There are multiple causes of androgen insensitivity syndromes (AIS).
With partial androgen insensitivity, the body has limited sensitivity to androgens.
With complete androgen insensitivity, the body can’t respond to androgens at all.
Astrakan Images / Getty Images
There are also mild androgen insensitivity syndromes (MAIS).
Androgen insensitivity syndromes fall under the broader category of disorders of sexual development or differences of sexual developmentDSDs.
These conditions are also known as being intersex.
Although that term has fallen out of favor, intersex is easier for some people to understand.
People with DSDs have physical characteristics that are between male and female.
Androgen insensitivity syndromes are DSDs because androgen insensitivity affects the sexual development of the body.
People are generally taught that sex is determined by chromosomeseither people have male XY chromosomes or female XX chromosomes.
However, it isn’t that simple.
Sex is determined not just by the presence of particular sex chromosomes but also by their function.
It’s also determined by how the body responds to those sex hormones.
For example, a person can be born with XY chromosomes but develop as a female.
How does that happen?
When someone has complete androgen insensitivity syndrome.
Sex hormones are also known as steroid hormones, and they includeestrogenand testosterone.
The masculinizing group of steroid hormones is known as androgens (andro- is the Greek prefix for male).
This category consists of testosterone,dihydrotestosterone (DHT), androstenedione, anddehydroepiandrosterone (DHEA).
When someone has androgen insensitivity, they are less responsive to the signals for maleness.
Androgen insensitivity is a relatively rare disease.
It is thought to affect around 13 out of every 100,000 individuals.
Complete androgen insensitivity affects one in every 20,000 to 50,000 females.The prevalence of partial androgen insensitivity is not known.
Symptoms
Historically, androgen insensitivity syndrome was known astesticular feminization syndrome.
This is because it often was not discovered until seemingly normal females did not undergomenarche.
The symptoms of androgen insensitivity depend on the key in.
Individuals with complete androgen insensitivity are XY women.
Because their bodies are completely unresponsive to testosterone, they are born with normal-appearing female genitalia.
As such, complete androgen insensitivity may not be diagnosed until puberty.
When these girls reach puberty, they do not menstruate.
This is because they do not have a uterus.
Because they do not have a uterus, they are unable to conceive or carry a pregnancy.
They may be taller than other girls but generally have normal breast development.
The symptoms of partial androgen insensitivity are more variable.
At the time of birth, individuals may have genitals that appear almost completely female to almost normally male.
They can also appear anywhere in between.
They may also experience fused labia at the time of puberty.
To understand this, it helps to know that the labia and scrotum are homologous structures.
This means they originate from the same tissue.
However, they develop differently depending on hormone exposure.
The penis andclitorisare also homologous structures.
Men with mild androgen insensitivity often develop normally in childhood and adolescence.
However, they may experiencegynecomastiamale breast growth.
They may also have reduced fertility.
Causes
Androgen insensitivity is resulting from mutations in the androgen receptor gene.
As such, it is an inherited condition that runs in families as an X-linked trait.
That means it occurs on the X chromosome and follows the maternal line.
Over one thousand mutations have been identified to date.
Diagnosis
The initial diagnosis of androgen insensitivity is usually because of symptoms.
Often, complete androgen insensitivity is not diagnosed until puberty.
Partial androgen insensitivity may be diagnosed much earlier.
If the genitals are clearly ambiguous at the time of birth, a number of tests may be done.
These include akaryotypeor a count of the chromosomes.
Hormone levels may also be tested.
In adult men, a semen analysis may be done.
During puberty, testosterone and LH levels are usually normal or slightly elevated for individuals with PAIS.
However, individuals with CAIS will have very high levels.
This is because hormone production is controlled bynegative feedback loops.
In individuals with CAIS, there is no mechanism for feedback.
Other tests may include biopsying the gonads.
In all individuals with androgen insensitivity, they will have testes rather than ovaries.
It is also possible to look for mutations in the androgen receptor genes.
However, while this is a reasonably reliable marker for CAIS, it is not for PAIS.
Only a fraction of mutations that cause PAIS has been identified to date.
Treatment
Individuals with complete androgen insensitivity usually do not need any treatment prior to puberty.
The exception is if their testes cause discomfort or if they can be felt in the abdominal wall.
After puberty, the testes are usually removed.
This reduces the risk of young women developing testicular cancer in adulthood.
In addition, some may need to undergo dilation to increase vaginal depth, similar to withMRKH.
Treatment for partial androgen insensitivity is more variable.
Historically, individuals with ambiguous genitalia were subject to genital surgeries.
These surgeries usually were designed to make the genitals appear more feminine.
However, they had permanent effects on individuals' ability to experience sexual satisfaction.
Therefore, these surgeries are no longer used as the default.
Individuals who have a penis are generally assigned and maintain a male gender identity.
Individuals with AIS may also be given hormone replacement therapy, usually in the form of estrogen.
This is because sex hormones play a role in numerous areas of health, including bone health.
Individuals with PAIS may have sufficient bone development with their testicular testosterone.
Coping
Individuals with androgen insensitivity generally have good physical outcomes.
However, androgen insensitivity can be associated with psychosocial problems.
Educating the person with age-appropriate information about their condition is recommended.
Young people diagnosed with androgen insensitivity may have questions about their gender and sexual identity.
In addition, it can be difficult for any individual to deal with infertility.
For some people, learning that they will never be able to have biological children can be devastating.
They may question their femininity and/or masculinity.
They may also wonder if they can ever have a successful relationship.
There are a number of support groups available around the country, both online and in person.
you might take time to do your own research and make your own decisions.
People with androgen insensitivity are generally no more or less healthy than anyone elsethey’re just a little different.
2015 Jun;12(4):373-87.
2012 May;33(5):887-94.
Kon AA.Ethical issues in decision-making for infants with disorders of sex development.
2015 May;47(5):340-3.
Mendoza N, Motos MA.Androgen insensitivity syndrome.
2013 Jan;29(1):1-5.
