Complete Androgen Insensitivity Syndrome: From Bench to Bed

Int J Mol Sci. 2021 Jan 27;22(3):1264. doi: 10.3390/ijms22031264.

Abstract

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.

Keywords: AR gene; androgen receptor; bone health; complete androgen insensitivity syndrome; gonadal neoplasia; gonadal removal; hormonal substitutive therapy.

Publication types

  • Review

MeSH terms

  • Androgen-Insensitivity Syndrome / drug therapy*
  • Androgen-Insensitivity Syndrome / genetics
  • Androgen-Insensitivity Syndrome / pathology
  • Androgens / therapeutic use
  • Chromosomes, Human, X / drug effects
  • Chromosomes, Human, X / genetics*
  • Female
  • Gonads / drug effects
  • Hormone Replacement Therapy*
  • Humans
  • Karyotype
  • Male
  • Mutation / genetics
  • Receptors, Androgen / genetics*

Substances

  • Androgens
  • Receptors, Androgen