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  Partial Androgen Insensitivity
Authors: Claude Migeon, M.D., Amy Wisniewski, Ph.D. Last modified: October 10, 2001


  • Androgen Insensitivity Syndrome (AIS) refers to the condition in which an individual produces androgens (like testosterone), yet their body is unable to respond to these hormones.
  • AIS is due to a mutation of the androgen receptor gene; this gene is located on the X chromosome (X-linked disorder). A family history may reveal other affected individuals on the maternal side.
  • Identification of an androgen receptor (AR) gene mutation is the gold-standard for diagnosing AIS.
  • AIS exists in both complete (CAIS) and partial (PAIS) forms.
  • Production of testosterone and LH are normal or elevated. Despite this, male duct development is limited and the external genitalia are under-masculinized.
  • Production of Mullerian inhibiting substance (MIS) is normal or elevated, therefore female duct development is suppressed.


  • The frequency of PAIS is 1 out of 30,000 individuals with a 46,XY karyotype.
  • At puberty, patients reared male can develop gynecomastia.
  • As a result of their genital ambiguity at birth, patients reared male or female are at risk for sexual dysfunction.
  • If the gonads remain in the abdomen, a high risk for development of testicular tumors exists.


  • At birth, infants with PAIS present with varying degrees of ambiguity of male external genitalia.
  • At puberty there can be a small penis with normal size testes.
  • Gynecomastia.
  • Reduced sexual hair.
  • Azoospermia and infertility.


  • At birth a full work-up for ambiguous genitalia must be obtained.
  • Obtain serum electrolytes daily.
  • At Day 1 or 2 of life, obtain a karyotype and measure plasma androstenedione, testosterone and dihydrotestosterone.
  • At Day 3 or 4 measure plasma 17-hydroxyprogesterone and 17-hydroxypregnenolone.
  • At Day 5 to 6, obtain a genitogram.
  • At Day 7 to 8 measure MIS and to perform DNA studies.
  • At Day 9 to 10 repeat androstendione, testosterone, dihydrotestosterone and 17-hydroxyprogesterone.
  • If the karyotype is 46,XY along with normal to elevated levels of testosterone, dihydrotestosterone and MIS a presumptive diagnosis of AIS can be made.
  • 17-hydroxyprogesterone and 17-hydroxypregnenolone production should be normal for age.
  • Once a presumptive diagnosis for AIS is established, this can be confirmed by AR gene studies.
  • CAH due to 3B-hydroxysteroid dehydrogenase deficiency
  • 5alpha-reductase deficiency
  • Partial gonadal dysgenesis
  • Steroidogenic enzyme defects associated with testosterone production
  • Leydig cell hypoplasia
  • Timing defect
  • True hermaphroditism


  • 46,XY karyotype
  • An AR gene mutation.
  • In newborns and adults, concentrations of androstendione, testosterone, dihydrotestosterone, LH and FSH are in the normal male range or higher.
  • MIS concentrations are in the normal male range or higher.
  • At birth, consideration for raising the infant as female is made if the stretched penile length is equal to or less than 1.9 cm (mean - 2.5 SDs) and perineo-scrotal hypospadias exists.
  • In less severe cases of genital ambiguity, male rearing can be successful.
  • When deciding sex of rearing, parents must be completely informed about sex differentiation and abnormalities that can occur (
  • Parents and patients should have a realistic expectation for the difficulties and outcome of medical and sugical treatment they will be offered regardless of sex of rearing.
  • Although patients with PAIS reared male produce their own testosterone, they can be given additional testosterone in the attempt to optimize masculinization.
  • People with PAIS vary greatly in their responsiveness to testosterone treatment due to their insensitivity to androgens. Therefore testosterone treatment can be unsuccessful.
  • If the testes are removed due to the inability to correct cryptochordism, life-long testosterone treatment may be required.
  • Under-masculinized genitalia requires surgical correction for hypospadias in patients reared male.
  • If the testes were removed due to the inability to correct cryptochordism, implantation of prosthetic testes is recommended.
  • In additon to surgical reconstruction of their genitalia, boys and men with PAIS may require surgical correction for gynecomastia.
  • Patients benefit greatly from education and counseling regarding their condition. Education allows for patients and parents to make informed medical and surgical choices .
  • Many men and women with PAIS benefit from counseling when dealing with infertility, sexual dysfunction and genital surgery.
  • It is important that people affected by PAIS seek medical, surgical and psychological care from those who have experience treating this condition.
  • Depending on the degree of genital ambiguity, female sex of rearing may be optimal and this option should therefore be presented to patients and parents.
  • Because AIS is an X-linked heritable condition, genetic counseling should be considered for women whose families are affected by this type of abnormal sex differentiation.
  1. Migeon CJ, Wisniewski AB and Gearhart JP ;  Abnormal Sex Differentiation: A Guide for Patients and Their Families ;

    This online guide explains androgen insensitivity syndrome (AIS) within the context of male sex differentiation.

  2. Migeon CJ, Brown TR and Fichman KR ;  Androgen Insensitivity Syndrome ;  (Ed. N Josso) The Intersex Child. Pediatric and Adolescent Endocrinology, Volume 8. Karger, Basel Switzerland, 1981.

  3. Brown TR and Migeon CJ ;  Mechanism of Action of Androgens: Androgen Receptors ;  (Ed. MG Forest) Androgens in Childhood. Pediatric and Adolescent Endocrinology, Volume 19. Karger, Basel Switzerland, 1989.

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