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Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS) is a disorder of sex development that impairs the ability of males* (46 XY) to develop the expected male genitalia (penis and scrotum) and other male body features, including body and facial hair and parts of the reproductive tract (epididymis, prostate, vas deferens and seminal vesicles). AIS is caused by the body not being able to respond to androgens (male sex hormones, including testosterone). This is due to variants in the androgen receptor (AR) gene on the X chromosome. AR is what the body uses to recognize testosterone in the blood and respond accordingly (like by forming the penis during fetal development, or by growing facial hair during puberty). In males with AIS, the testes (i.e. testicles or “balls,” the testosterone-producing reproductive organs of males) develop normally because of genes on the Y chromosome. But, the testes will typically be undescended, meaning they are not seen or felt on the outside of the body in a scrotum and instead remain higher up inside the abdomen. Undescended testes still produce high levels of testosterone like other males. However, in patients with AIS, the body can’t sense that testosterone and acts like it isn’t there, so male features do not develop normally. Instead, patients have varying degrees of ambiguous genitalia and features typical of females1,2.

Depending on the specific mutation in the AR gene, males with AIS will have different amounts of retained AR function– some will have no AR in the body and will not be able to respond to testosterone at all, while some will have partial expression of the receptor and still be able to respond to testosterone a little bit. Because of this variability, the disease will look different in different people, and patients with AIS are often placed in one of 3 groups: complete AIS (CAIS), partial AIS (PAIS), or mild AIS (MAIS). Patients with CAIS have the most severe disease, usually appearing completely female, including their genitalia (they will externally have a vagina), and will be assigned the female sex at birth. These patients will later develop breasts and will have minimal or no body hair, pubic hair or hair under their armpits. PAIS is a spectrum of severity within itself, with patients usually having genitalia that appears neither clearly male nor clearly female, and their sex assignment at birth may vary. MAIS involves a lot of retained AR gene function, so the phenotype of disease is less severe. Patients with MAIS usually have male genitalia but may develop breasts (gynecomastia) during puberty and may experience challenges with fertility1,2.

Importantly, even in male patients with CAIS, female reproductive organs (including the uterus and ovaries) will not develop. That is because genes on the Y chromosome cause testes to form instead of ovaries, and testes produce a hormone called AMH (in addition to testosterone) which prevents the maturation of the uterus and uterine tubes. So, while patients with AIS may appear to have female bodies from the outside, they will not have all of the internal female organs, and will not be able to menstruate (have a period) or become pregnant.

 

Females with AIS

This section will discuss the effects of AIS on individuals who are chromosomally female, meaning they have two X chromosomes (karyotype 46 XX)*.

Because testosterone is not an essential part of the development of a female fetus, females with variants in the AR gene on one of their X chromosomes (heterozygotes) will not develop AIS. Because females have no Y chromosome, they develop ovaries instead of testes, and the absence of AMH allows their uteruses and uterine tubes to continue growing normally. While females do make and use smaller amounts of androgens (like testosterone) to develop body, pubic and armpit hair and to support normal ovulation and fertility, the importance of androgens is less significant in females compared to males. And, since females have two X chromosomes and thus two copies of the AR gene, most females (90%) have sufficient AR function and show no signs or symptoms of the disease3. The 10% of females who do show signs have only subtle features, including asymmetric, sparse or delayed body hair growth4,8. There is a theoretical risk for females with AR variants to also have impaired fertility (see below), however there is no clear clinical evidence that this occurs in humans.

Several studies have looked at female mice who have one or two AR variant(s), and they observed that in both cases, the mice had reduced fertility, with smaller litter sizes and more difficulty becoming pregnant compared to mice with two functional AR genes4,5. This is due to a combination of decreased ovulation, impaired follicular development, and impaired ability for an embryo to implant and be maintained properly throughout pregnancy5,6. These are all processes that are known to involve androgens, so the impaired response to androgens is a logical reason for these deficits to occur7. Even though these studies were in mice rather than humans, they help us to predict what effects AR mutations might have on fertility in females. That said, infertility or impaired fertility have not been consistently reported in females carrying AR variants as of yet.

*Please note that in this description, “male” and “female” refer to the chromosomes that individuals have, with male meaning karyotype 46XY and female 46XX, rather than the phenotype (body features) that they express. Many individuals who are chromosomally male but have CAIS or PAIS will be assigned the female sex at birth based on appearance and sex expression and will be raised with female gender. Many patients will not even know about their condition until later in life when noticing amenorrhea (lack of a menstrual period) or infertility. Decisions surrounding gender identity should be made individually, with personalized consideration of social and health-related priorities.

This page was last updated in August, 2026. Please note that research into females with this condition is limited. As a result, percentages and prevalence rates may not be accurate or widely applicable. Decisions regarding your own health should be made in consultation with your medical provider.

  1. Hughes IA, Davies JD, Bunch TI, Pasterski V, Mastroyannopoulou K, MacDougall J. Androgen insensitivity syndrome. The Lancet. 2012;380(9851):1419-1428. doi:10.1016/S0140-6736(12)60071-3
  2. Wang C, Tian Q. Molecular pathogenesis, diagnosis, and management challenges in complete androgen insensitivity syndrome. Front Endocrinol. 2025;16:1600343. doi:10.3389/fendo.2025.1600343
  3. Gottlieb B, Trifiro MA. Androgen Insensitivity Syndrome. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. University of Washington, Seattle; 1993. Accessed August 5, 2026. http://www.ncbi.nlm.nih.gov/books/NBK1429/
  4. Walters KA, Allan CM, Jimenez M, et al. Female Mice Haploinsufficient for an Inactivated Androgen Receptor (AR) Exhibit Age-Dependent Defects That Resemble the AR Null Phenotype of Dysfunctional Late Follicle Development, Ovulation, and Fertility. Endocrinology. 2007;148(8):3674-3684. doi:10.1210/en.2007-0248
  5. Characterizing the neuroendocrine and ovarian defects of androgen receptor-knockout female mice | American Journal of Physiology-Endocrinology and Metabolism | American Physiological Society. Accessed August 5, 2026. https://journals.physiology.org/doi/full/10.1152/ajpendo.00263.2013?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
  6. Zhao Y, Xu J, Liu C, et al. Functional androgen signaling pathway potentiates maternal-fetal interactions—— implantation, placentation and early pregnancy maintenance. Placenta. 2026;180:42-49. doi:10.1016/j.placenta.2025.07.073
  7. Astapova O, Minor BMN, Hammes SR. Physiological and Pathological Androgen Actions in the Ovary. Endocrinology. 2019;160(5):1166-1174. doi:10.1210/en.2019-00101