The term intersex is synonymous with differences/disorders of sexual development (DSD). We are taught in grade school that men have XY chromosomes and have a penis and testicles. Women are XX and have a vagina and uterus. And some go so far as to claim that those two sexes are the only human sexes. Well, they’re wrong. People with DSDs or who are intersex are those whose biological sex is different in some way.
Obviously, human embryology is complicated. But here’s a simplified summary. As embryos we’re all the same. Our gonads are the same blobs of tissue. The genital tubercle, a lump of tissue with a fancy name, can become either a penis or a clitoris. With testosterone and working testosterone receptors, the tubercle grows and becomes a penis. Likewise, the gonads become testicles. Without testosterone and working receptors, those structures become a clitoris and ovaries.
What are intersex medical conditions?
Here are two examples of intersex/DSD medical conditions.
An individual can have XY chromosomes, have testosterone, but have testosterone receptors that don’t work. Without working receptors, their body develops along the “female” path. They have a vulva, vagina, and clitoris. They also have testicles inside. This is called Androgen Insensitivity Syndrome (AIS).
AIS can be “complete”, where the receptors don’t work at all. Or it can be “incomplete” where the receptors work a little, and the person has a more mixed biological picture. Individuals with AIS often present and think of themselves as female. They may not even know they have AIS until they don’t have periods or try to get pregnant.
On the other hand, an individual can have XX chromosomes and have hyper-active adrenal glands. The adrenal glands sit on top of the kidneys and produce a lot of different hormones. That includes some sex hormones. So hyperactive adrenal glands means more testosterone. More testosterone means that genital tubercle becomes a penis and the labia become a scrotum. So the individual has a penis and scrotum, but has ovaries hidden inside. This is called Congenital Adrenal Hyperplasia (CAH).
Like AIS, CAH can be more “complete” with a fully developed penis and scrotum. CAH can also be “incomplete” with a mixed picture. Individuals with CAH often identify as female. Some do identify as male. Some forms of CAH are potentially fatal, since the adrenals also make hormones that change how salt is handled by the body. Individuals with that form of CAH, called “salt wasting”, need to take steroids lifelong. Today, we test infants for CAH at birth.
Other forms of intersex exist. However those are the two discussed in the paper. If you’re not familiar or comfortable with intersex terminology, it’s probably a fair place to start.
So what about this week’s paper?
This week is a paper published by Beale et al. They examined long term health outcomes in intersex individuals. Their paper summarizes the published research.
We don’t have a lot of data on long term health outcomes in intersex individuals. Physicians used to advocate for early surgery for infants and a gender assignment. Physicians feared that children would be confused if they knew they were intersex. So they recommended that the person not be told they were intersex. Then intersex adults spoke up.
Surgery for infants is no longer standard. Effective treatment of intersex children really only started in the 1960’s. It didn’t become patient-centered until much later. So we don’t have many older intersex people to study or listen to. But we are starting to collect data. Let’s look at what we have.
Congenital Adrenal Hyperplasia
People with CAH need to be on steroids life-long. The steroids keep the adrenal glands quiet. Without steroids, the adrenals go back to producing lots of testosterone. The person may become masculinized. And for some patients, the adrenals may produce too much of the hormones that balance salts and water. That is life-threatening. Consistent visits with a health care provider throughout their lifetime is important.
But we also know that steroids have their risks. Osteoporosis is one risk. So far, individuals with CAH do not appear to be at higher risk for osteoporosis. The other known risks for people with CAH are obesity, high blood pressure, and abnormal lipids (including high cholesterol). So far we don’t yet know if there’s a clinical impact yet. That is, we don’t know if people with CAH are at higher risk for heart attacks or strokes. Studies will continue to follow people with CAH to find out.
Individuals with CAH are able to get pregnant as long as they have a uterus. They do need higher doses of steroids during their pregnancy. Additionally, they may need psychological support through their lifetime. But their quality of life is similar to that of people with other adrenal conditions.
Androgen Insensitivity Syndrome
AIS does not have a long term need for medications like CAH does. However, there are risks associated with having testicles inside the human abdomen. Testicles like to be kept cool. That’s why they migrate to the scrotum. Individuals with AIS are infertile because of the warmth of the abdomen. And testicles that stay in the abdomen have a risk of developing cancer. For that reason, we advise people with AIS to have their gonads surgically removed.
Some people with AIS may choose to keep their gonads until they go through puberty. The testosterone that’s produced by the testicles gets converted to estrogen in their bodies. So they can have puberty without taking hormones. Keeping the gonads that long is a risk, though. People with AIS need to talk with a knowledgeable physician about gonad removal.
For people with AIS who have had their gonads removed, starting hormone replacement therapy is crucial. Sex hormones are needed for healthy bones. If they have a uterus they should receive both estrogen and progesterone. The progesterone protects the uterus from developing cancer. If they don’t have a uterus, they can take just estrogen. Remember – their testosterone receptors don’t work, so giving testosterone won’t help. Individuals with AIS can become pregnant through egg/sperm donation if they have a uterus. Otherwise they will need to adopt or use a surrogate.
Just as with CAH, psychological support for people with AIS may be crucial. AIS can also be diagnosed later in life than CAH, so making sure the patient knows their diagnosis and is supported during that time is important.
As with LGBT health, we just don’t know a lot about the long term health of people with intersex conditions. Long term risks of cancers like breast cancer, cardiovascular disease, and other diseases/disorders are unknown. Stay tuned, and I’ll continue to cover studies as they’re published.
What can you do with this information?
First — if you are an intersex individual or have been diagnosed with a DSD, I recommend joining a study. We need data. Second — find a doctor who treats you well. Keep them in the loop. See them regularly. Ask them questions. If you need to change doctors, make sure you have all your records. Third — take care of yourself. Eat well. Exercise Take your medications. Avoid or reduce drug use. And remember to breathe and enjoy life.
Want to read the study for yourself? The abstract is publicly available.