{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:02:35Z","timestamp":1792141355519,"version":"4.4.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder of sex development (DSD) caused by androgen receptor (AR) gene mutation and present with female phenotypes with male chromosomal karyotype. Primitive bipotent gonads in CAIS differentiate into testes producing androgens and antim\u00fcllerian hormone (AMH). However, androgens cannot stimulate embryonic wolffian ducts into male internal reproductive organs owing to AR defect and hormone resistance, while AMH induces the regression of m\u00fcllerian ducts with the absence of uterus, fallopian tubes, and upper third of the vagina. Thus, with male sex chromosome and testes, individuals with CAIS present with a typical female phenotype, primary amenorrhea (PA) and infertility, spontaneous thelarche during puberty, absent or sparse axillary\/pubic hair, and increased risk of gonadal tumors in cryptorchidism. Though theoretically CAIS can be screened prenatally through a discrepancy between chromosomal karyotype and fetal external genitalia, suspected in bilateral inguinal \u201chernia\u201d cases with female genital phenotype, and considered in cases with elevated testosterone (T) levels but no signs of virilization, the lack of typical symptoms brings great challenges to diagnosis and management. Endocrinological hormone assay is helpful for the identification of CAIS which reveals normal or elevated T levels, elevated luteinizing hormone for impairment of negative feedback of T, and normal follicle-stimulating hormone which is regulated by both sex hormones and inhibin. The diagnosis of CAIS after puberty is similar to the diagnostic workflow of PA with additional tests and should be differentiated with PA-related etiologies and other kinds of DSD, such as Swyer syndrome, Mayer\u2013Rokitanskey\u2013K\u00fcster\u2013Ha\u00fcser syndrome, Leydig cell hypoplasia, and several steroidogenic enzymatic deficiencies. Clinical manifestations, hormonal profiles, chromosomal karyotype, and pelvic imaging can provide comprehensive information for diagnosis. AR gene test or binding capacity can be performed for definitive diagnosis. The management of CAIS includes gonadectomy, hormone supplementation, and psychological support and education. Although with the development of molecular biology and awareness of the clinical entity more cases were reported, diagnostic and management challenges exist due to the disease-related and treatment-related stress including the rarity, untypical clinical manifestations, increased risk of gonadal malignancy, and its influence on physiology and psychology. This review provides a comprehensive overview of the molecular pathogenesis, pathophysiology, diagnostic evaluation, differential diagnosis, and management of CAIS.<\/jats:p>","DOI":"10.3389\/fendo.2025.1600343","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:15:00Z","timestamp":1760415300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular pathogenesis, diagnosis, and management challenges in complete androgen insensitivity syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Chunqing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinjie","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2023.01024","article-title":"Molecular genetics and general management of androgen insensitivity syndrome","volume":"12","author":"Chen","year":"2023","journal-title":"Intractable Rare Dis Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e54550","DOI":"10.7759\/cureus.54550","article-title":"Rare case of complete androgen insensitivity syndrome","volume":"16","author":"Fava Spessoto","year":"2024","journal-title":"Cureus"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1297\/cpe.2022-0058","article-title":"Potential risk of inguinal hernia in complete androgen insensitivity syndrome","volume":"32","author":"Kimizuka","year":"2023","journal-title":"Clin Pediatr Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000031","article-title":"Androgen insensitivity syndrome: a review","volume":"62","author":"Batista","year":"2018","journal-title":"Arch Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2006.11.003","article-title":"Androgen resistance","volume":"20","author":"Hughes","year":"2006","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1590\/s0004-27302005000100012","article-title":"Androgen insensitivity syndrome: clinical, hormonal and molecular analysis of 33 cases","volume":"49","author":"Melo","year":"2005","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2004.09.012","article-title":"The incidence of complete androgen insensitivity in girls with inguinal hernias and assessment of screening by vaginal length measurement","volume":"40","author":"Sarpel","year":"2005","journal-title":"J Pediatr Surg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009213431210","article-title":"A novel explanation for resistance to androgens","volume":"343","author":"Hughes","year":"2000","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2011.08.008","article-title":"Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness","volume":"46","author":"Tasian","year":"2011","journal-title":"J Pediatr Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009213431205","article-title":"Androgen-insensitivity syndrome as a possible coactivator disease","volume":"343","author":"Adachi","year":"2000","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2023.04.130","article-title":"Complete androgen insensitivity Syndrome: A rare case report","volume":"46","author":"Xiao","year":"2023","journal-title":"Asian J Surg"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031264","article-title":"Complete androgen insensitivity syndrome: from bench to bed","volume":"22","author":"Tyutyusheva","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.5114\/aoms\/125584","article-title":"The challenges of androgen insensitivity syndrome","volume":"18","author":"Ovidiu","year":"2021","journal-title":"Arch Med Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00052","article-title":"Epigenetic repression of androgen receptor transcription in mutation-negative androgen insensitivity syndrome (AIS type II)","volume":"103","author":"Hornig","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043453207","article-title":"Alterations of sex differentiation in males: from candidate genes to diagnosis and treatments","volume":"10","author":"Ostrer","year":"2004","journal-title":"Curr Pharm Des"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(53)90359-7","article-title":"The syndrome of testicular feminization in male pseudohermaphrodites","volume":"65","author":"Morris","year":"1953","journal-title":"Am J Obstet Gynecol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195604262541703","article-title":"Testicular feminization in a male pseudohermaphrodite, report of a case","volume":"254","author":"Stern","year":"1956","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2007.09.006","article-title":"Complete androgen insensitivity syndrome\u2013a review","volume":"21","author":"Oakes","year":"2008","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04918-4","article-title":"Single-cell roadmap of human gonadal development","volume":"607","author":"Garcia-Alonso","year":"2022","journal-title":"Nature"},{"key":"B20","volume-title":"Endotext","author":"Feingold","year":"2000"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.diff.2022.07.001","article-title":"Early development of the human embryonic testis","volume":"129","author":"Himelreich Peri\u0107","year":"2023","journal-title":"Differentiation"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/326876a0","article-title":"Separation of the genetic loci for the H-Y antigen and for testis determination on human Y chromosome","volume":"326","author":"Simpson","year":"1987","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1515\/jpem.2005.18.8.739","article-title":"Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature","volume":"18","author":"Ergun-Longmire","year":"2005","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcpc1807497","article-title":"Case 29-2018: A 31-year-old woman with infertility","volume":"379","author":"Coutifaris","year":"2018","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705223362110","article-title":"Serum m\u00fcllerian inhibiting substance assay\u2013a new diagnostic test for disorders of gonadal development","volume":"336","author":"Forest","year":"1997","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/s0303-7207(01)00466-x","article-title":"Molecular basis of androgen insensitivity","volume":"179","author":"Brinkmann","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.semcdb.2015.10.021","article-title":"Ovarian development and disease: The known and the unexpected","volume":"45","author":"Biason-Lauber","year":"2015","journal-title":"Semin Cell Dev Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1056\/NEJM200405203502118","article-title":"Sex determination, differentiation, and identity","volume":"350","author":"Berenbaum","year":"2004","journal-title":"N Engl J Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1226387","article-title":"Diagnostic challenges and management advances in cytochrome P450 oxidoreductase deficiency, a rare form of congenital adrenal hyperplasia, with 46, XX karyotype","volume":"14","author":"Wang","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-016-0482-0","article-title":"Gender identity, gender assignment and reassignment in individuals with disorders of sex development: a major of dilemma","volume":"39","author":"Fisher","year":"2016","journal-title":"J Endocrinol Invest"},{"key":"B31","article-title":"Androgen insensitivity syndrome","volume-title":"StatPearls","author":"Singh","year":"2023"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60071-3","article-title":"Androgen insensitivity syndrome","volume":"380","author":"Hughes","year":"2012","journal-title":"Lancet"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e4334","DOI":"10.1002\/pro.4334","article-title":"Topological dynamics of an intrinsically disordered N-terminal domain of the human androgen receptor","volume":"31","author":"Sheikhhassani","year":"2022","journal-title":"Protein Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.002r001","article-title":"Structural organization of the human androgen receptor gene","volume":"2","author":"Kuiper","year":"1989","journal-title":"J Mol Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1210\/edrv-16-3-271","article-title":"Androgen receptor defects: historical, clinical, and molecular perspectives","volume":"16","author":"Quigley","year":"1995","journal-title":"Endocr Rev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(95)03608-a","article-title":"Defects of androgen receptor function: from sex reversal to motor neurone disease","volume":"112","author":"MacLean","year":"1995","journal-title":"Mol Cell Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1615\/critreveukargeneexpr","article-title":"Androgen receptor: an overview","volume":"5","author":"Chang","year":"1995","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.12.008","article-title":"Clinical characteristics and molecular genetics of complete androgen insensitivity syndrome patients: a series study of 30 cases from a Chinese tertiary medical center","volume":"115","author":"Zhang","year":"2021","journal-title":"Fertil Steril"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1177\/23247096231157918","article-title":"An early case of complete androgen insensitivity syndrome","volume":"11","author":"Matalka","year":"2023","journal-title":"J Investig Med High Impact Case Rep"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e14292","DOI":"10.1111\/and.14292","article-title":"Novel androgen receptor gene variant containing a frameshift mutation in a patient with complete androgen insensitivity syndrome","volume":"54","author":"Chen","year":"2022","journal-title":"Andrologia"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-022-01894-4","article-title":"Clinical characteristics, AR gene variants, and functional domains in 64 patients with androgen insensitivity syndrome","volume":"46","author":"Liu","year":"2023","journal-title":"J Endocrinol Invest"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13040929","article-title":"Androgen insensitivity syndrome with bilateral gonadal sertoli cell lesions, sertoli-leydig cell tumor, and paratesticular leiomyoma: A case report and first systematic literature review","volume":"13","author":"Karseladze","year":"2024","journal-title":"J Clin Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4103\/ijem.IJEM_345_16","article-title":"Mutational analysis of androgen receptor gene in two families with androgen insensitivity","volume":"21","author":"Akella","year":"2017","journal-title":"Indian J Endocrinol Metab"},{"key":"B44","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1267\/ahc.19013","article-title":"Hypothalamic kisspeptin expression in hyperandrogenic female rats and aging rats","volume":"52","author":"Iwata","year":"2019","journal-title":"Acta Histochem Cytochem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0363-7","article-title":"Metabolic regulation of kisspeptin - the link between energy balance and reproduction","volume":"16","author":"Navarro","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/978-1-4614-6199-9_14","article-title":"Kisspeptin and GnRH pulse generation","volume":"784","author":"Okamura","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02127-y","article-title":"Androgen insensitivity syndrome: a review","volume":"46","author":"Delli Paoli","year":"2023","journal-title":"J Endocrinol Invest"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.11604\/pamj.2016.25.199.10758","article-title":"Complete androgen insensitivity syndrome or testicular feminization: review of literature based on a case report","volume":"25","author":"Souhail","year":"2016","journal-title":"Pan Afr Med J"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000001521","article-title":"Complete androgen insensitivity syndrome diagnosed after inguinal surgery in era of modern technology: a case report","volume":"86","author":"Shrestha","year":"2023","journal-title":"Ann Med Surg (Lond)"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1159\/000477599","article-title":"Bone mineral density in women living with complete androgen insensitivity syndrome and intact testes or removed gonads","volume":"11","author":"Bertelloni","year":"2017","journal-title":"Sex Dev"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2012.06.013","article-title":"Complete androgen insensitivity syndrome associated with bilateral Sertoli cell adenomas and paratesticular leiomyomas: case report and review of the literature","volume":"9","author":"Siminas","year":"2013","journal-title":"J Pediatr Urol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.15231","article-title":"Early diagnosis of androgen insensitivity syndrome with cell-free fetal DNA screening: A case report","volume":"164","author":"Miller","year":"2024","journal-title":"Int J Gynaecol Obstet"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1177\/10668969221085292","article-title":"Yolk sac tumor in an infant with androgen insensitivity syndrome: A case report and review of the literature","volume":"30","author":"Yang","year":"2022","journal-title":"Int J Surg Pathol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1159\/000493645","article-title":"Management of gonads in adults with androgen insensitivity: an international survey","volume":"90","author":"Tack","year":"2018","journal-title":"Horm Res Paediatr"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s10029-024-02982-5","article-title":"A case of complete androgen insensitivity syndrome combined with bilateral inguinal hernia","volume":"28","author":"Zheng","year":"2024","journal-title":"Hernia"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/08941939.2019.1602690","article-title":"Genetic analysis reveals complete androgen insensitivity syndrome in female children surgically treated for inguinal hernia","volume":"34","author":"Listyasari","year":"2021","journal-title":"J Invest Surg"},{"key":"B57","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1055\/s-0042-1753551","article-title":"Primary amenorrhea and differences of sex development","volume":"40","author":"Naroji","year":"2022","journal-title":"Semin Reprod Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.108","article-title":"Management of disorders of sex development","volume":"10","author":"Hiort","year":"2014","journal-title":"Nat Rev Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1361032","article-title":"Anti-M\u00fcllerian hormone, testicular descent and cryptorchidism","volume":"15","author":"Rey","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8313162","article-title":"Psychological aspects of androgen insensitivity syndrome: two cases illustrating therapeutical challenges","volume":"2017","author":"Pritsini","year":"2017","journal-title":"Case Rep Endocrinol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4103\/jhrs.JHRS_107_16","article-title":"Chromosomal aberrations in primary amenorrhea: A retrospective study","volume":"12","author":"Korgaonkar","year":"2019","journal-title":"J Hum Reprod Sci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16071268","article-title":"Different clinical presentations and management in complete androgen insensitivity syndrome (CAIS)","volume":"16","author":"Lanciotti","year":"2019","journal-title":"Int J Environ Res Public Health"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2019.06.005","article-title":"A management protocol for gonad preservation in patients with androgen insensitivity syndrome","volume":"32","author":"Weidler","year":"2019","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.13121068","article-title":"Evaluation of retained testes in adolescent girls and women with complete androgen insensitivity syndrome","volume":"268","author":"Nakhal","year":"2013","journal-title":"Radiology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-017-9084-9","article-title":"AR mutations in 28 patients with androgen insensitivity syndrome (Prader grade 0-3)","volume":"60","author":"Wang","year":"2017","journal-title":"Sci China Life Sci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22046","article-title":"The androgen receptor gene mutations database: 2012 update","volume":"33","author":"Gottlieb","year":"2012","journal-title":"Hum Mutat"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021658","article-title":"Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene","volume":"88","author":"Melo","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/path.1890","article-title":"Testicular development in the complete androgen insensitivity syndrome","volume":"208","author":"Hannema","year":"2006","journal-title":"J Pathol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s13256-021-02738-0","article-title":"Complete androgen insensitivity syndrome in a 13-year-old Lebanese child, reared as female, with bilateral inguinal hernia: a case report","volume":"15","author":"Farah","year":"2021","journal-title":"J Med Case Rep"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2017.02.013","article-title":"Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis","volume":"13","author":"Chaudhry","year":"2017","journal-title":"J Pediatr Urol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13030785","article-title":"A risk of gonadoblastoma in familial Swyer syndrome-A case report and literature review","volume":"13","author":"Rudnicka","year":"2024","journal-title":"J Clin Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0863","article-title":"Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis","volume":"89","author":"Canto","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e2280","DOI":"10.1002\/mgg3.2280","article-title":"Recurrent human 16p11.2 microdeletions in type I Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome patients in Chinese Han population","volume":"12","author":"Su","year":"2024","journal-title":"Mol Genet Genomic Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-022-0969-3","article-title":"Update on Mayer-Rokitansky-K\u00fcster-Hauser syndrome","volume":"16","author":"Chen","year":"2022","journal-title":"Front Med"},{"key":"B75","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s13023-020-01491-9","article-title":"Mayer-Rokitansky-K\u00fcster-Hauser (MRKH) syndrome: a comprehensive update","volume":"15","author":"Herlin","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/omcr\/omab015","article-title":"Leydig cell hypoplasia type 1 diagnosed in early childhood with inactivating mutation in LHCGR gene","volume":"2021","author":"\u00c7\u00f6mlek","year":"2021","journal-title":"Oxf Med Case Rep"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197610282951801","article-title":"Leydig-cell agenesis: a cause of male pseudohermaphroditism","volume":"295","author":"Berthez\u00e8ne","year":"1976","journal-title":"N Engl J Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.4158\/ACCR-2019-0152","article-title":"LeydIG cell hypoplasia: a unique paradox in the diagnosis of 46, XY disorders of sex development","volume":"6","author":"Jahan","year":"2020","journal-title":"AACE Clin Case Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1046\/j.0300-0664.2001.01437.x","article-title":"Leydig cell hypoplasia: cases with new mutations, new polymorphisms and cases without mutations in the luteinizing hormone receptor gene","volume":"56","author":"Richter-Unruh","year":"2002","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B80","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1210\/jc.2011-2161","article-title":"The syndrome of 17,20 lyase deficiency","volume":"97","author":"Miller","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B81","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1530\/EDM-22-0338","article-title":"Diagnosis of 17-alpha hydroxylase deficiency performed late in life in a patient with a 46,XY karyotype","volume":"2023","author":"Bou\u00e7a","year":"2023","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B82","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13048-017-0312-9","article-title":"Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review","volume":"10","author":"Bai","year":"2017","journal-title":"J Ovarian Res"},{"key":"B83","article-title":"Ambiguous genitalia in the newborn","volume-title":"Endotext","author":"Fl\u00fcck","year":"2023"},{"key":"B84","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/0002-9378(76)90160-5","article-title":"The age of occurrence of gonadal tumors in intersex patients with a Y chromosome","volume":"124","author":"Manuel","year":"1976","journal-title":"Am J Obstet Gynecol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13255","article-title":"Gonadal tumour risk in 292 phenotypic female patients with disorders of sex development containing Y chromosome or Y-derived sequence","volume":"86","author":"Huang","year":"2017","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2014.09.015","article-title":"Risk of Malignancy and need for surgery in pediatric patients with Morris or Y-chromosome Turner syndrome: A multicenter survey","volume":"28","author":"Esposito","year":"2015","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.03.110","article-title":"Complete androgen insensitivity: the role of the surgeon","volume":"180","author":"Purves","year":"2008","journal-title":"J Urol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30197-9","article-title":"Oestrogen versus androgen in hormone-replacement therapy for complete androgen insensitivity syndrome: a multicentre, randomised, double-dummy, double-blind crossover trial","volume":"6","author":"Birnbaum","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1530\/EDM-23-0063","article-title":"Induction of lactation in a patient with complete androgen insensitivity syndrome","volume":"2023","author":"Voon","year":"2023","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1177\/0890334419888752","article-title":"Induced lactation in a mother through surrogacy with complete androgen insensitivity syndrome (CAIS)","volume":"36","author":"LeCain","year":"2020","journal-title":"J Hum Lact"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.18502\/ijrm.v21i12.15036","article-title":"Sex assignment and psychosexual peculiarities of individuals with different forms of androgen insensitivity syndrome: A qualitative study","volume":"21","author":"Kristesashvili","year":"2024","journal-title":"Int J Reprod BioMed"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1159\/000527433","article-title":"Challenges waiting for an adult with DSD","volume":"96","author":"Nowotny","year":"2023","journal-title":"Horm Res Paediatr"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2017.08.009","article-title":"Increased psychiatric morbidity in women with complete androgen insensitivity syndrome or complete gonadal dysgenesis","volume":"101","author":"Engberg","year":"2017","journal-title":"J Psychosom Res"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/342420","article-title":"The investigation of quality of life in 87 Chinese patients with disorders of sex development","volume":"2015","author":"Wang","year":"2015","journal-title":"BioMed Res Int"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1600343\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T04:15:02Z","timestamp":1760415302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1600343\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":94,"alternative-id":["10.3389\/fendo.2025.1600343"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1600343","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"article-number":"1600343"}}