-risk testicular tissue is removed at the proper time. The outlook for incomplete AIS depends on the presence and severity of ambiguous genitalia.
Complications include testicular cancer, infertility, and complex psychosocial issues.
Calling your health care provider
Call your health care provider if you or your child have signs or symptoms of the syndrome.
Wysolmerski JJ. Insogna KL. The parathyroid glands, hypercalcemia, and hypocalcemia. In: Kronenberg HM, Schlomo M, Polansky KS, Larsen PR, eds. Williams Textbook of Endocrinology. 11th ed. St. Louis, Mo: WB Saunders; 2008:chap 266.
Bringhurst FR, Demay MB, Kronenberg HM. Disorders of mineral metabolism. In: Kronenberg HM, Schlomo M, Polansky KS, Larsen PR, eds. Williams Textbook of Endocrinology. 11th ed. St. Louis, Mo: WB Saunders; 2008:chap 27.
Ari S. Eckman, MD, Chief, Division of Endocrinology, Diabetes and Metabolism, Trinitas Regional Medical Center, Elizabeth, NJ. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.