Introduction:
Complete androgen insensitivity or complete androgen insensitivity syndrome is a type of androgen insensitivity syndrome with the complete inability of the body to respond to the androgens (male sex hormones). In this condition, there is a feminization of the external genitals at birth, abnormal development of the secondary sexual characters at puberty, and infertility.
Despite the existence of a Y chromosome, those with complete androgen insensitivity have a normal outward female habitus. The gonads, having been transformed into testicles rather than ovaries in an earlier separate process also initiated by their Y chromosome, will remain undescended in the region where the ovaries would have been, and the vaginal cavity will be shallow.
What Is Androgen Insensitivity Syndrome?
Androgen insensitivity syndrome (AIS) is a genetic condition that affects sexual development before birth and during puberty. People born with this condition are genetically male but have the physical traits of a female or traits of both males and females. Androgen insensitivity syndrome typically makes the person infertile; they will not be able to get pregnant or impregnate their partner.
What Are the Types of Androgen Insensitivity Syndrome?
There are two types of androgen insensitivity syndrome, and they are as follows:
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Partial Androgen Insensitivity - In the condition, the cells are partially responsive to the androgens. This type is also known as the Reifenstein syndrome, and it occurs at the same rate as the complete androgen insensitivity syndrome.
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Complete Androgen Insensitivity- In this condition, the cells are completely unresponsive to the androgens.
What Is Complete Androgen Insensitivity?
Complete androgen insensitivity is a condition characterized by the inability of the cells to respond to the androgen hormones. This unresponsiveness of the cells to the androgens prevents masculinization of the male genitals in the developing fetus, along with preventing the development of male secondary sexual characters during puberty.
However, there is a development of female genitalia and sexual development. In other words, complete androgen insensitivity can be defined as a condition in which the child is genetically male but develops female sexual characters.
What Are the Other Names of Complete Androgen Insensitivity?
There are multiple other names by which complete androgen insensitivity is known. They are:
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Testicular feminization.
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Complete androgen resistance syndrome.
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Androgen receptor deficiency.
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Dihydrotestosterone receptor deficiency.
What Causes Complete Androgen Insensitivity Syndrome?
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During development, all human fetuses grow in the same way, with both the female system (Mullerian duct system) and the male system (Wolffian duct).
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In a male fetus that is not affected by complete androgen insensitivity, masculinization begins during the seventh week of pregnancy. The male system is promoted, and the female system is suppressed, and in the case of a developing female fetus, the opposite happens. This process is triggered by androgen produced by the genitals. When an egg fertilizes, each parent contributes a sex chromosome. XX chromosomes from females and XY chromosomes from a male.
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In the case of complete androgen insensitivity syndrome, there is a mutation in the androgen receptor (AR) gene. This gene is responsible for making a protein known as the androgen receptor.
How Rare Is Complete Androgen Syndrome?
Studies have estimated that complete androgen syndrome occurs in one in 20,400 to one in 99,000 individuals.
Is Complete Androgen Insensitivity Inherited?
Complete androgen insensitivity syndrome is hereditary, which means it is passed down from the parents to their children. It is inherited in an X-linked recessive pattern (because the mutated gene is present on the X chromosome). Men are more frequently affected by this condition because, in genetic males, one altered copy of the gene in each cell can cause the condition. Whereas in genetic females, this mutation must be present in both copies of the gene.
Women who carry the androgen insensitivity affected genes have a one in four chance of giving birth to a girl who is unaffected but can pass the altered gene to the next generation. one in four chances of an unaffected boy, one in four chances of a girl who is unaffected and does not carry the altered gene as well, and lastly, one in four chances of having a child with androgen insensitivity syndrome.
What Are the Symptoms of Complete Androgen Insensitivity?
An individual affected by the complete androgen insensitivity syndrome is generally born structurally as a female. But the symptoms of this condition do not reflect until puberty. Mentioned below are the symptoms of complete androgen insensitivity:
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No signs of genital masculinization.
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Infants born with this condition will be born female, but they will lack a uterus, fallopian tubes, and ovaries.
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Absence of menstruation even after the age of puberty.
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Absent terminal hair.
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Development of breasts at the age of puberty.
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Normal external genitalia with underdeveloped labia and clitoris.
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Vaginal depth is less than that of an unaffected female.
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Absence of ovaries and presence of atrophic testes.
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Failure of one or both testes to descend into the scrotum.
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Little to no pubic hair and underarm hair.
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The vagina ends blindly into a pouch.
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Longer limbs.
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Larger hands, feet, and teeth.
How Is Complete Androgen Insensitivity Diagnosed?
The diagnosis of complete androgen insensitivity is made by:
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Missing menses even after the age of puberty has passed is an important clinical sign that helps in the diagnosis.
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The genetic abnormality is detected in the womb with the help of amniocentesis (a process of prenatal diagnosis of chromosomal abnormalities, sex, and fetal infection with the help of amniotic fluid).
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The baseline luteinizing hormone and testosterone measurement is used to check the spontaneous neonatal testosterone surge. This surge is absent in the case of an infant affected by complete androgen insensitivity.
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The presence of the Y chromosome is checked to rule out the diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome. This is done with the help of fluorescence in situ hybridization.
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The diagnosis is confirmed when the androgen receptor gene mutation is revealed.
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Apart from these, blood examinations are done to check for hormone levels, a pelvic ultrasound may be used to study the sexual organs in the individual, and genetic tests are done.
How Is Complete Androgen Insensitivity Treated and Managed?
Currently, only symptomatic treatment is available for the management of complete androgen insensitivity. Methods of management include:
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Sex Assignment and Sexuality- Most individuals born with complete androgen insensitivity are raised as female because they are born with female physical characteristics.
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Dilation Therapy- Underdeveloped vagina associated with complete androgen insensitivity can be treated using a non-surgical pressure dilation method. However, this procedure should not be performed before puberty.
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Gonadectomy- Individuals affected with complete androgen insensitivity will have to undergo gonadectomy (of undescended testes) to prevent cancer risks.
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Hormone Replacement Therapy- Complete androgen insensitivity is treated with estrogen replacement therapy after puberty.
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Counseling- In a lot of cases, the diagnosis of complete androgen insensitivity syndrome is hidden from the affected individuals and their families. Psychological assistance is essential for individuals and their families.
What Is the Outlook of This Condition?
There are multiple challenges faced by individuals affected by complete androgen insensitivity, including psychologically coming to terms with the conditions, sexual dysfunctioning, infertility, etc. However, appropriate medical and psychological treatment can lead to improved psychosexual development in women affected by this condition.
Conclusion:
Complete androgen insensitivity is a rare, inherited, and genetic disorder that is characterized by the inability of the body to respond to androgens. Individuals affected by this condition are genetically male but have the physical attributes of a female. However, the genitalia is underdeveloped. The main symptom of this condition that is also used in the diagnosis is the absence of menses even after attaining the age of puberty. Currently, only symptomatic treatment of the condition is available.
