complete androgen insensitivity syndrome

File:Complete androgen insensitivity syndrome.jpg

Individuals with complete androgen insensitivity syndrome (grades 6 and 7 on the Quigley scale) are born with an external female phenotype, without any signs of genital masculinization, despite having a 46,XY karyotype. CAIS is usually recognized at 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. The vulva is normal, although the labia and clitoris are sometimes underdeveloped. Vaginal depth varies widely for CAIS, but is typically shorter than normal; one study of eight people with CAIS 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 people with CAIS 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 those affected 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 CAIS; instead, it is aromatized into estrogen, which effectively feminizes the body and accounts for the normal female phenotype observed in CAIS. However, up to 5% of individuals with CAIS do not have an AR mutation. The receptor in question is encoded by the AR gene located on the X chromosome at Xq11–12. At least 15 different mutations were known in 2003, and they are all recessive, which makes the disease follow X-linked recessive inheritance.

Immature sperm cells in the testes do not mature past an early stage, as sensitivity to androgens is required in order for spermatogenesis to complete. 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 CAIS. 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 typically regresses the same way it does in unaffected male fetuses due to anti-Müllerian hormone originating from the Sertoli cells of the testes. Thus, people with CAIS, despite having a vagina due to androgen insensitivity, are born without fallopian tubes, a cervix, or a uterus, and the vagina ends "blindly" in a pouch. Müllerian regression does not fully complete in some cases of CAIS, resulting in Müllerian "remnants". Although rare, a few cases of people diagnosed with CAIS and having Müllerian structures have been reported. In one exceptional case, a 22-year-old with CAIS was found to have a cervix, uterus, and fallopian tubes. In an unrelated case, almost fully developed uterus was found in a 22-year-old adult with CAIS.

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, a greater incidence of meibomian gland dysfunction (i.e. dry eye syndromes and light sensitivity), and dry skin and hair resulting from a lack of sebum production.{{Cite journal |title=The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity |date=1993 |doi=10.1210/jcem.76.2.8381804 |url=https://academic.oup.com/jcem/article-abstract/76/2/524/2651493 |access-date=2023-08-30 |last1=Imperato-Mcginley |first1=J. |last2=Gautier |first2=T. |last3=Cai |first3=L. Q. |last4=Yee |first4=B. |last5=Epstein |first5=J. |last6=Pochi |first6=P. |journal=The Journal of Clinical Endocrinology & Metabolism |volume=76 |issue=2 |pages=524–528 |pmid=8381804 }}

Hormone levels have been reported in gonadally intact people with CAIS in a number of studies.{{cite journal | vauthors = Bertelloni S, Dati E, Baroncelli GI, Hiort O | title = Hormonal management of complete androgen insensitivity syndrome from adolescence onward | journal = Horm Res Paediatr | volume = 76 | issue = 6 | pages = 428–33 | date = 2011 | pmid = 22156544 | doi = 10.1159/000334162 | s2cid = 35239423 }}{{cite journal | vauthors = King TF, Wat WZ, Creighton SM, Conway GS | title = Bone mineral density in complete androgen insensitivity syndrome and the timing of gonadectomy | journal = Clin. Endocrinol. (Oxf) | volume = 87 | issue = 2 | pages = 136–140 | date = August 2017 | pmid = 28493277 | doi = 10.1111/cen.13368 | s2cid = 4877830 }} 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.{{cite journal | vauthors = Heyns W | title = The steroid-binding beta-globulin of human plasma | journal = Adv Steroid Biochem Pharmacol | volume = 6 | pages = 59–79 | date = 1977 | pmid = 339697 }} People with CAIS have low levels of progesterone similarly to males.{{cite book|author=Antonio R. Gargiulo|title=Yen & Jaffe's Reproductive Endocrinology E-Book: Physiology, Pathophysiology, and Clinical Management|url=https://books.google.com/books?id=67ZEDwAAQBAJ&pg=PA250|date=23 December 2017|publisher=Elsevier Health Sciences|isbn=978-0-323-58232-2|pages=250–}}{{cite journal | vauthors = Schindler AE, Freidrich E, Keller E, Joel EW, Jaeger-Whitegiver ER | title = In vivo und in vitro Untersuchungen bei Patienten mit testikulärer Feminisierung | trans-title = In-vivo and in-vitro studies of patients with testicular feminization | language = de | journal = Arch Gynakol | volume = 219 | issue = 1–4 | pages = 584 | date = November 1975 | pmid = 1243499 | doi = 10.1007/BF00669260 | s2cid = 41243904 }}{{cite journal | vauthors = Blumenthal NJ, Lubbe F, Harnekar AB, Adno A | title = Complete androgen insensitivity | journal = S. Afr. Med. J. | volume = 62 | issue = 22 | pages = 812–4 | date = November 1982 | pmid = 7147110 | url = https://journals.co.za/content/m_samj/62/22/AJA20785135_7659}} The production rates of testosterone, estradiol, and estrone have been reported to be higher in gonadally intact with CAIS than in men.{{cite book|author1=Adam H. Balen|author2=Sarah M. Creighton|author3=Melanie C. Davies|author4=Richard Stanhope |author5=Jane MacDougall|title=Paediatric and Adolescent Gynaecology: A Multidisciplinary Approach|url=https://books.google.com/books?id=Ne84QOalSe4C&pg=PA282|date=April 2004|publisher=Cambridge University Press|isbn=978-0-521-80961-0|pages=282–}}{{cite journal | vauthors = Soule SG, Conway G, Prelevic GM, Prentice M, Ginsburg J, Jacobs HS | title = Osteopenia as a feature of the androgen insensitivity syndrome | journal = Clin. Endocrinol. (Oxf) | volume = 43 | issue = 6 | pages = 671–5 | date = December 1995 | pmid = 8736267 | doi = 10.1111/j.1365-2265.1995.tb00533.x | s2cid = 23119343 }}

{{Hormone levels in gonadally intact adolescent and adult females with complete androgen insensitivity syndrome}}

File:Histopathology of androgen insensitivity.jpg

All forms of androgen insensitivity, including CAIS, are associated with infertility, though exceptions have been reported for both the mild and partial forms.

CAIS is associated with a decreased bone mineral density. Some have hypothesized that the decreased bone mineral density observed in women with CAIS 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.

CAIS 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 CAIS 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 CAIS 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 CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.

At least one study indicates that individuals with a DSD 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 CAIS women, and for reasons that are not well-understood, breast cancer has never been reported in CAIS women and does not seem to occur or occurs only rarely.{{cite journal | vauthors = Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J | title = Androgen insensitivity syndrome | journal = Lancet | volume = 380 | issue = 9851 | pages = 1419–28 | date = October 2012 | pmid = 22698698 | doi = 10.1016/S0140-6736(12)60071-3 | s2cid = 1602036 | url = https://ueaeprints.uea.ac.uk/id/eprint/63154/1/Hughes_I.A._Davies_J._Pasterski_V._Mastroyannopoulou_K._MacDougall_J._2012_._Androgen_insensitivity_syndrome_AIS_..pdf}}{{cite journal | vauthors = Tiefenbacher K, Daxenbichler G | title = The Role of Androgens in Normal and Malignant Breast Tissue | journal = Breast Care (Basel) | volume = 3 | issue = 5 | pages = 325–331 | date = 2008 | pmid = 20824027 | pmc = 2931104 | doi = 10.1159/000158055 }}{{cite book|author1=Charles G. D. Brook|author2=Peter Clayton|author3=Rosalind Brown|title=Brook's Clinical Pediatric Endocrinology|url=https://books.google.com/books?id=cLgTCCqVESYC&pg=PA200|date=22 September 2011|publisher=John Wiley & Sons|isbn=978-1-4443-1673-5|pages=200–}}{{cite book|author1=Adam H. Balen|author2=Sarah M. Creighton|author3=Melanie C. Davies|author4=Jane MacDougall |author5=Richard Stanhope|title=Paediatric and Adolescent Gynaecology: A Multidisciplinary Approach|url=https://books.google.com/books?id=pCUgAwAAQBAJ&pg=PA284|date=1 April 2004|publisher=Cambridge University Press|isbn=978-1-107-32018-5|pages=284, 287}}{{cite book|author1=Shlomo Melmed|author2=Kenneth S. Polonsky|author3=P. Reed Larsen|author4=Henry M. Kronenberg|title=Williams Textbook of Endocrinology E-Book|url=https://books.google.com/books?id=nbg1QOAObicC&pg=PA909|date=12 May 2011|publisher=Elsevier Health Sciences|isbn=978-1-4377-3600-7|pages=909–}}{{cite journal | vauthors = Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA | title = Androgen insensitivity syndrome | journal = Best Pract. Res. Clin. Endocrinol. Metab. | volume = 29 | issue = 4 | pages = 569–80 | date = August 2015 | pmid = 26303084 | doi = 10.1016/j.beem.2015.04.005 }} Only a case report of juvenile fibroadenoma exists.{{cite journal | vauthors = Davis SE, Wallace AM | title = A 19 year old with complete androgen insensitivity syndrome and juvenile fibroadenoma of the breast | journal = Breast J | volume = 7 | issue = 6 | pages = 430–3 | date = 2001 | pmid = 11843857 | doi = 10.1046/j.1524-4741.2001.07610.x | s2cid = 22116213 | doi-access = free }} A few cases of breast cancer have been reported in individuals with partial androgen insensitivity syndrome however.{{cite book|author1=Charles G. D. Brook|author2=Mehul T. Dattani|title=Handbook of Clinical Pediatric Endocrinology|url=https://books.google.com/books?id=uje5vZ8hBlwC&pg=PA54|date=16 February 2012|publisher=John Wiley & Sons|isbn=978-1-119-96813-9|pages=54–}}{{cite journal | vauthors = Hoefgen HR, Merritt DF | title = Invasive Ductal Carcinoma in a 46,XY Partial Androgen Insensitivity Syndrome Patient on Hormone Therapy | journal = J Pediatr Adolesc Gynecol | volume = 28 | issue = 4 | pages = e95–7 | date = August 2015 | pmid = 26024935 | doi = 10.1016/j.jpag.2014.08.005 }}

{{Main|Androgen insensitivity syndrome#Diagnosis|l1=Diagnosis of androgen insensitivity syndrome}}

File:Complete androgen insensitivity presenting with inguinal hernia.jpg

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 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.{{Cite journal| volume = 17| issue = 2| last = Jones| first = Tiffany| title = Intersex and Families: Supporting Family Members With Intersex Variations| url = http://digitalcommons.library.tmc.edu/jfs/vol17/iss2/8 | journal = Journal of Family Strengths| date = 2017| doi = 10.58464/2168-670X.1345| doi-access = free}}

Most individuals with CAIS are raised as females. They are born with an external phenotype of a typical female and are thought to be usually heterosexual with a female gender identity; however, some research has suggested that individuals with CAIS are more likely to have more variable gender outcomes and a non-primarily heterosexual sexual orientation than relatively similar control groups of those with MRKH syndrome and PCOS, contradicting this belief.{{Cite journal |last1=Brunner |first1=Franziska |last2=Fliegner |first2=Maike |last3=Krupp |first3=Kerstin |last4=Rall |first4=Katharina |last5=Brucker |first5=Sara |last6=Richter-Appelt |first6=Hertha |date=2016 |title=Gender Role, Gender Identity and Sexual Orientation in CAIS ("XY-Women") Compared With Subfertile and Infertile 46,XX Women |url=https://pubmed.ncbi.nlm.nih.gov/26133743/ |journal=Journal of Sex Research |volume=53 |issue=1 |pages=109–124 |doi=10.1080/00224499.2014.1002124 |issn=1559-8519 |pmid=26133743}} At least two case studies have reported male gender identity in individuals with CAIS.

File:Results of vaginal lengthening by pressure dilation methods.jpg

Most cases of vaginal hypoplasia associated with CAIS can be corrected using non-surgical pressure dilation methods. The elastic nature of vaginal tissue, as demonstrated by its ability to accommodate the differences in size between a tampon, a penis, and a baby's head, make dilation possible even in cases when the vaginal depth is significantly compromised. Treatment compliance is thought to be critical to achieve satisfactory results. Dilation can also be achieved via the Vecchietti procedure, which stretches vaginal tissues into a functional vagina using a traction device that is anchored to the abdominal wall, subperitoneal sutures, and a mold that is placed against the vaginal dimple. Vaginal stretching occurs by increasing the tension on the sutures, which is performed daily. The non-operative pressure dilation method is currently recommended as the first choice, since it is non-invasive, and highly successful. Vaginal dilation should not be performed before puberty.

While it was often recommended that women with CAIS eventually undergo gonadectomy to mitigate cancer risk, there are differing opinions regarding the necessity and timing of gonadectomy. The risk of malignant germ cell tumors with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. However, only three cases of malignant germ cell tumors in prepubescent girls with CAIS have been reported in the last 100 years. The youngest of these children was 14 years old. Individuals with CAIS naturally go through puberty via the aromatization of testosterone into estrogens. Therefore, removal of the gonads will result in an individual requiring hormone replacement therapy. Gonadectomy is generally not recommended before puberty to allow for puberty to occur spontaneously.{{cite web|url=https://www.ohchr.org/sites/default/files/Documents/Issues/Youth/StopIGM.pdf|title=Intersex Genital Mutilation, Intersex Youth and Human Rights}}{{cite journal | vauthors = Carpenter M | title = Intersex Variations, Human Rights, and the International Classification of Diseases | journal = Health and Human Rights | volume = 20 | issue = 2 | pages = 205–214 | date = December 2018 | pmid = 30568414 | pmc = 6293350 }}{{cite journal | vauthors = Greenberg JA | title = Legal, ethical, and human rights considerations for physicians treating children with atypical or ambiguous genitalia | journal = Seminars in Perinatology | volume = 41 | issue = 4 | pages = 252–255 | date = June 2017 | pmid = 28478089 | doi = 10.1053/j.semperi.2017.03.012 }} 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.{{Cite journal|title=Hormone replacement treatment choices in complete androgen insensitivity syndrome: an audit of an adult clinic - PMC|date=2017 |pmc=5527352 |last1=Ko |first1=J. K. |last2=King |first2=T. F. |last3=Williams |first3=L. |last4=Creighton |first4=S. M. |last5=Conway |first5=G. S. |journal=Endocrine Connections |volume=6 |issue=6 |pages=375–379 |doi=10.1530/EC-17-0083 |pmid=28615185 }}

If gonadectomy is performed early, then puberty must be artificially induced using gradually increasing doses of estrogen. If gonadectomy is performed late, then puberty will occur on its own, due to the aromatization of testosterone into estrogen. At least one organization, the Australasian Paediatric Endocrine Group, classifies the cancer risk associated with CAIS as low enough to recommend against gonadectomy, although it warns that the cancer risk is still elevated above the general population, and that ongoing cancer monitoring is essential.[http://www.aph.gov.au/DocumentStore.ashx?id=aafe43f3-c6a2-4525-ad16-15e4210ee0ac&subId=16191 Submission 88 to the Australian Senate inquiry on the involuntary or coerced sterilisation of people with disabilities in Australia], Australasian Paediatric Endocrine Group (APEG), 27 June 2013 Some choose to perform gonadectomy if and when inguinal hernia presents. Estrogen replacement therapy is critical to minimize bone mineral density deficiencies later in life.

Some individuals with CAIS may choose to retain their gonads. If this is the case, annual imaging of the gonads via MRI or ultrasound is recommended in order to monitor for signs of malignancy. {{Cite journal |last1=Weidler |first1=Erica M. |last2=Linnaus |first2=Maria E. |last3=Baratz |first3=Arlene B. |last4=Goncalves |first4=Luis F. |last5=Bailey |first5=Smita |last6=Hernandez |first6=S. Janett |last7=Gomez-Lobo |first7=Veronica |last8=van Leeuwen |first8=Kathleen |date=December 2019 |title=A Management Protocol for Gonad Preservation in Patients with Androgen Insensitivity Syndrome |journal=Journal of Pediatric and Adolescent Gynecology |volume=32 |issue=6 |pages=605–611 |doi=10.1016/j.jpag.2019.06.005 |issn=1873-4332 |pmc=6917890 |pmid=31233832}} Diagnostic laparoscopy and biopsy are also to be considered if imaging is ambiguous.

Some have hypothesized that supraphysiological levels of estrogen may reduce the diminished bone mineral density associated with CAIS. Data has been published that suggests affected women who were not compliant with estrogen replacement therapy, or who had a lapse in estrogen replacement, experienced a more significant loss of bone mineral density. Progestin replacement therapy is usually seldom initiated as well. Androgen replacement has been reported to increase a sense of well-being in gonadectomized people with CAIS, although the mechanism by which this benefit is achieved is not well understood.

It is no longer common practice to hide a diagnosis of CAIS from the affected individual or her family. Parents of children with CAIS need considerable support in planning and implementing disclosure for their child once the diagnosis has been established. For parents with young children, information disclosure is an ongoing, collaborative process requiring an individualized approach that evolves in concordance with the child's cognitive and psychological development. In all cases, the assistance of a psychologist experienced in the subject is recommended.

File:Inflatable vaginal expander.jpg

File:ZSI 200 NS Vaginal Expander in Vagina.jpg

Many surgical procedures have been developed to create a neovagina, but none of them are ideal. Surgical intervention should only be considered after non-surgical pressure dilation methods have failed to produce a satisfactory result. Neovaginoplasty can be performed using skin grafts, a segment of bowel, ileum, peritoneum, an absorbable adhesion barrier (Intercede, made by Johnson & Johnson),{{cite journal |vauthors=Motoyama S, Laoag-Fernandez JB, Mochizuki S, Yamabe S, Maruo T | title = Vaginoplasty with Interceed absorbable adhesion barrier for complete squamous epithelialization in vaginal agenesis | journal = Am. J. Obstet. Gynecol. | volume = 188 | issue = 5 | pages = 1260–4 |date=May 2003 | pmid = 12748495 | doi = 10.1067/mob.2003.317}}{{cite journal |vauthors=Jackson ND, Rosenblatt PL | title = Use of Interceed Absorbable Adhesion Barrier for vaginoplasty | journal = Obstet Gynecol | volume = 84 | issue = 6 | pages = 1048–50 |date=December 1994 | pmid = 7970464 }} buccal mucosa, amnion, dura mater. or with the support of vaginal stents/expanders.{{cite journal |last1=Barutçu |first1=Ali |last2=Akgüner |first2=Muharrem |title=McIndoe Vaginoplasty with the Inflatable Vaginal Stent |journal=Annals of Plastic Surgery |date=November 1998 |volume=41 |issue=5 |pages=568–9 |doi=10.1097/00000637-199811000-00020|pmid=9827964 }}{{cite journal |last1=Coskun |first1=Ayhan |last2=Coban |first2=Yusuf Kenan |last3=Vardar |first3=Mehmet Ali |last4=Dalay |first4=Ahmet Cemil |title=The use of a silicone-coated acrylic vaginal stent in McIndoe vaginoplasty and review of the literature concerning silicone-based vaginal stents: a case report |journal=BMC Surgery |date=10 July 2007 |volume=7 |issue=1 |page=13 |doi=10.1186/1471-2482-7-13|pmid=17623058 |pmc=1947946 |doi-access=free }} Success of such methods should be determined by sexual function, and not just by vaginal length, as has been done in the past. Ileal or cecal segments may be problematic because of a shorter mesentery, which may produce tension on the neovagina, leading to stenosis. The sigmoid neovagina is thought to be self-lubricating, without the excess mucus production associated with segments of small bowel. Vaginoplasty may create scarring at the introitus (the vaginal opening), which requires additional surgery to correct. Vaginal dilators are required postoperatively to prevent vaginal stenosis from scarring. Inflatable vaginal stents are placed in the vagina deflated and then gently inflated.{{cite journal |last1=Antoniadis |first1=N |last2=Charles |first2=G |last3=Mejías |first3=I |last4=Pabón |first4=R |title=Vaginoplastia: modificación de la técnica de McIndoe usando esponja de gel hemostático|trans-title=Vaginoplasty: modification to McIndoe {{sic|nolink=y|reason=error in source|techique}} using hemostatic gel sponge |journal=Cirugía Plástica Ibero-Latinoamericana |date=March 2011 |volume=37 |issue=1 |pages=73–77 |doi=10.4321/S0376-78922011000100010 |doi-access=free |s2cid=73403359 }} 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.

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 condition can lead active lives and expect a normal lifespan.

It is estimated that CAIS occurs in 1 in 20,400 to 1 in 99,000 individuals with a 46,XY karyotype.{{cite book|author1=Shlomo Melmed|author2=Kenneth S. Polonsky|author3=P. Reed Larsen|author4=Henry M. Kronenberg|title=Williams Textbook of Endocrinology E-Book|url=https://books.google.com/books?id=iPIACwAAQBAJ&pg=PA933|date=11 November 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-34157-8|pages=933–}}{{cite book|author=M. Sperling|title=Pediatric Endocrinology|url=https://books.google.com/books?id=jIxXJCxGNvAC&pg=PA670|date=1 January 2008|publisher=Elsevier Health Sciences|isbn=978-1-4160-4090-3|pages=670–}}

{{Main|Androgen insensitivity syndrome#Other names|l1=Other names for androgen insensitivity syndrome}}

Historically, CAIS has been referred to in the literature under a number of other names, including testicular feminization [syndrome] (deprecated) and Morris syndrome.{{cite journal | vauthors = Mendoza N, Motos MA | title = Androgen insensitivity syndrome | journal = Gynecol. Endocrinol. | volume = 29 | issue = 1 | pages = 1–5 | date = January 2013 | pmid = 22812659 | doi = 10.3109/09513590.2012.705378 | s2cid = 37882159 }}{{cite journal|last1=Mendoza|first1=Nicolas|last2=Rodriguez-Alcalá|first2=Cristina|last3=Motos|first3=Miguel Angel|last4=Salamanca|first4=Alberto|title=Androgen Insensitivity Syndrome: An Update on the Management of Adolescents and Young People|journal=Journal of Pediatric and Adolescent Gynecology|volume=30|issue=1|year=2017|pages=2–8|issn=1083-3188|doi=10.1016/j.jpag.2016.08.013}} PAIS has also been referred to as Reifenstein syndrome, which should not be confused with CAIS.

The first definitive description of CAIS was reported in 1817.{{cite journal | vauthors = Imperato-McGinley J, Canovatchel WJ | title = Complete androgen insensitivity Pathophysiology, diagnosis, and management | journal = Trends Endocrinol. Metab. | volume = 3 | issue = 3 | pages = 75–81 | date = April 1992 | pmid = 18407082 | doi = 10.1016/1043-2760(92)90016-T | s2cid = 35500255 }}{{cite journal|last1=Patterson|first1=Mark N.|last2=McPhaul|first2=Michael J.|last3=Hughes|first3=Ieuan A.|title=8 Androgen insensitivity syndrome|journal=Baillière's Clinical Endocrinology and Metabolism|volume=8|issue=2|year=1994|pages=379–404|issn=0950-351X|doi=10.1016/S0950-351X(05)80258-7|pmid=8092978|url=https://zenodo.org/record/3427335}}{{Dead link|date=December 2023 |bot=InternetArchiveBot |fix-attempted=yes }} The condition became more widely known after it was reviewed and named testicular feminization by American gynecologist John McLean Morris in 1953.

• Georgiann Davis{{cite web | url = http://www.interfaceproject.org/georgiann-davis/ | title = Georgiann Davis | work = The Interface Project | date = November 7, 2012}}
• Seven Graham{{cite news|url=https://www.independent.co.uk/news/uk/home-news/special-report-intersex-women-speak-out-to-protect-the-next-generation-8974892.html|newspaper=The Independent|title=Special report: Intersex women speak out to protect the next generation|first=Sarah|last=Morrison|date=30 November 2013|access-date=19 November 2015}}
• Eden Atwood
• Alicia Roth Weigel

• Complete estrogen insensitivity syndrome

{{Reflist | colwidth = 30em | refs =

{{cite book |vauthors=Achermann JC, Jameson JL | chapter = Disorders of sexual differentiation |veditors=Hauser SL, Kasper DL, Fauci AS, Braunwald E, Longo DL | title = Harrison's endocrinology | publisher = McGraw-Hill Medical Pub. Division | location = New York | year = 2006 | pages = 161–172 | isbn = 978-0-07-145744-6 }}

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{{cite journal |vauthors=Johnston DS, Russell LD, Friel PJ, Griswold MD | title = Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation | journal = Endocrinology | volume = 142 | issue = 6 | pages = 2405–8 |date=June 2001 | pmid = 11356688 | doi = 10.1210/endo.142.6.8317 | doi-access = free | hdl = 1773/4480 | hdl-access = free }}

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{{cite journal |vauthors=Minto CL, Liao KL, Conway GS, Creighton SM | title = Sexual function in women with complete androgen insensitivity syndrome | journal = Fertil. Steril. | volume = 80 | issue = 1 | pages = 157–64 |date=July 2003 | pmid = 12849818 | doi = 10.1016/S0015-0282(03)00501-6 | citeseerx = 10.1.1.543.7011 }}

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{{cite journal | author = Müller J | title = Morphometry and histology of gonads from twelve children and adolescents with the androgen insensitivity (testicular feminization) syndrome | journal = J. Clin. Endocrinol. Metab. | volume = 59 | issue = 4 | pages = 785–9 |date=October 1984 | pmid = 6480805 | doi = 10.1210/jcem-59-4-785 }}

{{cite journal |vauthors=Muñoz-Torres M, Jódar E, Quesada M, Escobar-Jiménez F | title = Bone mass in androgen-insensitivity syndrome: response to hormonal replacement therapy | journal = Calcif. Tissue Int. | volume = 57 | issue = 2 | pages = 94–6 |date=August 1995 | pmid = 7584881 | doi = 10.1007/BF00298426 | s2cid = 30714697 }}

{{cite journal |vauthors = Nichols JL, Bieber EJ, Gell JS |title = Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants |journal = Fertil. Steril. |volume = 91 |issue = 3 |pages = 932.e15–8 |year = 2009 |pmid = 18930210 |doi = 10.1016/j.fertnstert.2008.09.027|doi-access = free }}

{{cite journal |vauthors=Oakes MB, Eyvazzadeh AD, Quint E, Smith YR | title = Complete androgen insensitivity syndrome--a review | journal = J Pediatr Adolesc Gynecol | volume = 21 | issue = 6 | pages = 305–10 |date=December 2008 | pmid = 19064222 | doi = 10.1016/j.jpag.2007.09.006 }}

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{{cite journal |vauthors=Sinnecker GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K | title = Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group | journal = Eur. J. Pediatr. | volume = 156 | issue = 1 | pages = 7–14 |date=January 1997 | pmid = 9007482 | doi = 10.1007/s004310050542 | s2cid = 34427651 }}

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{{cite journal |vauthors=Soule SG, Conway G, Prelevic GM, Prentice M, Ginsburg J, Jacobs HS | title = Osteopenia as a feature of the androgen insensitivity syndrome | journal = Clin. Endocrinol. | volume = 43 | issue = 6 | pages = 671–5 |date=December 1995 | pmid = 8736267 | doi = 10.1111/j.1365-2265.1995.tb00533.x | s2cid = 23119343 }}

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{{cite journal | vauthors = Wisniewski AB, Migeon CJ, ((Meyer-Bahlburg HFL)), Gearhart JP, Berkovitz GD, Brown TR, Money J | year = 2000 | title = Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome | journal = J Clin Endocrinol Metab | volume = 85 | issue = 8| pages = 2664–2669 | doi = 10.1210/jcem.85.8.6742 | pmid = 10946863 | doi-access = free }}

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{{cite journal | vauthors = Zachmann M, ((Prader A)), Sobel EH, Crigler JF, Ritzén EM, Atarés M, Ferrandez A | title = Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls | journal = J. Pediatr. | volume = 108 | issue = 5 Pt 1 | pages = 694–7 |date=May 1986 | pmid = 3701515 | doi = 10.1016/S0022-3476(86)81043-5 }}

{{cite journal |vauthors=Zuccarello D, Ferlin A, Vinanzi C, Prana E, Garolla A, Callewaert L, Claessens F, Brinkmann AO, Foresta C | title = Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility | journal = Clin. Endocrinol. | volume = 68 | issue = 4 | pages = 580–8 |date=April 2008 | pmid = 17970778 | doi = 10.1111/j.1365-2265.2007.03069.x | s2cid = 2783902 }}

}}

{{Medical resources

| DiseasesDB = 29662

| DiseasesDB_mult = {{DiseasesDB2|12975}}

| ICD10 = {{ICD10|E|34|51|e|20}}

| ICD9 = {{ICD9|259.51}}

| ICDO =

| OMIM = 312300

| OMIM_mult = {{OMIM|300068||none}}

| MedlinePlus =

| eMedicineSubj = ped

| eMedicineTopic = 2222

| MeshID = D013734

| GeneReviewsNBK = NBK1429

| GeneReviewsName = Androgen Insensitivity Syndrome

| Orphanet = 99429

}}

;Information

• [https://web.archive.org/web/20110706125708/http://www.rch.org.au/publications/CAIS.pdf An Australian parent/patient booklet on CAIS] (archived)
• [https://www.independent.co.uk/life-style/health-and-families/health-news/the-secret-of-my-sex-411032.html The Secret of My Sex] news article
• [https://abcnews.go.com/Health/MedicalMysteries/Story?id=5465752&page=1 Women With Male DNA All Female] news article at ABCnews.com

{{Gonadal disorder}}

{{X-linked disorders}}

{{Intracellular receptor deficiencies}}

{{DEFAULTSORT:Complete Androgen Insensitivity Syndrome}}

Category:Transcription factor deficiencies

Category:Syndromes

Category:Intersex variations