Defects in the androgen receptor gene located on the X chromosome include absence of the gene that encodes for the androgen receptor and abnormalities in the binding domains of the receptor. Androgen receptor deficits are diverse and may result from diminished receptor function or concentration. The diversity of androgen receptor mutations may be related to diversity in phenotype. More than 250 extremely diverse mutations are described, with amino acid substitution being by far the most common (66,67). Postreceptor defects can exist (68). Total serum testosterone concentration is in the range of normal males. Because antim¨ullerian hormone is present and functions normally in these patients, internal female (m¨ullerian) structures such as a uterus, vagina, and fallopian tubes are absent. Testes rather than ovaries are present in the abdomen or in inguinal hernias because of the presence of normally functioning genes on the Y chromosome. Patients have a blind vaginal pouch and scant or absent axillary and pubic hair. These patients experience abundant breast development at puberty; however, the nipples are immature and the areolae are pale. Testosterone is not present during development to suppress the formation of breast tissues; at puberty, the conversion of testosterone to estrogen stimulates breast growth. Patients are unusually tall with eunuchoidal tendency (long arms with big hands and feet).
True Hermaphroditism True hermaphroditism is a rare condition that should be considered as a possible cause of amenorrhea. Both male and female gonadal tissues are present in these patients, in whom XX, XY, and mosaic genotypes are found. Two-thirds of the patients menstruate, but menstruation was never reported in XY genotypes. The external genitalia usually are ambiguous, and breast development frequently occurs in these individuals. Fifteen percent of XX true hermaphrodites have SRY translocations, and another 10% have Y chromosomal mosaicism within the gonad (17).
Evaluation of Women with Amenorrhea, Normal Secondary Sexual Characteristics, and Suspected Anatomic Abnormalities
Figure 30.2 A: A well-developed patient with complete androgen insensitivity. Note the characteristic paucity of pubic hair and well-developed breasts. (From Yen SSC, Jaffe RB. Reproductive endocrinology. 3rd ed. Philadelphia, PA: WB Saunders, 1991:497, with permission.) B: Another patient with androgen insensitivity syndrome with a contrasting thin body hiatus. This is a 17-year-old twin 46,XY. (From Jones HW Jr, Scott WW. Hermaphrodism, genital anomalies, and related endocrine disorders. 2nd ed. Baltimore, MD: Williams & Wilkins, 1971, with permission.)
Most congenital abnormalities can be diagnosed by physical examination: 1.
An imperforate hymen is diagnosed by the presence of a bulging membrane that distends during Valsalva maneuver. Ultrasonography or MRI is useful to identify the m¨ullerian anomaly when the abnormality cannot be found by physical examination. The patient should be examined for skeletal malformations and assessed with intravenous pyelography or renal ultrasound to detect concomitant renal abnormalities. These abnormalities occur less frequently than in m¨ullerian agenesis (63).
2.
It is difficult to differentiate a transverse septum or complete absence of the cervix and uterus in a female from a blind vaginal pouch in a male pseudohermaphrodite by examination alone. Androgen insensitivity is likely when pubic and axillary hair is absent. To confirm the diagnosis, a karyotype determination should be performed to see whether a Y chromosome is present. In some patients, the defect in the androgen receptor is not complete and virilization occurs.
3.