Complete, mild, or partial androgen insensitivity syndrome (CAIS, MAIS, PAIS)

Complete androgen insensitivity syndrome (CAIS) is a condition whereby cells are unable to respond to androgens (testosterone). Genital tissue that would ordinarily become masculinised through the action of testosterone in a developing 46, XY foetus remains the default feminine.^​1​

Additionally, at puberty, secondary male characteristics (pubic hair, voice drop, genital growth, etc.) do not occur.

People with CAIS are genetically male – 46, XY (instead of 46, XX) – but in every other way, they are female. 

When an egg is fertilised, the sperm determines the child’s chromosomes, which is already decided by the time we start growing in the womb. All babies are, by default, female.

CAIS interrupts the growing process when the foetus would ordinarily change from the default girl into a boy. What you end up with in CAIS is a genetic female.

People who have 46, XY chromosomes are almost always heterosexual with female gender identity. It is not thought to be related to transgenderism, though it is an understudied population.

The other variants of CAIS – partial or mild androgen insensitivity (PAIS and MAIS) – can result in body variations, including the full spectrum of genital appearance. CAIS, MAIS and PAIS affect genital appearance only.

Terms to know when talking CAIS

46, XY – genetic male

46, XX – genetic female

DSD – Differences in Sexual Development

Phenotypical – characteristics of, in this case, body shape, voice, and general body features CAIS can occur in genetic females (46, XX). However, the genitals and sexual development are not significantly affected since genetic females don’t have the same androgen dependency.

The incidence of CAIS is unknown, but one estimate puts it at one in every 20,400 live 46, XY births. That is, one in every 20,400 genetically male live births. This process occurs due to the SRY gene’s influence on the Y chromosome.

Types of androgen insensitivity syndrome

There are three types of androgen insensitivity syndrome split up depending on the degree of genital masculinisation. AIS is the largest single cause leading to 46,XY under-masculinisation.

1. Complete androgen insensitivity syndrome (CAIS) – external genitalia is that of a typical female, with no signs of masculinity
2. Mild androgen insensitivity syndrome (MAIS) – external genitalia is that of a typical male
3. Partial androgen insensitivity syndrome (PAIS) – external genitalia is partially, but not fully, masculinised, including male appearance, but small penis, micropenis, large clitoris, and other flesh development differences

Diagnosis of CAIS

CAIS is not suspected unless periods don’t arrive or an inguinal hernia (a hernia in the soft, large V space that surrounds the pubic mound) presents itself before puberty.^​2,3​

Up to two per cent of children with inguinal hernias have CAIS. CAIS can be diagnosed in utero using a karyotype from the foetus and comparing it to the external genitalia of the foetus during a prenatal ultrasound.

CAIS – what it looks like in real life

These genetic males are born as a 46,XY karyotype but appear entirely female. Symptoms do not appear until puberty, which could be somewhat delayed, though they appear pretty typical except for the conspicuous absence of menstrual periods (primary amenorrhoea).^​4​

This means someone may not find out until they are between 15 and 18 years old – a confusing time to find out you should have, technically, been a boy. Pubic hair may also be scant or absent.

A third of all people with CAIS do not develop armpit hair. The labia and clitoris can be somewhat underdeveloped. Vaginal depth is variable and generally appears typical but could be on the short side.^​5​

People with CAIS do not have ovaries, a uterus, fallopian tubes or a cervix but do have testes since the testes do not need androgens to develop. This means that no eggs exist, and therefore biological children are impossible.

The fallopian tubes, uterus and the upper portion of the vagina (the Müllerian system) most often regress due to a hormone that stems from the testes, anti-Müllerian hormone (from the Sertoli cells).^​6​ This means those affected by CAIS most often do not have fallopian tubes, a cervix, or a uterus, and the vagina ends in a pouch.

Sometimes, this process is incomplete (in a third of cases), and there will be remnants of these organs. Occasionally, a person with fully developed Müllerian structures is reported. Each case is reasonably unique in this respect. 

The testes are often found in different locations, which could spark the discovery of this condition. Testes found in affected people are atrophic (wasting away) once removed.^​7​

The testosterone produced by these testes can’t be utilised directly, since the mutant androgen receptor that caused the condition in the first place is a characteristic of this state, and isn’t usable to a great degree.

Instead, the testosterone is converted into oestrogen, causing the feminisation of the body and resulting in the typical female appearance.^​8​

The testes produce immature sperm; however, they don’t get an opportunity to mature – spermatogenesis relies on androgens.

The epididymides, vas deferens and seminal vesicles don’t exist, but in 30 per cent of cases, these structures can partially develop. This development depends on the mutant causing the CAIS.

The prostate never develops and remains in the female form (Skene’s glands).

The whole body is affected by CAIS, here’s how

Other differences in people with CAIS are slightly longer limbs and larger hands, feet, and teeth due to greater stature than those unaffected. People with CAIS usually never suffer from acne (often caused by androgens), have well-developed breasts, and more dysfunction of moisture-producing glands (meibomian gland) – dry eyes, light sensitivity, etc.

Tissues throughout the body, including the bones, are affected. Bone mineral density can decrease, with some suggesting the late timing of the gonadectomy (removal of the testes) and a lack of oestrogen supplementation are the culprit, however recent research has not supported this. New hypotheses suggest that androgens play more of a role in bone mineralisation than previously thought.^​9​

CAIS is associated with increased gonadal tumours if the testes are left in the body. This risk increases with age – 33 per cent at age 50, compared with just 3.6 per cent at age 25.^​10​

Childhood gonadal tumour incidence is low. Longevity is not thought to be associated with CAIS, meaning anyone with CAIS, PAIS, or MAIS can expect to live a long and healthy life, with all other things being equal.

Fertility outcomes in CAIS

Most people with CAIS are infertile, however in mild and partial forms, this isn’t always true.^​11,12​

Psychological outcomes in CAIS

CAIS is associated with psychological difficulties, at least partially due to parents not understanding how to manage their child’s very particular situation.^​13​

Long-term counselling for parents and kids is recommended. It can be challenging to find out that you aren’t ‘normal’, you may never have biological children, ‘ordinary’ sex may be difficult, and that your genitals (and insides) may look different to everyone else’s.

Feelings are intense, and the grieving process must be respected. Acceptance is the goal, and learning self-love is critical. while easy to say and not easy to do, counselling can help to redirect your mental and emotional energies into things that help you feel good.

Support is critical, and there are forums and forums full of people with CAIS, PAIS and MAIS. Find them. Dance.

What else could it be?

Swyer syndrome or Müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH) may be suspected.

CAIS and Swyer syndrome are both associated with the same 46, XY karyotype, so it is easy enough to rule out MRKH. MRKH means a genetic female who looks like a genetic female.

Management strategies for CAIS outcomes

Management is the only real option, and that means controlling any negative symptoms. Management may include sex assignment, genitoplasty, gonadectomy, hormone replacement therapy, vaginal dilation, and genetic and psychological counselling.

Gender assignment and identification in CAIS

People with CAIS are raised as girls – they almost always have a heterosexual female gender identity, and the incidence of homosexuality in those with CAIS is understood to be less than in women without CAIS. Rarely, male gender identity has been reported.

Splitting the concept of gender and sex is critical – sex is usually about physical attributes, whereas gender is based on our self-concept and identification and the role we play in our lives.^​14​

There are currently no predictors of someone’s eventual gender identity, with PAIS being more complex for gender identity than the CAIS or MAIS.

Sexual activity for people with CAIS

An improperly formed or shallow vagina (vaginal hypoplasia) or a missing vagina (vaginal agenesis) is common and can cause painful sexual problems (dyspareunia) and issues with penetration.^​15​

Dilation can be used to help stretch out the vaginal tissue, even in the most severe cases. Dilation can be uncomfortable or painful, so compliance is an issue.

Typically the Vecchietti procedure has been used, but new, less invasive techniques are now more popular. Dilation should not be used prior to puberty.

Hormone replacement therapies in CAIS

Androgen replacement has been found to increase a sense of wellbeing in those who have had their testes removed, and women taking oestrogen therapies experience less bone loss.^​16​

The neovagina in CAIS

A neovagina is a vaginoplasty surgical procedure using skin grafts, a segment of bowel, and other tissues to create a vagina for sexual function. It is a big operation, but is of late becoming more and more successful and satisfying. Neovaginas have their own type of microbiome.

Psychological challenges of CAIS

The psychological consequences can be hefty, since infertility and sexual problems can be heavy burdens to carry. With solid psychological and physical support, however, people with CAIS can be perfectly content.^​17​

V-spot Probiotic Vaginal Suppository

Rated 5.00 out of 5

(1) USD $34.95

Specially formulated probiotic for vaginal application to promote a healthy vaginal microbiome.

Add to cart

BV Vaginal Pessary

Rated 5.00 out of 5

(9) USD $44.95

Naturopath-developed 100% natural, effective BV treatment.

Add to cart

Killing BV: Vagina Treatment Program

Rated 4.88 out of 5

(8) USD $9.95 Original price was: USD $9.95.USD $0.00Current price is: USD $0.00.

Unique, comprehensive BV, AV and 'mystery bad vag' treatment guide, one-of-a-kind system, with effective, innovative treatments.

Get it free