Androgen insensitivity syndrome

The hormone is made, there is plenty of it in the blood, and the cells still fail to answer. That, in short, is androgen insensitivity syndrome. The chromosomes are XY, the testes have formed and are working, but the receptor protein that picks up the testosterone signal is altered. The message goes nowhere and the body develops along a different path. The condition is present from before birth: it does not develop later in life, and it has nothing to do with anything the mother did or did not do during pregnancy.

Why the cells cannot hear the hormone

The signal is received by the androgen receptor, a protein inside the cell. Its gene sits on the X chromosome. When that gene is altered, the receptor either does not work at all or works at half strength, and testosterone stops shaping what it should: the external genitals in the developing baby, body hair, the deepening of the voice.

The testes themselves form normally. They release testosterone and also a substance that halts the growth of the womb and the tubes. As a result there is no womb and no ovaries, the vagina is short, and the testes have nowhere to descend to, so they stay in the abdomen or in the groin canal.

Complete, partial and mild forms

The more severely the receptor is affected, the more the picture differs.

• Complete. Testosterone has no effect at all. The external genitals look female and the child grows up as a girl. At puberty the breasts develop, because some testosterone is converted into oestrogen, but periods never start and pubic and underarm hair is sparse or absent.
• Partial. The receptor answers halfway and the picture sits in between: the opening of the urethra is not at the tip of the penis, the scrotum may be split, the testes have not descended. Breast tissue often grows at puberty.
• Mild. Outwardly a man with nothing unusual about him; it comes to light by chance, through breast enlargement or during tests for infertility.

When it is picked up

The partial form is usually seen straight after birth: the genitals do not fit the familiar pattern, and there is no hurry to register a sex before the tests are done.

The complete form surfaces in two ways. One is a groin hernia in a small girl: hernias are uncommon in girls at that age, and during the repair the surgeon sometimes finds a testis inside the hernia sac. The other, and the more common, is adolescence: the breasts have grown, height has come, and periods still have not started. No periods by the age of fifteen is reason enough to investigate.

What the tests show

• A chromosome count, which in this syndrome comes back male.
• Blood hormones: testosterone in the male range or above it, and a raised luteinising hormone, because the brain keeps asking for an answer it never gets.
• Ultrasound or magnetic resonance imaging of the pelvis: no womb and no ovaries, with the testes found in the abdomen or the groin canal.
• Testing of the androgen receptor gene, which confirms the diagnosis and explains where the change came from.

How it is passed on and what that means for a family

The altered gene lies on the X chromosome, and in roughly two cases out of three it comes from the mother. She herself is well: her second, ordinary X chromosome makes up for it. In the remaining cases the change arises for the first time, by chance, and the mother does not carry it at all. This is why genetic testing matters: it shows whether sisters and other female relatives should be tested too. The risk is counted afresh for every pregnancy and does not shrink because an earlier child was born without the syndrome. A conversation with a genetics service is best planned before pregnancy rather than after it.

Signs that cannot wait

Most questions here are settled calmly and to a plan, but a few situations are measured in hours.

• A lump in the groin has become hard and painful, will not go back in, and is joined by vomiting and a swollen abdomen. That looks like a strangulated hernia and needs emergency care.
• A firm mass can be felt in the abdomen or groin, it is growing, it drags and aches. Testes left inside the body carry a risk of tumour over the years, and any new lump is checked without delay.
• Sudden groin pain with swelling and redness.
• Oestrogen has been stopped after the testes were removed. This is not a same-day emergency, but it must not be left: without the hormone, bone thins and hot flushes start early.

What helps in living with the diagnosis

There is no treatment that repairs the receptor, so care is built around specific goals. What to do about the testes is decided together with an endocrinologist and a surgeon: they are either kept under surveillance or removed, usually once puberty is over, since until then they supply the body's hormones themselves. After removal, oestrogen is prescribed to protect bone and general wellbeing. A short vagina can most often be lengthened without surgery, using dilators with guidance from a specialist.

The second part, and arguably the main one, is talking. A child is told about their body in stages and in good time, not on the day classmates start discussing periods. Adults are helped by psychological support and by contact with others living with the same diagnosis. Most people with the complete form feel themselves to be women and do not change that in adult life; with the partial form there is more variation, and nobody here disputes a person's right to decide who they are.

Online consultation: what a doctor can do

A video appointment covers everything that does not need an examination. The doctor can explain the chromosome and hormone results when the laboratory report has left more questions than answers. They can say who to see next, whether that is endocrinology, genetics, gynaecology or urology, and in what order, so that time is not wasted going in circles. They can work through hormone therapy: how to take it, what to monitor, what to do about a missed dose. They can prepare you for the conversation with your child and point to where psychological support is found. A strangulated hernia, severe pain and a growing mass in the abdomen cannot be handled remotely; those go straight to a surgeon or to emergency care.

This material is for information only and does not replace medical advice.