Complete androgen insensitivity syndrome

Physical levels and relatively low estradiol levels. People with CAIS 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 with CAIS than in men. Comorbidity exists. A few cases of breast cancer have been reported in individuals with partial androgen insensitivity syndrome. In contrast to bone health, both transdermal estradiol treatment and testosterone treatment in women with CAIS results in worsening in lipid profiles. A case report in 2009 also shows that CAIS individuals with intact testes (with endogenous hormone) are more likely to be obese. Growing evidence indicates that complete androgen receptor (AR) dysfunction disrupts systemic metabolic homeostasis and neither external nor endogenous estrogen can normalize it. AR absence is related to decrease in mature neutrophils in mice, but there is no evidence that human CAIS individuals have impaired neutrophil function. The proteome related to inflammation is predominantly inhibited in CAIS. Upregulation of IFN-β and IL-6 are reported in the blood of CAIS individuals. Leukocytes of CAIS individuals exhibit relative resistance to DNA damaging. ==Diagnosis==

CAIS is usually not suspected until the menses fail to develop at puberty, or an inguinal hernia presents during premenarche. As many as 1–2% of prepubertal girls that present with an inguinal hernia will also have CAIS. A diagnosis of CAIS or Swyer syndrome can be made in utero by comparing a karyotype obtained by amniocentesis with the external genitalia of the fetus during a prenatal ultrasound. Many infants with CAIS do not experience the normal, spontaneous neonatal testosterone surge, a fact which can be diagnostically exploited by obtaining baseline luteinizing hormone and testosterone measurements, followed by a human chorionic gonadotropin (hCG) stimulation test. The main differentials for CAIS are complete gonadal dysgenesis (Swyer syndrome) and Müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH). Both CAIS and Swyer syndrome are associated with a 46,XY karyotype, whereas MRKH is not; MRKH can thus be ruled out by checking for the presence of a Y chromosome, which can be done either by fluorescence in situ hybridization (FISH) analysis or on full karyotype. Swyer syndrome is distinguished by the presence of a uterus, poor breast development and shorter stature. The diagnosis of CAIS is confirmed when androgen receptor (AR) gene sequencing reveals a mutation, although up to 5% of individuals with CAIS do not have an AR mutation. Up until the 1990s, a CAIS diagnosis was often hidden from the affected individual, the individual's family, or both. It is current practice to disclose the genotype at the time of diagnosis, particularly when the affected individual is at least of adolescent age. If the affected individual is a child or infant, it is generally up to the parents, often in conjunction with a psychologist, to decide when to disclose the diagnosis. ==Management==

Management of AIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling. Non-consensual interventions are still often performed, although general awareness on the resulting psychological traumatization is rising. Sex assignment and sexuality Most individuals with CAIS are raised as females. At least two case studies have reported male gender identity in individuals with CAIS. Some individuals with CAIS may choose to go on testosterone HRT rather than estrogen. Research suggests that testosterone is at least as beneficial as estrogen replacement therapy and possibly improves outcomes in certain areas of well-being. If gonadectomy is performed early, then puberty must be artificially induced using gradually increasing doses of estrogen. Some choose to perform gonadectomy if and when inguinal hernia presents. Diagnostic laparoscopy and biopsy are also to be considered if imaging is ambiguous. A research in 2012 claimed that adult women with CAIS are increasingly likely to keep their gonads due to perceived benefits. Endogenous hormone profiles show very specific features that influence bone health, hormonal replacement therapy may improve bone mineral density, but it does not normalize it. For individuals with CAIS who wish to keep their gonads, a biannual screening program is proposed. It is emphasized that not all imaging abnormalities are indicative of malignancy. Research also suggest that timely intervention to reduce genotoxicity such as DNA damage, inflammation and imbalanced autophagy may promote germ cells specification and decrease the risk of germ cells tumor. It may allow to keep not only the gonads but also the potential of fertility in CAIS individuals. buccal mucosa, amnion, dura mater. Success of such methods should be determined by sexual function, and not just by vaginal length, as has been done in the past. Other complications include bladder and bowel injuries. Yearly exams are required as neovaginoplasty carries a risk of carcinoma, although carcinoma of the neovagina is uncommon. Neither neovaginoplasty nor vaginal dilation should be performed before puberty. ==Prognosis==

Challenges presented to people affected by this condition include: psychologically coming to terms with the condition, difficulties with sexual function, infertility. Long-term studies indicate that with appropriate medical and psychological treatment, those with CAIS can be satisfied with their sexual function and psychosexual development. Individuals with this condition can lead active lives and expect a normal lifespan. ==Epidemiology==

It is estimated that CAIS occurs in 1 in 20,400 to 1 in 99,000 individuals with a 46,XY karyotype. ==Nomenclature==

Historically, CAIS has been referred to in the literature under a number of other names, including testicular feminization [syndrome] (deprecated) and Morris syndrome. PAIS has also been referred to as Reifenstein syndrome, which should not be confused with CAIS. ==History==

The first definitive description of CAIS was reported in 1817. The condition became more widely known after it was reviewed and named testicular feminization by American gynecologist John McLean Morris in 1953. ==People with CAIS==

• Georgiann Davis • Seven Graham • Eden Atwood • Alicia Roth Weigel ==See also==