Androgen Insensitivity Syndrome (AIS)

Androgen receptor 3-d model[1]


The following symptomatology are found in complete and partial androgen insensitivity syndrome:

  • Presence of bilateral inguinal mass during birth. These masses will be identified as the undescended testes after surgery.
  • Primary amenorrhea among the adolescents. Some children may be reared as females with male internal gonads.
  • Gynecomastia in males due to low testosterone secretions and high serum estradiol. 
  • Impaired phallic (penile) development due to high estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to the testosterone [5]. 
  • Absence of axillary and pubic hair during puberty due to low virilizing hormone
  • Reduced mean clitoral length [6]
  • Variable genital appearance


The following laboratories and test are routinely used in patients suspected of having androgen insensitivity syndrome:

  • Genetic karyotyping with the use of fluorescent in situ Hybridization (FISH) probe in identifying the Y sex chromosome.
  • Serum levels of testosterone and dihydrotestosterone to establish normal steroidogensis [7].
  • Mutation analysis of the androgen receptor gene commercially available assays to clinch the diagnosis of AIS.
  • Pelvic ultrasound and computed tomography (CT scan) to identify the ovaries and testes in the pelvic area and other aberrant structures (testicular carcinoma).
  • Diagnostic laparotomy to visualize the internal gonads which may conclude with a bilateral orchiectomy to prevent malignant degenerations.


The medical care of a patient suffering from androgen insensitive syndrome is conveniently divided into hormone replacement therapy (HRT) and psychological support [8]. The common HRT agents used in AIS are testosterone and dihydrotestosterone (DHT), where DHT is noted to be more stable because it could not be aromatized to estrogen hormone in the serum.

Psychological support is the most important form of medical therapy for AIS to assist patients in coping with the social stigmata and psychological stresses brought about by the disorder [9]. A pediatric psychologist is often times sought for to help the child overcome the age appropriate manner and cognitive functions.

The standard surgical care for patients with AIS is orchiectomy to prevent the malignant degeneration of the testes intraabdominally [10]. By convention, orchiectomy is usually performed early in childhood to abate any psychological issues linked to gender identity and confusion with the child. Although the exact age where orchiectomy should be performed remains debatable at this point.


The general prognosis for complete AIS is practically good especially if the testicular tissue is removed in the right time and exogenous testosterone is adequately supplied. Patients with CAIS can live a normal life without any observable decrease in life expectancy. In partial AIS, prognosis depends on the appearance of the external and internal genitals.


The following clinical disorders are known complications of Androgen insensitivity syndrome:


Androgen insensitive syndrome is a genetic disease dispersed in the family tree in an X-linked recessive pattern of gene transmission. The mutated chromosome has been found in loci of the X sex chromosome in all cases of AIS. Because males have only one X chromosome, they are more prone to express the AIS traits compared to the female counterpart that has two X sex chromosomes. Although three fourths of the AIS carriers are females that is why genetic counselling with carrier mothers is a prudent preventive practice in its management.


There are no exact clinical data on the incidence AIS internationally. A Danish cohort study on hospitalized cases of AIS reveals an incidence rate of 1 case per 20,040 male live births. The complete form of AIS or CAIS appears to be more frequent than the partial AIS (PAIS) forms worldwide. An international study of sex development disorder registered an 11% incidence of AIS with genital anomalies and 5.2% has a confirmed androgen receptor mutation problem [3].

Sex distribution
Age distribution


The basic pathogenesis in the development of AIS is on the mutation of the androgen receptor gene that results in a non-functional receptor for the androgen hormones. This androgen receptor gene has been localized in the X chromosome in the short arms of q11 to 13.

A complete gene deletion will eventually result in a complete AIS and an incomplete deletion will result in a partial AIS defect. Late onset AIS may occur in Kennedy disease where a bulbar atrophy results in androgen insensitivity presenting as postpubertal gynecomastia [4].


Androgen insensitive dyndrome among the neonates is not preventable; thus, there are no modifiable precautions that may be resorted to avert its expression. Given the dire complications like testicular cancers, the early diagnosis and removal of the testes from the abdomen is an imperative move in the prevention of AIS complications.

Genetic counselling for parents and carriers may reduce its incidence among offspring given that there is a 25% chance of AIS penetrance in the succeeding siblings from the same mother.


Androgen insensitivity syndrome (AIS) is a clinical disease characterized by genotypic male person (with XY sex chromosomes) which becomes insensitive to androgens (male testosterone) and shows phenotypic traits of a female. AIS is formerly referred to as testicular feminization which is identified as an X-linked recessive condition that hampers normal physical masculinization among male patients.

The insensitivity of the subject to the virilizing hormone could either be complete or partial depending on the number of residual receptor function (androgen receptors). Patients suffering from complete androgen insensitivity syndrome (CAIS) will have a complete female external genitalia [1]. Majority of these male patients will become infertile and develop gynecomastia, although, in rare cases of AIS loaded with substantial amounts of exogenous testosterone can becomes fertile again [2]. Although complete cases of AIS may present with female external genitalia, the internal gonads like the testes are present in both complete and partial cases producing physiologically active amounts of testosterone in the serum.

Patient Information


Androgen insensitivity syndrome (AIS) is a clinical disease characterized by genotypic male showing feminine physical traits due to androgen insensitivity.


The cause of androgen insensitivity syndrome is a mutation in the androgen receptor gene which is localized on the X chromosome.


Undescended testes, gynecomastia, absence of axillary and pubic hairs, and variable genital appearances are the symptoms of AIS.


Genetic karyotyping, testosterone assays, ultrasound imaging, and diagnostic laparotomy are done to diagnose AIS.

Treatment and follow-up

Hormonal replacement therapy, psychological support, and surgical orchiectomy are usually necessary to treat AIS and its possible complications.


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  • Oakes MB, Eyvazzadeh AD, Quint E, Smith YR. Complete androgen insensitivity syndrome--a review. J Pediatr Adolesc Gynecol. Dec 2008; 21(6):305-10.
  • 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. Jun 30 2013.
  • Cox K, Bryce J, Jiang J, et al. Novel Associations in Disorders of Sex Development: Findings from the I-DSD Registry. J Clin Endocrinol Metab. Feb 2014; 99(2):E348-55.
  • Dejager S, Bry-Gauillard H, Bruckert E, Eymard B, Salachas F, LeGuern E, et al. A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length. J Clin Endocrinol Metab. August 2002; 87:3893-3901.
  • Hellmann P, Christiansen P, Johannsen TH, Main KM, Duno M, Juul A. Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia. Arch Dis Child. May 2012; 97(5):403-9.
  • Crouch NS, Michala L, Creighton SM, Conway GS. Androgen-dependent measurements of female genitalia in women with complete androgen insensitivity syndrome. BJOG. Jan 2011; 118(1):84-7.
  • Pieper CC, Teismann IK, Konrad C, Heindel WL, Schiffbauer H. Changes of pituitary gland volume in Kennedy disease. AJNR Am J Neuroradiol. Dec 2013; 34(12):2294-7.
  • Bertelloni S, Dati E, Baroncelli GI, Hiort O. Hormonal management of complete androgen insensitivity syndrome from adolescence onward. Horm Res Paediatr. 2011; 76(6):428-33.
  • Consortium on the Management of Disorders of Sex Development. Handbook for Parents. ISNA; 2006.
  • Winterborn MH, France NE, Raiti S. Incomplete testicular feminization. Arch Dis Child. Dec 1970; 45(244):811-2.

Media References

  1. Androgen receptor 3-d model, CC BY 3.0