• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Partial Androgen Insensitivity Syndrome


Last updated: August 13, 2019
Years published: 1991, 2005, 2019


NORD gratefully acknowledges Tiffany Yip, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.

Disease Overview


Partial androgen insensitivity syndrome (PAIS) is genetic condition that affects the sexual development of a male fetus. During pregnancy, male fetuses with PAIS are unable to properly respond to male sex hormones (androgens). As a result, this affects the development of the genitals. The appearance of the genitals may vary from person to person. Some males have an unusually small penis (microphallus), undescended testes, hypospadias (urethra located on the underside of the penis), and/ or bifid scrotum (scrotum split in two). Others may have more female-appearing genitals and physical features, including a large clitoris (clitoromegaly), male breast development (gynecomastia), undescended testes, and/ or fusion of the labia. Individuals with PAIS typically have infertility. PAIS is caused by a change in the AR gene, which is located on the X chromosome. It is inherited through an X-linked recessive pattern and typically affects males. It is recommended that parents and caretakers work with an experienced healthcare team to evaluate a child with PAIS before assigning their sex. If the individual is reared as male, they may be given testosterone therapy to improve fertility and surgeries to repair structures of the penis and to reduce the size of the male breasts. If the individual is reared as female, they may be offered surgery to remove the male reproductive organs after puberty, followed by estrogen (female sex hormone) therapy.


Androgen insensitivity occurs when a person’s body cannot respond properly to male sex hormones (androgens) during pregnancy. Partial androgen insensitivity syndrome (PAIS) belongs to a group of conditions that involves androgen insensitivity, including complete androgen insensitivity syndrome (CAIS) and mild androgen insensitivity syndrome (MAIS). The androgen insensitivity syndromes have historically been called “testicular feminization,” based on the appearance of the genitals. However, because the group of conditions vary from person to person based on one’s response to androgens, it is now referred as “androgen insensitivity.”

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  • PAIS
  • testicular feminization
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Signs & Symptoms

Characteristics of partial androgen sensitivity syndrome vary from person. Each person with PAIS is unique and may not have the same features.
Some people with PAIS may have more female-appearing features. For example, some can be born with female-appearing genitals but may have an enlarged clitoris (clitoromegaly) or fusion of certain areas of the labia. In addition, some individuals may be born with openings of a female-appearing urethra (duct where urine is released from the bladder to outside the body) and vagina. However, individuals with PAIS do not have female sex organs such as a uterus and ovaries. Some people with this condition may have undescended testes, in which one or both testicles are not able to descend completely by puberty. Because they do not have ovaries and may have issues with the development of the testes, many people with PAIS are infertile, because they produce no or very little sperm. Also, some individuals with PAIS may develop breasts (gynecomastia) during puberty.

Other people with PAIS may have more male-appearing features. For example, some may develop a penis. Some affected males may be born with a small penis, which is usually less than 1 cm, and may look similar to a clitoris. Those who develop a penis may be born with a feature called hypospadias, in which the opening of the penis is on the underside. As a result, boys with hypospadias may have issues urinating in certain directions. During puberty, people with PAIS may also develop a bifid scrotum, in which their scrotum area may separated by a groove into two parts.

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Partial androgen insensitivity syndrome is a genetic condition that is inherited in an X-linked recessive pattern. The gene related to partial androgen sensitivity syndrome is the AR gene, which is located on the X chromosome. When people have a change in the AR gene, their bodies may have issues producing androgen receptors, which are structures in cells that allow the body to properly respond to androgens (male sex hormones). Because of problems with the androgen receptors, people with changes in the AR gene have the characteristics of partial androgen sensitivity syndrome.

Chromosomes are located in the nucleus of human cells and carry the genetic information (DNA) for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.

X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an altered gene he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

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Affected populations

Partial androgen sensitivity syndrome is very rare in the general population. 1 in 99,000 male infants are born with one of the several androgen sensitivity syndrome types, including PAIS. PAIS only affects males, but females can be carriers for this genetic condition.

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Because features of partial androgen insensitivity syndrome vary from person to person, there are no standard diagnostic procedures for PAIS. PAIS may be suspected based on clinical features such as female-appearing genitals, absence of female sex organs (ovaries and the uterus), and issues with sperm production. Some laboratory results can help with the diagnosis. For example, if the patient has some physical features of PAIS and is confirmed through genetic testing to have XY chromosomes, it would further support the possibility of PAIS. Some other lab results that could help with diagnosis include having normal or high levels of testosterone (produced by testes) and luteinizing hormone (produced by pituitary gland).

To further confirm a diagnosis of PAIS, genetic testing can be done to look for changes in the AR gene. Sometimes genetic testing cannot find any changes in the AR gene. If this is the case, an androgen binding assay may be performed to measure androgen receptors. This assay can also confirm a diagnosis of PAIS.

Clinical Testing and Work-Up
Once a patient is diagnosed with PAIS, it is important for the patient to be evaluated by medical providers who specialize in disorders of sex development. Some of these specialists may be from fields of urology, gynecology, clinical genetics, psychiatry, psychology, and endocrinology.

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Standard Therapies

Sex assignment is one of the major tasks that is performed after diagnosis of PAIS. Parents should work with their healthcare team in order to make an informed decision about sex assignment. If the patient is reared as a female, then she may receive surgery to remove the male sex organs. She may also be given estrogen (female sex hormone) therapy after puberty. If the patient is reared as a male, then he would be given testosterone therapy and surgery to repair the male sex organs and remove the breasts (gynecomastia).

Some people with PAIS have sex assignment at birth, while others may have it after puberty. This decision is usually based on the circumstances and input of the family, the patient, and medical providers.

Genetic counseling is recommended for patients and their families.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Hughs IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J, Androgen insensitivity syndrome. The Lancet. 2012;380:9851:1419-1428.ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(12)60071-3. http://www.sciencedirect.com/science/article/pii/S0140673612600713

Morcel K, Camborieux L, Programme de Recherches sur les Aplasies Müllériennes (PRAM), Guerrier D. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet Journal of Rare Diseases. 2007;2:13. doi:10.1186/1750-1172-2-13.

Manzoni, G., Bracka, A., Palminteri, E. and Marrocco, G. (2004), Hypospadias surgery: when, what and by whom?. BJU International, 94: 1188–1195. doi:10.1046/j.1464-410x.2004.05128.x

Brinkmann, A. O., Jenster, G., Ris-Stalpers, C., Van Der Korput, J. A. G. M., Brüggenwirth, H. T., Boehmer, A. L. M., & Trapman, J. (1995). Androgen receptor mutations. The Journal of steroid biochemistry and molecular biology, 53(1), 443-448.

Nimkarn S, Gangishetti PK, Yau M, et al. 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia. 2002 Feb 26 [Updated 2016 Feb 4]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1171/ Accessed March7, 2019.

Gottlieb B, Trifiro MA. Androgen Insensitivity Syndrome. 1999 Mar 24 [Updated 2017 May 11]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1429/ Accessed March 7, 2019.

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