Biological sex is all over the news lately.
Between the presidential executive order affecting passport policy, moving transgender inmates between prisons and regulating women's sports, appeals to "the biological reality of sex" are constant.
The truth is that biological sex, like a lot of scientific categories, is nuanced.
It's defined by multiple criteria – including chromosomal, chemical, and physical factors – that can, and do, change over a person's lifetime. And it's a reality that's definitely not limited to male and female.
Even the way medical professionals predict biological sex has changed over time.
Doctors used to determine fetal sex with an ultrasound during the second trimester; nowadays, tests are done with a blood test as early as the end of the first trimester. When a person is pregnant, the placenta sheds DNA into the bloodstream. Labs can take samples of that blood, sort out that fetal fraction and analyze it to look at the chromosomes.
How is sex determined using chromosomes?
You might remember learning in high school biology that all the genetic information in the human body is packaged into 23 pairs of chromosomes. The first 22 pairs tend to look similar in all humans, and the last one is usually either an XX pair (assigned female) or an XY pair (assigned male).
But there are more possible chromosomal variations than just those two, including XXY, XYY and XXX. Plus, the Y chromosome isn't the only determining factor for genetic sex. Researchers have found sex-influencing genes present in the other 22 pairs of chromosomes.
How is sex determined using chemicals?
Another big part of sex and how it develops has to do with chemical hormones such as androgens, estrogen and progesterone. All humans have these hormones – just in differing quantities and cycles – and pediatric endocrinologist Faisal Ahmed says they fluctuate throughout our lives.
A fetus gets the first hit of these hormones in the womb, which triggers things like genital growth and certain types of brain development. Within the first six months of birth, babies have another hormonal surge that endocrinologists call "mini-puberty." And then there's the iconic increase in hormones, which causes adolescent puberty.
Each of these hormone surges triggers the development of other physical characteristics, some of which medical professionals use to determine sex.
"Certainly you would see that there are some hormones which are more likely to be present in a man, and there are some hormones which are more likely to be present in a woman," Ahmed says. "But there are several scenarios where a boy may not necessarily make the male hormones for whatever reason, or there is a girl who makes possibly the male hormones."
How are physical characteristics used to determine sex?
Medical experts often determine sex by observing internal genitalia like ovaries or external genitalia like penises and testes. They also also look at secondary sexual characteristics. These don't usually develop until puberty and include traits like breasts or facial hair. A person's voice, height, fat distribution and muscle mass are other hormone-influenced characteristics that are often used to determine sex.
But these traits don't always fall on a strict binary.
There are tall women and short men, women with flatter chests and men without facial hair; people's appearances can vary widely.
Why not define human sex by reproductive capacity?
This is, in part, what President Trump's recent executive order suggests: two distinct sexes — one that produces large reproductive cells (i.e. eggs) and one that produces small reproductive cells (i.e. sperm). The issue is that all humans' reproductive capacity changes throughout their lifespan – children and menopausal adults, for example, cannot reproduce, but that doesn't mean their biological sex is invalid. Plus, there are rare cases of people born with both ovarian and testicular tissue.
In short, science has documented humans who produce viable eggs, sperm, both, or neither. There's a wide range of possibilities!
What if these common determinants of sex don't align?
All these criteria for determining sex have the potential to differ from one another or to be ambiguous. Someone's chromosomes might be XY, but that person doesn't have a penis; or someone can have a penis as well as internal ovaries.
These differences generally fall under the umbrella of something called intersex conditions.
"Intersex is an umbrella term for biological conditions where a child is born with physical characteristics or genetic characteristics that don't fall into our society's neat definitions of what is male or female," says physician and adult urologist Ilene Wong.
How common are intersex conditions?
A lot more common than you might think!
Ahmed specializes in treating these conditions in children. He says that differences in sex development, specifically ambiguous genitalia, tend to affect 1 in every 2500 people. But Wong says that if you include other common factors like adrenal insufficiency and the chromosomal variations discussed above, intersex conditions are more common than that estimate.
The most commonly cited statistic is that intersex conditions overall affect 1-2 in every 100 people. That would make being intersex about as common as having red hair – and more common than being an identical twin.
Despite its prevalence, Wong says that in the past, there was a big push to "normalize" intersex patients' bodies. Doctors would operate on intersex patients, usually without those patients' full understanding or consent, so their bodies would conform to more typical sex assignments.
In 2018, the American Academy of Family Physicians issued a statement opposing medically unnecessary surgeries on intersex children and recognizing the medical trauma that this kind of surgery had caused.
But Wong says there's still a huge information gap when it comes to intersex bodies and medical treatment. That's why for her, spreading public awareness of intersex conditions – and connecting her intersex patients to advocacy resources and peer support groups – is so important.
"For so many doctors, we're paid to know what to do, we're given a status in society for having information. But with intersex [patients], you just have to have humility and know what you don't know," Wong says. "And there's a lot that we don't know."
Want the episode to cover more nuances of human biology? Let us know by emailing shortwave@npr.org! We're also always open to other story ideas you have.
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This episode was produced by Berly McCoy and edited by Rebecca Ramirez. Tyler Jones checked the facts. Kwesi Lee was the audio engineer.
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