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Review
. 2021 Jan 27;22(3):1264.
doi: 10.3390/ijms22031264.

Complete Androgen Insensitivity Syndrome: From Bench to Bed

Nina Tyutyusheva  1 , Ilaria Mancini  2 , Giampiero Igli Baroncelli  1 , Sofia D'Elios  1 , Diego Peroni  1 , Maria Cristina Meriggiola  2 , Silvano Bertelloni  1
Affiliations
Review

Complete Androgen Insensitivity Syndrome: From Bench to Bed

Nina Tyutyusheva et al. Int J Mol Sci. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The proband (indicated by the arrow) is a young 46,XY woman (25 years old) with CAIS, in whom the AR variant p.Trp797* was found. Subsequently, the same mutation was detected in the 46,XY sister with CAIS (⬤) and in other affected 46,XY family members with the same DSD (⬤). Female 46,XX carriers were suspected but not proven by molecular analysis of AR.
Figure 2
Figure 2
Bone mineral density (BMD) assessed by DXA at (a) lumbar spine (L), (b) femoral neck (FN) and (c) total body (TB) in a sample of 18 women with CAIS (⬤) during HRT (17-β-estradiol 2 mg/daily) (T0 = baseline data, T1 = 1–3 years, T2 = 4–6 years). Control group (◆) consisted of 32 healthy age-matched 46,XX women (drawn from 45).
See this image and copyright information in PMC

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