Androgen Insensitivity

Androgen insensitivity is a rare genetic condition that blocks the body from using male hormones (androgens) during fetal growth and after birth. Because the fetal tissue is insensitive to male hormones, the masculinizing that should occur in a genetic male cannot happen. These children develop as normal females, but are missing internal female reproductive organs.

Androgen insensitivity is a genetic mutation that can be inherited from the mother or can happen as a spontaneous genetic mutation at conception. An estimated 1 in 65,000 female infants (with the male karyotype XY) are born with androgen insensitivity.

There is another form of the condition called partial androgen sensitivity, in which a child will have ambiguous genitalia.

The gene for androgen sensitivity is on the X chromosome, so genetic females carrying the gene won't appear affected because they have another normal X chromosome. Girls who are carriers may have thinner pubic hair and less normal teenage acne. They also have a 50 percent chance of passing the mutated gene on in each pregnancy.

Possible symptoms of androgen sensitivity include:

• Absence of a menstrual cycle
• Sparse or absent pubic and armpit hair
• Hernias or lumps in the groin or abdomen, that are actually testes
• A short vagina
• Ambiguous genitalia in a child with partial androgen insensitivity

Girls and women with androgen insensitivity have normal external genitalia, namely, a lower vagina, labia, clitoris, and urethra. Girls with androgen insensitivity look like normal females and go through puberty and normal breast development, but because their bodies cannot use testosterone, they will have scant or no pubic and armpit hair. Inside her body, the internal sexual organs don't form normally. In fetal development, her fetal testes produced something called mullerian inhibiting substance, which prevented the growth of the upper vagina, cervix, and uterus.

Girls with androgen insensitivity have a Y chromosome, which causes testes to grow. So, she will have testes that may appear as hernias or lumps in the groin or abdomen. These will need to be removed to prevent cancer.

Androgen insensitivity is a genetic mutation on the X chromosome that can be inherited from the mother or happen as a spontaneous genetic change at conception. This mutation prevents the body tissue from using male hormones (androgens) during fetal development and after birth. This will interfere with gender development, because, in early fetal life, the potentially male (XY) and female (XX) fetuses are identical and require androgens to develop into a male.

The fetal tissue cells are missing the androgen receptor, so when androgens are released during development in a genetically male fetus, the cells cannot respond to the androgens — almost like trying to fit a house key into the wrong door. Masculinization won't occur, so the baby will develop into a female because estrogen is present.

Complete androgen insensitivity is usually not diagnosed before puberty, unless a lump is felt in the groin or abdomen, and it turns out to be a testicle during surgery. Usually, androgen insensitivity is diagnosed only after a young woman discovers that she hasn't started menstruation.

Partial androgen insensitivity is usually discovered earlier in life because the baby will have ambiguous genitalia.

A physician may use the following diagnostic tests to diagnose androgen insensitivity:

• Genetic testing
• Blood work to check the levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
• Pelvic ultrasound

Girls with androgen insensitivity have a Y chromosome, which causes testes to grow. So, your daughter will have testes in her abdomen or groin that may appear as hernias. Treatment will involve surgically removing the testes during childhood or after puberty, because they are at risk of forming a germ line tumor.

Once the testes are removed, your daughter will need hormone replacement therapy with estrogen. She won't need progesterone because she doesn't have a uterus.

Since your daughter doesn't have an upper vagina, her vagina may be short. She may need surgery to lengthen it, but every girl is different and sexual intercourse also naturally grows the vagina. Before she becomes sexually active, she can use a vaginal dilator to gain some length. Your daughter may find the following guide from the Center for Young Women's Health helpful: Instructions on the Use of Vaginal Dilators.

The outlook for a child with androgen insensitivity is good if at-risk testicle tissue is removed at the proper time. Women with androgen insensitivity won't be able to give birth to a child, because they don't have internal reproductive organs.

At the Center for Congenital Anomalies of the Reproductive Tract, we understand the needs of a girl with androgen insensitivity. The center offers many forms of support to you, from immediate testing to expert, long-term medical care. We will work with your daughter to decide on the best time-line for her treatment.

Boston Children's is also home to the Gender Management Service (GeMS) Clinic, which treats the medical and psychosocial issues of infants, children, adolescents, and young adults with disorders of sexual differentiation.