Sex assignment and psychosexual peculiarities of individuals with different forms of androgen insensitivity syndrome: A qualitative study


Background: A mismatch between chromosomal, gonadal, and phenotypic sexes in individuals with androgen insensitivity syndrome (AIS) creates problems in sex assignment and psychosexual identification.

Objective: To identify psychosexual and sex assignment peculiarities of individuals with different forms of AIS.

Materials and Methods: In this qualitative study, 41 individuals with AIS aged between 15 and 31 yr who referred to the Universe Center for Reproductive Medicine Tbilisi, Georgia between 2016 and 2021 were studied. All individuals underwent clinical, genealogical, hormonal, ultrasonographic, and cytogenetic examinations. In-depth interviews and medical records assessed psychosexual profiles and sex assignment histories.

Results: 32 cases were diagnosed with the complete form of AIS (CAIS), 8 individuals with the partial form (PAIS), and one with a mild form (MAIS). Individuals with CAIS and PAIS were assessed at birth and raised as girls. Individuals with CAIS and female psychosexual disposition were referred to us due to amenorrhea. Adolescent individuals with PAIS assessed as girls referred to us due to masculinization detected in puberty. An individual with MAIS was assessed at birth and raised as a boy with male genitalia. All individuals with AIS had typical hormonal data and sex chromosome complex for men. 20 sexually active individuals with CAIS had penile-vaginal contact with the man. None of the individuals with CAIS and PAIS thought about gender reassignment after being diagnosed, only the individual with MAIS aimed for male-to-female transition.

Conclusion: Psychosexual identification remains a significant challenge in AIS management. Detection of female psychosexual disposition in one participant that is unusual to MAIS may be associated with somatic mosaicism of the androgen receptor gene.

Key words: Androgen insensitivity syndrome, Androgen receptor, Sex development disorders, Ambiguous genitalia.

[1] Batista RL, Frade Costa EM, de Santi Rodrigues A, Lisboa Gomes N, Faria Jr JA, Nishi MY, et al. Androgen insensitivity syndrome: A review. Arch Endocrinol Metab 2018; 62: 227–235.

[2] Ovidiu B, Marcu DR, Dan LD, Mischianu DL, Catalina Poiana C, Camelia C, et al. The challenges of androgen insensitivity syndrome. Arch Med Sci 2022; 18: 881–889.

[3] Jiang X, Teng Y, Chen X, Liang N, Li Z, Liang D, et al. Six novel mutation analysis of the androgen receptor gene in 17 Chinese individuals with androgen insensitivity syndrome. Clin Chim Acta 2020; 506: 180–186.

[4] Liu Q, Yin X, Li P. Clinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese individuals. Reprod Biol Endocrinol 2020; 18: 34.

[5] Gottlieb B, Beitel LK, Nadarajah A, Paliouras M, Trifiro M. The androgen receptor gene mutations database: 2012 update. Hum Mutat 2012; 33: 887–894.

[6] Gulia C, Baldassarra S, Zangari A, Briganti V, Gigli S, Gaffi M, et al. Androgen insensitivity syndrome. Eur Rev Med Pharmacol Sci 2018; 22: 3873–3887.

[7] Eisermann K, Wang D, Jing Y, Pascal LE, Wang Z. Androgen receptor gene mutation, rearrangement, polymorphism. Transl Androl Urol 2013; 2: 137–147.

[8] Batista RL, de Santi Rodrigues A, Machado AZ, Nishi MY, Cunha FS, Silva RB, et al. Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor. J Pediatr Endocrinol Metab 2018; 31: 223–228.

[9] Fisher AD, Ristori J, Fanni E, Castellini G, Forti G, Maggi M. Gender identity, gender assignment and reassignment in individuals with disorders of sex development: A major of dilemma. J Endocrinol Invest 2016; 39: 1207–1224.

[10] Lek N, Tadokoro-Cuccaro R, Whitchurch JB, Mazumder B, Miles H, Prentice P, et al. Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices. EBioMedicine 2018; 36: 401–409.

[11] de la Vega JAB, Fernández-Cancio M, Bernal S, Audí L. Complete androgen insensitivity syndrome associated with male gender identity or female precocious puberty in the same family. Sex Dev 2015; 9: 75–79.

[12] Markosyan R, Ahmed SF. Sex assignment in conditions affecting sex development. J Clin Res Pediatr Endocrinol 2017; 9: 106–112.

[13] Tordjman KM, Yaron M, Berkovitz A, Botchan A, Sultan C, Lumbroso S. Fertility after high-dose testosterone and intracytoplasmic sperm injection in a patient with androgen insensitivity syndrome with a previously unreported androgen receptor mutation. Andrologia 2013; 46: 793–806.

[14] Mendonca BB. Gender assignment in individuals with disorder of sex development. Curr Opin Endocrinol Diabetes Obes 2014; 21: 511–514.

[15] Cools M, Looijenga LH, Wolffenbuttel KP, T'Sjoen G. Managing the risk of germ cell tumourigenesis in disorders of sex development individuals. Endocr Dev 2014; 27: 185–196.

[16] Van Hemmen J, Veltman DJ, Hoekzema E, Cohen- Kettenis PT, Dessens AB, Bakker J. Neural activation during mental rotation in complete androgen insensitivity syndrome: The influence of sex hormones and sex chromosomes. Cereb Cortex 2016; 26: 1036–1045.