Archives of Sexual Behavior

, Volume 40, Issue 3, pp 635–638 | Cite as

Male Gender Identity in Complete Androgen Insensitivity Syndrome

  • Guy T’SjoenEmail author
  • Griet De Cuypere
  • Stan Monstrey
  • Piet Hoebeke
  • F. Kenneth Freedman
  • Mahesh Appari
  • Paul-Martin Holterhus
  • John Van Borsel
  • Martine Cools
Clinical Case Report Series


Women and girls with complete androgen insensitivity syndrome (CAIS) invariably have a female typical core gender identity. In this case report, we describe the first case of male gender identity in a CAIS individual raised female leading to complete sex reassignment involving both androgen treatment and phalloplasty. CAIS was diagnosed at age 17, based on an unambiguously female phenotype, a 46,XY karyotype, and a 2660delT androgen receptor (AR) gene mutation, leading to a premature stop in codon 807. Bilateral gonadectomy was performed but a short period of estrogen treatment induced a negative emotional reaction and treatment was stopped. Since the age of 3, childhood-onset cross gender behavior had been noticed. After a period of psychotherapy, persisting male gender identity was confirmed. There was no psychiatric co-morbidity and there was an excellent real life experience. Testosterone substitution was started, however without inducing any of the desired secondary male characteristics. A subcutaneous mastectomy was performed and the patient received phalloplasty by left forearm free flap and scrotoplasty. Testosterone treatment was continued, without inducing virilization, and bone density remained normal. The patient qualifies as female-to-male transsexual and was treated according to the Standards of Care by the World Professional Association for Transgender Health with good outcome. However, we do not believe that female sex of rearing as a standard procedure should be questioned in CAIS. Our case challenges the role of a functional AR pathway in the development of male gender identity.


Complete androgen insensitivity syndrome Gender identity disorder Transsexualism Disorder of sex development 



Martine Cools is supported by the Flanders Research Foundation (FWO).


  1. Appari, M., Werner, R., Wünsch, L., Cario, G., Demeter, J., Hiort, O., et al. (2009). Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome. Journal of Molecular Medicine, 87, 623–632.PubMedCrossRefGoogle Scholar
  2. Avila, D. M., Wilson, C. M., Nandi, N., Griffin, J. E., & McPhaul, M. J. (2002). Immunoreactive AR and genetic alterations in subjects with androgen resistance and undetectable AR levels in genital skin fibroblast ligand-binding assays. Journal of Clinical Endocrinology and Metabolism, 87, 182–188.PubMedCrossRefGoogle Scholar
  3. Baldazzi, L., Baroncini, C., Pirazzoli, P., Balsamo, A., Capelli, M., Marchetti, G., et al. (1994). Two mutations causing complete androgen insensitivity: A frame-shift in the steroid binding domain and a Cys → Phe substitution in the second zinc finger of the androgen receptor. Human Molecular Genetics, 3, 1169–1170.PubMedCrossRefGoogle Scholar
  4. Cheikhelard, A., Morel, Y., Thibaud, E., Lortat-Jacob, S., Jaubert, F., Polak, M., et al. (2008). Long-term follow-up and comparison between genotype and phenotype in 29 cases of complete androgen insensitivity syndrome. Journal of Urology, 180, 1496–1501.PubMedCrossRefGoogle Scholar
  5. Chung, H. W., Kim, S. C., & Kim, H. L. (1998). Frame-shift mutation in hormone binding domain of human androgen receptor gene causes complete androgen insensitivity. Molecules and Cells, 8, 741–745.PubMedGoogle Scholar
  6. Foradori, C. D., Weiser, M. J., & Handa, R. J. (2008). Non-genomic actions of androgens. Frontiers in Neuroendocrinology, 29, 169–181.PubMedCrossRefGoogle Scholar
  7. Hannema, S. E., Scott, I. S., Hodapp, J., Martin, H., Coleman, N., Schwabe, J. W., et al. (2004). Residual activity of mutant androgen receptors explains Wolffian duct development in the complete androgen insensitivity syndrome. Journal of Endocrinology and Metabolism, 89, 5815–5822.CrossRefGoogle Scholar
  8. Hines, M., Ahmed, S. F., & Hughes, I. A. (2003). Psychological outcomes and gender-related development in complete androgen insensitivity syndrome. Archives of Sexual Behavior, 32, 93–101.PubMedCrossRefGoogle Scholar
  9. Hiort, O., Sinnecker, G. H., Holterhus, P. M., Nitsche, E. M., & Kruse, K. (1998). Inherited and de novo androgen receptor gene mutations: Investigation of single-case families. Journal of Pediatrics, 132, 939–943.PubMedCrossRefGoogle Scholar
  10. Holterhus, P. M., Brüggenwirth, H. T., Hiort, O., Kleinkauf-Houcken, A., Kruse, K., Sinnecker, G. H., et al. (1997). Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome. Journal of Clinical Endocrinology and Metabolism, 82, 3584–3589.PubMedCrossRefGoogle Scholar
  11. Holterhus, P. M., Wiebel, J., Sinnecker, G. H., Brüggenwirt, H. T., Sippell, W. G., Brinkmann, A. O., et al. (1999). Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome. Pediatric Research, 46, 684–690.PubMedCrossRefGoogle Scholar
  12. Jürgensen, M., Hiort, O., Holterhus, P.-M., & Thyen, U. (2007). Gender role behavior in children with XY karyotype and disorders of sex development. Hormones and Behavior, 51, 443–453.PubMedCrossRefGoogle Scholar
  13. Kulshreshtha, B., Philibert, P., Eunice, M., Khandelwal, S. K., Mehta, M., Audran, F., et al. (2009). Apparent male gender identity in a patient with complete androgen insensitivity syndrome [Letter to the Editor]. Archives of Sexual Behavior, 38, 873–875.PubMedCrossRefGoogle Scholar
  14. Mazur, T. (2005). Gender dysphoria and gender change in androgen insensitivity or micropenis. Archives of Sexual Behavior, 34, 411–421.PubMedCrossRefGoogle Scholar
  15. Meyer, W., Bockting, W. O., Cohen-Kettenis, P., Coleman, E., DiCeglie, D., Devor, H., et al. (2001). The standards of care for gender identity disorders—Sixth version. Journal of Psychology and Human Sexuality, 13, 1–30.CrossRefGoogle Scholar
  16. Meyer-Bahlburg, H. F. L. (2009). Concerns regarding gender change to male in a 46,XY child with complete androgen insensitivity syndrome: Comment on Kulshreshtha et al. (2009) [Letter to the Editor]. Archives of Sexual Behavior, 38, 876–877.PubMedCrossRefGoogle Scholar
  17. Money, J. (1991). Biographies of gender and hermaphroditism in paired comparisons. Amsterdam: Elsevier.Google Scholar
  18. Monstrey, S., Hoebeke, P., Selvaggi, G., Ceulemans, P., Van Landuyt, K., Blondeel, P., et al. (2009). Penile reconstruction: Is the radial forearm flap really the standard technique? Plastic and Reconstructive Surgery, 124, 510–518.PubMedCrossRefGoogle Scholar
  19. Mordaunt, M. (2006). Pitch and intonation. In R. K. Adler, S. Hirsch, & M. Mordaunt (Eds.), Voice and communication therapy for the transgender/transsexual client: A comprehensive clinical guide (pp. 169–207). San Diego, CA: Plural Publishing.Google Scholar
  20. Rodien, P., Mebarki, F., Mowszowicz, I., Chaussain, J. L., Young, J., Morel, Y., et al. (1996). Different phenotypes in a family with androgen insensitivity caused by the same M780I point mutation in the androgen receptor gene. Journal of Clinical Endocrinology and Metabolism, 81, 2994–2998.PubMedCrossRefGoogle Scholar
  21. Sato, T., Matsumoto, T., Kawano, H., Watanabe, T., Uematsu, Y., Sekine, K., et al. (2004). Brain masculinization requires androgen receptor function. Proceedings of the National Academy of Sciences of the United States of America, 101, 1673–1678.PubMedCrossRefGoogle Scholar
  22. Soriano Guillen, L., Muñoz Calvo, M. T., Martinez Pérez, J., Pozo-Roman, J., Marin-Sobrino, M. A., Gonzalez Medeiro, I., et al. (2002). Deletion of thymine at position 2298 in exon 5 of the androgenic receptor gene causing complete androgen insensitivity syndrome. Anales españoles de pediatria, 56, 347–352.PubMedGoogle Scholar
  23. Wisniewski, A. B., Migeon, C. J., Meyer-Bahlburg, H. F. L., Gearhart, J. P., Berkovitz, G. D., Brown, T. R., et al. (2000). Complete androgen insensitivity syndrome: Long-term medical, surgical, and psychosexual outcome. Journal of Clinical Endocrinology and Metabolism, 85, 2664–2669.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Guy T’Sjoen
    • 1
    Email author
  • Griet De Cuypere
    • 1
  • Stan Monstrey
    • 2
  • Piet Hoebeke
    • 3
  • F. Kenneth Freedman
    • 4
  • Mahesh Appari
    • 5
  • Paul-Martin Holterhus
    • 5
  • John Van Borsel
    • 6
  • Martine Cools
    • 7
  1. 1.Department of Endocrinology and Center for Sexology and GenderproblemsGhent University HospitalGhentBelgium
  2. 2.Department of Plastic SurgeryGhent University HospitalGhentBelgium
  3. 3.Department of UrologyGhent University HospitalGhentBelgium
  4. 4.AnchorageUSA
  5. 5.Division of Pediatric Endocrinology and Diabetes, Department of PediatricsUniversity Hospital Schleswig–Holstein Campus Kiel, Christian Albrechts University of KielKielGermany
  6. 6.Department of OtorhinolaryngologyGhent University HospitalGhentBelgium
  7. 7.Department of Pediatric EndocrinologyGhent University HospitalGhentBelgium

Personalised recommendations