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7 minutes
Androgen insensitivity syndrome is a genetic disorder in which a person with male chromosomes has female-looking genitalia. Learn more here.
The disorders of sexual differentiation are a group of inherited conditions that condition the inadequate development of sex, either at the chromosomal, gonadal or anatomical level. Androgen insensitivity syndrome (AIS) is one in which a person has 46 XY sex chromosomes and has female-looking genitalia.
The development of these characteristics occurs because the body is not able to respond to the action of male sex hormones (androgens). However, the gonads found in people with androgen insensitivity syndrome are testicles. Because of this, it was previously called male pseudohermaphroditism either testicular feminization.
How is sex determined?
In total, human beings have 46 chromosomes (23 pairs). Within which a single pair corresponds to the sex chromosomes, being XX for women and XY for men.
However, for the genital sex to correspond to the same sex determined by the chromosomes, a series of events must occur. These happen in specific periods of intrauterine life.
The Y chromosome is the one that indicates that an individual is male. On this chromosome are the genes that encode the signals necessary for the testicles to form. In turn, these produce two main substances:
- Testosterone.
- Anti-müllerian hormone.
The action of the first stimulates the differentiation of the structures that will make up the male reproductive system. While the second is responsible for inhibiting the formation of the female internal genitalia, by causing the Müllerian duct to degenerate.
Instead, female sex determination occurs when the Y chromosome is absentin the presence of a second X chromosome. These chromosomes have genes that prevent the formation of the testicles.
In the absence of anti-Müllerian hormone, the Müllerian duct does not disappear and the tubes, uterus, and upper vagina can form. In addition, in the absence of testosterone, the development of the structures corresponding to the male reproductive system is not stimulated.
What causes androgen insensitivity syndrome?
This disorder of sexual differentiation It is caused by an alteration in the androgen receptor. It is nothing more than the molecule to which the male hormone binds. In the absence of such a union, testosterone does not act.
For this reason, the receptor is said to be resistant to the hormone.
The androgen receptor is encoded by genes found on the X chromosome. Therefore, androgen insensitivity syndrome is considered to have maternal transmission. In the same way, it presents a recessive inheritance.
Effects of the SIA
The diversity of effects in this disorder depends on the functionality of the receptor. In milder cases, the receptor retains some ability to interact with androgens.
Due to this variability, androgen insensitivity syndrome has been classified into 3 different clinical forms of presentation:
- Morris syndrome or complete resistance to androgenic action.
- Partial insensitivity to male sex hormones or Reifenstein’s syndrome.
- Mild cases that were called infertile male syndrome.
1. Complete androgen insensitivity syndrome
This is the most frequent presentation. The resistance of the receptor is maximum, so they are completely unable to bind to sex hormones.
This means that a person with a male chromosomal sex (46 XY) does not develop the corresponding genitalia in utero. Although he does have testicles.
The testicles produce testosterone, but this has no effect in the person with complete androgen insensitivity syndrome, so the male genitalia do not conform. Similarly, the testicles also produce anti-Müllerian hormone, causing the precursor duct of the internal female sex organs to involute.
2. Partial androgen insensitivity syndrome
On the other hand, when there is some response from the receptors to the presence of testosterone, Intermediate stages in sexual development occur. This condition is rarer, but easier to detect at birth.
3. Infertile male syndrome
In this underdiagnosed condition, gross genital anomalies are not commonly seen. However, the man grows up and discovers that he cannot have offspring. Association with gynecomastia has been described.
What symptoms does a person with androgen insensitivity syndrome present?
The best described picture corresponds to complete resistance to male hormones. In this clinical form, the main characteristic is the presence of external genitalia with female configuration normal. This determines that the sex assignment at birth is female.
Early diagnosis becomes difficult. However, despite having normal external genitalia, the following abnormalities occur:
- Short vagina, as its upper portion does not develop.
- Absence of internal organs of the female reproductive system, such as the uterus and ovaries.
- Presence of testicles anywhere along the path of descent.
On the other hand, At puberty they become taller than average. showing the female population. They have little and fine hair located in the armpits and pubis. Menstruation is absent, but they do have breast development.
When androgen resistance is partial, the genitalia at birth will show intermediate characteristics. The baby may have a micropenis with hypospadias or clitoromegaly and fusion of the vaginal lips.
Diagnosis
Depending on the degree of androgen resistance, detecting the disorder at birth will be more or less difficult. In general, in cases with complete resistance, the condition goes unrecognized.
On the other hand, when the genitalia show some degree of ambiguity, the case is usually studied. Otherwise, the process is delayed until puberty, when the adolescent does not have menses.
In cases where an inguinal hernia appears, it is usually corrected with surgeryand it is there that the bulge is recognized to be the descended testicle.
Some of the evaluations that are conducted include the following:
- Karyotype to determine that the chromosome component is male (46 XY).
- imaging studies to evidence the absence of ovaries and uterus.
- Measurement of hormonal parameters in the blood.
- genetic studies that determine the precise mutation that affects the receptor.
Differential diagnoses
Androgen insensitivity syndrome It is the third leading cause of primary amenorrhea. (absence of the first menstruation after turning 16 years old), so the alteration may be suspected in these cases. However, other disorders that you can think of include the following:
- Swyer syndrome or gonadal dysgenesis.
- Mayer-Rokitansky-Küster-Hauser syndrome.
Is there any treatment?
After establishing the diagnosis, each case must be individualized. Sex assignment is a controversial issue. and will depend on the degree of resistance to androgens. Psychiatrists, psychologists, urologists, endocrinologists and geneticists must intervene.
When the resistance is complete and the initial assignment is female, the girl grows up in an environment that gives her enough conviction to develop an identity as a woman. In contrast, in partial insensitivity, sex assignment is often more complicated.
On the other hand, in AIS the testicles have a higher risk of malignancy. This risk increases as time goes by. For this reason, it is currently recommended that the testes be removed after reaching puberty.
Likewise, the patient’s sexual satisfaction must be protected and guaranteed, which is why reconstructive surgeries to create the patient’s gender-appropriate genitalia are essential. There is a database with scientific information and support groups for people with disorders of sexual differentiation.
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