Physical Persons with a<unk>  androgen insensitivity have a typical female external phenotype, despite having a 46,XY karyotype. Individuals with<unk>  (grades 6 and 7 on the Quigley scale) are born phenotypically female, without any signs of genital masculinization, despite having a 46,XY karyotype. Symptoms of<unk>  do not appear until puberty, which may be slightly delayed, but is otherwise normal except for absent menses and diminished or absent secondary terminal hair. Axillary hair (i.e. armpit hair) fails to develop in one third of all cases. External genitalia is normal, although the labia and clitoris are sometimes underdeveloped. Vaginal depth varies widely for<unk>  women, but is typically shorter than unaffected women; one study of eight women with<unk>  measured the average vaginal depth to be 5.9 cm (vs. 11.1 ± 1.0 cm for unaffected women ). In some extreme cases, the vagina has been reported to be aplastic (resembling a "dimple"), though the exact incidence of this is unknown. The gonads in these women are not ovaries, but instead, are testes; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. They may be located intra-abdominally, at the internal inguinal ring, or may herniate into the labia majora, often leading to the discovery of the condition. Testes in affected women have been found to be atrophic upon gonadectomy. Testosterone produced by the testes cannot be directly used due to the mutant androgen receptor that characterizes<unk> ; instead, it is aromatized into estrogen, which effectively feminizes the body and accounts for the normal female phenotype observed in<unk> . Immature sperm cells in the testes do not mature past an early stage, as sensitivity to androgens is required in order for spermatogenesis to<unk> . Germ cell malignancy risk, once thought to be relatively high, is now thought to be approximately 2%. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically absent, but will develop at least partially in approximately 30% of cases, depending on which mutation is causing the<unk> . The prostate, like the external male genitalia, cannot masculinize in the absence of androgen receptor function, and thus remains in the female form. The Müllerian system (the fallopian tubes, uterus, and upper portion of the vagina) typically regresses due to the presence of anti-Müllerian hormone originating from the Sertoli cells of the testes. These women are thus born without fallopian tubes, a cervix, or a uterus, and the vagina ends "blindly" in a pouch. Müllerian regression does not fully<unk>  in approximately one third of all cases, resulting in Müllerian "remnants". Although rare, a few cases of women with<unk>  and fully developed Müllerian structures have been reported. In one exceptional case, a 22-year-old with<unk>  was found to have a normal cervix, uterus, and fallopian tubes. In an unrelated case, a fully developed uterus was found in a 22-year-old adult with<unk> . Other subtle differences that have been reported include slightly longer limbs and larger hands and feet due to a proportionally greater stature than unaffected women, larger teeth, minimal or no acne, well developed breasts, and a greater incidence of meibomian gland dysfunction (i.e. dry eye syndromes and light sensitivity). Endocrine Hormone levels have been reported in gonadally intact<unk>  women in a number of studies. Hormone levels are similar to those of males, including high testosterone levels and relatively low estradiol levels. However, luteinizing hormone (LH) levels are elevated while sex hormone-binding globulin (SHBG) levels are more consistent with those of females. Women with<unk>  have low levels of progesterone similarly to males. The production rates of testosterone, estradiol, and estrone have been reported to be higher in gonadally intact<unk>  women than in men. Comorbidity Histopathology of testicular tissue showing immature germ cells and spermatagonia with decreased tubular diameter. Scattered groups of Leydig cells appearing immature. All forms of androgen insensitivity, including<unk> , are associated with infertility, though exceptions have been reported for both the mild and partial forms.<unk>  is associated with a decreased bone mineral density. Some have hypothesized that the decreased bone mineral density observed in women with<unk>  is related to the timing of gonadectomy and inadequate estrogen supplementation. However, recent studies show that bone mineral density is similar whether gonadectomy occurs before or after puberty, and is decreased despite estrogen supplementation, leading some to hypothesize that the deficiency is directly attributable to the role of androgens in bone mineralization.<unk>  is also associated with an increased risk for gonadal tumors (e.g. germ cell malignancy) in adulthood if gonadectomy is not performed. The risk of malignant germ cell tumors in women with<unk>  increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. The incidence of gonadal tumors in childhood is thought to be relatively low; a recent review of the medical literature found that only three cases of malignant germ cell tumors in prepubescent girls have been reported in association with<unk>  in the last 100 years. Some have estimated the incidence of germ cell malignancy to be as low as 0.8% before puberty. Vaginal hypoplasia, a relatively frequent finding in<unk>  and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia. At least one study indicates that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis. Lifespan is not thought to be affected by AIS. Despite the well-developed breasts in<unk>  women, and for reasons that are not well-understood, breast cancer has never been reported in<unk>  women and does not seem to occur or occurs only rarely. Only a case report of juvenile fibroadenoma exists. A few cases of breast cancer have been reported in individuals with partial androgen insensitivity syndrome however.
Complete androgen insensitivity syndrome
Mild androgen insensitivity syndrome
Partial androgen insensitivity syndrome
Androgen insensitivity syndrome
Estrogen insensitivity syndrome
Gonadotropin-releasing hormone insensitivity
Kallmann syndrome
Klinefelter syndrome