Ambiguous genitalia may be caused by a number of conditions or abnormalities. There are chromosomal abnormalities that are related to the child’s genetic gender, but may not produce ambiguous genitalia. For example, females with Turner syndrome only have one X chromosome. In later life they will be infertile, but at birth their external genitalia appears female.

Causes of ambiguous genitalia may be grouped into the following areas:

• Hormonal and enzyme action. Much of genital development is guided by hormones and the enzymes that work with them. Numerous conditions that can cause ambiguous genitalia are related to hormones or enzymes that affect hormonal actions. Some of these include:
  
  
• Congenital adrenal hyperplasia (CAH). This is a disorder of the adrenal glands caused by an enzyme deficiency. The adrenal glands should produce the hormones cortisol and aldosterone. Without the enzymes, the glands produce male hormones called androgens. This excess of male hormones in a female baby’s system causes ambiguous genitalia. CAH is the most common cause of ambiguous genitalia in females (virilized XX). In males, CAH does not produce ambiguous genitalia, but may result in early puberty.
  
  Certain forms of CAH can be life-threatening for both genders if not recognized and treated. The missing hormones (cortisol and aldosterone) are necessary to maintain electrolyte levels and blood pressure. They must be taken as supplements for life if the adrenal glands do not produce them.
  
  
• Androgen insensitivity syndromes. In male babies, certain enzymes and receptor cells must be present to react with testosterone so the genitalia can develop. These disorders make the male fetus either completely or partially insensitive to testosterone. If testosterone cannot act, the genitals will appear as an unvirilized XY baby.
  
  
• Enzyme deficiencies in the testes. Other enzyme deficiencies also affect the formation of testosterone or affect its influence on the virilization of cells. When penile development is restricted due to an enzyme deficiency, the resulting tissue may resemble a clitoris rather than a penis.
  
  
• Maternal hormones and enzymes. The conditions in a woman’s body during pregnancy and her hormones and enzymes may affect the developing fetus and its genitalia. These changes usually affect a female fetus (virilized XX). For example, a woman may be taking androgens, which can affect the genitalia. Some women who experienced recurrent miscarriages may have been prescribed progesterone, which in excess amounts may affect the fetal genitals. The mother may have imbalances of her own hormones caused by a tumor. In addition, the absence of an enzyme in the placenta may allow more testosterone to cross the placenta and affect the fetus.
  
  
• Genetic defects. Instead of all cells having the same sex chromosomes (XX or XY), some cells may have different combinations. As a result, sometimes one gonad (ovary or testes) forms correctly and the other remains undeveloped. In cases of complete gonadal dysgenesis, neither gonad develops.
  
  
• Family history. Some of the genetic abnormalities and enzyme deficiencies associated with ambiguous genitalia are hereditary. Parents who are carriers of the gene may have children with the genetic abnormality or may pass on the gene so their children may become carriers as well.
  
  
• Environmental factors. Some cases of ambiguous genitalia may be caused by maternal or paternal exposure to chemicals. Some women whose mothers took the drug diethylstilbestrol (DES) during pregnancy developed a septum, or wall, across the vagina. Other environmental exposures may contribute to ambiguous genitalia, but their influence has not been studied.