Complete androgen resistance is what physicians refer to as a mutation that produces female phenotypes from male carotypes. Patients have a blind vagina and their testes are affected by testicular dystopias. The testes are removed before age 20 to reduce the risk of degeneration.
What is complete androgen resistance?
Complete androgen resistance is also called Goldberg-Maxwell-Morris syndrome and is a form of intersexuality caused by a peripheral hormone receptor disorder. The receptor defect is genetic and corresponds to complete androgen receptor resistance. Testosterone thus has no effect on the body. This phenomenon manifests itself in an absolutely female figure, although the genetic carotype corresponds to that of a man. Patients have a blind-ending vagina and their testes are usually affected by testicular dystopia. The social sex of affected individuals is female in virtually all cases. About one in 20 000 people is born with complete androgen resistance.
Causes
In complete androgen resistance, a defect is localized on the long arm of the respective X chromosome (Xq11). This defect corresponds to a mutation of the gene coding for androgen receptors. In most cases, the mutation corresponds to a point mutation that alters the amino acid sequence. This changes the molecular structure of the androgen receptors so that hormone binding is no longer possible. Because of the lack of testosterone binding, a pseudo-female phenotype develops. In some patients, instead of a point mutation, it is also a mosaic mutation, so that the affected person has cell populations with mutated and defect-free androgen receptors at the same time. Currently, environmental toxins such as bisphenol A are being discussed as the cause of the mutation. The defect may be passed in the X-linked recessive mode of inheritance.
Symptoms, complaints, and signs
Most patients of complete androgen resistance are undoubtedly evaluated as girls at birth. Sometimes patients are larger than average at birth. The testes are often located inside the abdomen or in the groin. Thus, there is testicular dystopia, which can be detected by palpation shortly after birth, if necessary. The attached vagina remains shortened and has a blind end. Neither the uterus nor the fallopian tube of the patient develops during life. Otherwise, female development is not disturbed. Breasts do form. However, the underarm and pubic hair is absent, so that the affected persons are often referred to as hairless women. During puberty, menstrual bleeding does not occur in completely androgen-resistant individuals because of the absence of sex organs.
Diagnosis and course of the disease
The diagnosis of complete androgen resistance is often not made before puberty. Usually, it is the absence of menstruation that first arouses suspicion. Sometimes, it is even an unfulfilled desire to have children that first moves those affected to see a doctor. If the diagnosis is made immediately after birth, it is usually because of a bulge in the groin or the labia majora. This protrusion corresponds to undescended testicles and can be detected as such by ultrasound. To confirm the diagnosis, a laboratory creates a karyogram from the patient’s serum. In making the diagnosis, the physician must show sensitivity and, if necessary, provide psychotherapeutic help to the affected person.
Complications
In complete androgen resistance, various complaints occur. As a rule, not only physical but also severe psychological complaints occur. Patients thus feel very uncomfortable with their bodies and may also feel ashamed of them. It is therefore not uncommon for depression or other psychological upsets to occur. Strong characteristics of a woman appear, which can also lead to mood swings and to inferiority complexes in a man. Likewise, it is not uncommon for the sexual organs to be absent and for puberty to be absent or to have a very delayed onset. The patient’s quality of life is severely limited and reduced by complete androgen resistance. Likewise, the risk of testicular cancer increases enormously, possibly resulting in a reduced life expectancy for the patient.Treatment of complete androgen resistance does not usually lead to any particular complications or discomfort. The testicles can be removed with the help of an operation. Likewise, a vagina can be created so that the affected person can also participate in sexual intercourse. It is not uncommon for patients to require psychological treatment, and parents or relatives may also be affected by this condition.
When should one go to the doctor?
If complete androgen resistance is suspected, the gynecologist or urologist must be consulted. Young women in whom menstruation is absent or delayed at the onset of puberty should seek medical advice. The same applies to young men who develop no testicles or reduced testicles during the growth phase. Complete androgen resistance does not always cause symptoms or complications, which is why medical clarification is not necessary in every case. In most cases, however, physical and psychological complaints arise that need to be treated. A fulfilled sexual life can only be achieved through early and usually protracted therapy. In the best case, the disease is detected before the onset of puberty. Then hormone therapy can be initiated in time and female development can be optimally promoted. Various side effects can occur during treatment, which is why the patient should consult closely with the doctor. The physician must be informed of any unusual symptoms. Regular check-ups by the gynecologist are also necessary after the initial treatment.
Treatment and therapy
Undescended testicles are associated with a risk of degeneration. Affected individuals are usually 32 times more likely to develop malignant testicular cancer than healthy individuals. Therefore, testicular dystopias must be surgically corrected in most cases. Testes in the abdomen in particular, as is most common in androgen-resistant individuals, are 25 percent more likely to degenerate because the ambient temperature at this site favors degeneration. Normally, defectively placed testicles are removed or placed in the correct location during the first years of life. This is not usually the case for completely androgen-resistant individuals. Castration, and with it the removal of the testicles, does not normally occur before puberty in affected individuals. However, removal before the age of 20 is medically recommended. Only if the testicles are preserved as long as possible does puberty not have to be induced artificially. The testosterone formed is converted to estrogen during puberty and female development can occur naturally in this way. Therapeutically, the supportive administration of estrogens is also often used. This ensures a definite development into a female. After the removal of the testicles, the administration of estradiol is often advised, which additionally reduces the risk of osteoporosis and protects the hair as well as the skin and promotes the female appearance. In some people with complete androgen resistance, the shortened vagina must be dilated at some point in life. Only surgical vaginal augmentation makes it possible for some patients to have intercourse painlessly.
Outlook and prognosis
The prognosis for rare, hereditary complete androgen resistance – also known as Goldberg-Maxwell-Morris syndrome – is difficult. Women affected by it essentially have two sexes. But only one is outwardly recognizable. The sexual characteristics of the other sex are concealed. this potentially poses dangers. Male sexual characteristics are therefore often surgically removed at a young age. If this is not done, many medical experts see a poorer prognosis. Testicles or male sex characteristics located inside the body allegedly have a tendency to degenerate due to heating beyond a certain tolerance limit. Whether women with complete androgen resistance feel more masculine because of male sex attributes is not said. Therefore, the prognosis for a happy life as a woman is not necessarily worse. However, the absence of a uterus is very stressful for some women. A desire to have children will not be fulfilled. Some women with complete androgen resistance suffer from hormone therapy with estrogens. However, the administration of testosterone preparations is prohibited. Currently, six medical centers are searching for better hormone therapies and treatment options for complete androgen resistance.The results of this double-blind study should improve the quality of life of those affected. The medical prognosis is good nowadays, but the social prognosis is not. Intersex people continue to feel discriminated against, even though a third gender has now been introduced.
Prevention
Complete androgen resistance cannot be prevented because this disease is a mutation. Prevention is difficult if only because no conclusive research has yet been done to determine which factors are relevant to this mutation. Expectant parents may, however, be able to obtain certainty about the mutation in the fetus during prenatal molecular genetic diagnostics.
Follow-up
In this disease, the measures of a follow-up are very limited. In many cases, they are usually not available to the affected person, so that the disease itself must be treated properly in the first place. Only proper treatment and early diagnosis can prevent further symptoms and complications, so ideally the sufferer should see a doctor at the first signs and symptoms of the disease. Since the disease is usually caused by a tumor, the first priority is to remove it completely. Even after successful removal, the affected person should have regular checkups with a doctor to prevent degeneration and recurrence of the tumors. Likewise, this disease usually requires the use of various medications, paying attention to proper dosage and likewise proper intake. In case of any uncertainties or questions, a doctor should always be consulted first. In this regard, parents must properly monitor the intake of medicines and the progress of treatment, and a doctor should be consulted regularly, especially during puberty.
This is what you can do yourself
Patients with complete androgen resistance may be under constant medical care from an early age, have had one or more gender reassignment surgeries, and/or need to take hormones constantly. All of this requires not only great adherence to therapy, but also psychological stability. The constant feeling of “being different” can wear you down in the long run. Not infrequently, depression and anxiety are the result. Even more than medical care, these patients need psychological support. It is also helpful to join self-help groups and thus make contact with women who share the same fate. Here, for example, the self-help group “XY women” with its respective subgroups “SHG XY women” and “SHG parents XY women” is recommended. The personal stories alone, which are published on the website, can reduce possible threshold fears. The umbrella organization “Intersexuelle Menschen e.V.” also offers so-called peer counseling. This means that “peers advise peers”, i.e. affected persons help other affected persons. This service is free of charge. The members of the association even offer to visit those seeking help at their place of residence and provide advice on the spot. Some women find it helpful to put on makeup or dress in a particularly feminine way so that they no longer have the feeling of being different from others. It is still recommended here to incorporate small feel-good islands into everyday life.
