Do trans women have an advantage in sport? The genetics of sex are complex

Last week, the International Olympic Committee announced it will determine whether athletes are eligible for women’s events by mandating a once-in-a-lifetime screening for the male-determining gene, SRY.

But this new rule raises many questions – about why “female” is being defined this way, whether there is evidence trans women have an advantage, and whether a “level playing field” in sport is even possible.

Testing for sex

In humans and other mammals, the SRY gene determines sex in the early embryo. This gene kickstarts the development of testes and their production of androgens – male hormones (testosterone and its derivatives), which drive male development.

The SRY gene lies on the Y chromosome. Males have an X and a Y chromosome, whereas females have two X chromosomes.

Over the decades, sex tests changed from anatomical inspection to using microscopes to detect the second X in women or the Y chromosome in men. But testing was slow, and misdiagnosed athletes with sex chromosome variation.

So a test was developed to detect the SRY gene directly. This is the test the International Olympic Committee will use.

But it’s not as simple to determine “male” or “female” as you might think. The SRY gene activates a network of dozens of genes that promote testis development or block ovary formation. Variation in any of these genes can produce girls with SRY or boys with no SRY.

Indeed, the scientist who co-discovered the SRY gene has warned that this test misdiagnoses athletes with variant sex genes and chromosomes.

For example, some women have an inactive form of the SRY gene that does not induce testis development. Other women have a typical SRY gene, and testes that produce androgens, but have an inactive form of the molecule that activates androgens, so their bodies can’t use male hormones. The SRY test would misdiagnose these women as biological males and ban them.

Likewise, there are men with two X chromosomes who lack SRY but have other variant genes that override it. According to the SRY test they would be allowed to compete in Olympic women’s events.

The International Olympic Committee test must take account of these variants.

What is the evidence for male advantage in sport?

Over decades, physiological studies have shown men have, on average, larger hearts, more efficient lung function and greater muscle mass than women.

As for any trait, there are wide distributions that overlap – for example, there are tall women and short men. However, on average, there can be no doubt men are bigger and stronger than women.

Recent evidence implies that these differences are just the tip of the iceberg. Nearly all our 20,000-odd genes are not on the Y chromosome and are shared by both sexes. But research in 2017 shows that nearly one-third of our 20,000 genes act differently in men and women. Not just in reproductive tissues, but in heart, lungs, brain – everywhere. The same sex differences are seen in monkeys and are apparent before birth.

In three kinds of muscle cells, 2,100 genes work differently in men and women. So sex differences are much more profound than we had appreciated.

Traditionally, these differences have been attributed to the powerful effects of androgens on development at every stage – in the embryo, through childhood and particularly at puberty.

But experiments with mice with genetically manipulated sex chromosomes have showed many fundamental aspects of physiology – such as fat and energy metabolism – are associated not with SRY or hormones, but with the number of X chromosomes.

And the ongoing health advantages provided by the Y chromosome can be seen by the negative effects when men lose it in some cells as they age.

So there are major sex differences in function in every tissue, and it’s not all due to hormones.

But what’s the evidence for transgender advantage in sport?

This is much less clear.

Transitioning from male to female requires hormone replacement. This means suppressing androgens and taking oestrogen, which is much more active in females.

This dramatically changes the body. A trans woman taking oestrogen will develop breasts and more body fat, and lose muscle mass. Her testes will also atrophy.

Trans girls may also take puberty blockers before going through male puberty. These medications stop the body producing the surge of androgens that leads to irreversible physical changes.

So the question of whether trans women athletes have a physical advantage over cis women comes down to understanding what irreversible sex differences took place before and during puberty to organ growth and function, as well as any ongoing non-hormonal differences that might affect function in relevant tissues.

Here the evidence is contradictory, and varies according to when and how someone transitioned. Some studies show significant differences in performance indicators and others don’t. There is some agreement that trans women have, on average, longer limbs, a stronger hand grip and greater muscle mass. But after two years, their cardiac and respiratory function resembles that of cis women.

We have no data on gene activity in trans women athletes, so there are questions we can’t answer. Do the 2,100 genes in their muscle cells revert to a female pattern of activity? Do other genes on the Y chromosome protect their heart and kidney function? Does the lack of a second X improve their fat and energy metabolism?

Where is this level playing field?

So where does this leave the International Olympics Committee ban on transgender athletes? Do we need more data? Do we need to modify our thinking?

I would expect more data would just confirm that trans women who went through male puberty do, on average, have some advantages in organ size and function that are not reversible by hormone therapy or are hormone-independent. Even if transition was before puberty, non-hormone effects apparent in the early embryo probably manifest as more subtle differences in performance.

These differences may be slight. But cis women may contend they are significant in elite sports, where competitors can win medals by running or swimming 0.01 seconds faster than everyone else.

Like many attempts to regulate human behaviour, this ban founders on human variability.

Further complicating things, there is already great physical variation among cisgender athletes in the very attributes that make them excel at sport. For instance, variation in androgen levels has already provoked calls to ban hyper-androgenised women and to mandate allowable hormone levels.

This gets a bit ridiculous – do we ban exceptionally tall women from playing basketball?

Participation in sport is important for health and social connections. Sometimes it’s a lifesaver for trans women.

So discussing alternatives – such as open competitions that run alongside the Olympics, or categories based on something other than sex – remains crucial.

But maybe we need to admit that the playing field in sport can never be truly level. Elite athletes are probably off the charts in many physical and physiological attributes. Is this fair on the rest of us?