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Sports science outlook ILLUSTRATION BY JONAS BERGSTRAND JONAS BY ILLUSTRATION n the excitement of leaving for the sex, based on chromosomes. People usually 1985 World University Games in Kobe, have 46 chromosomes arranged in 23 pairs. Japan, Spanish hurdler María José One of these pairs differs depending on the THE Martínez-Patiño forgot to pack her biological sex of the individual: women typi- doctor-issued ‘certificate of femininity’. cally have two X chromosomes, whereas men “You had to prove you were a woman in typically have an X and a Y. Genetic errors, FUTURE Iorder to compete,” she explains. Without it, mutations and interactions between DNA and she had to take a simple biological test. But hormones can, however, cause a panoply of it produced an unexpected result, and so exceptions to this arrangement. Although a she had to take a more thorough test — one person’s chromosomes might indicate one OF SEX that would take months to process. The team sex, their anatomy might suggest otherwise. physician advised her to fake an ankle injury This is known as intersex or differences of sex to silence suspicion around why she was not development (DSDs). IN ELITE running, so she sat in the stands with her foot The chromosome-based test required by bandaged and watched, wondering what the the IOC involved taking cells from inside the test result meant. cheek. In a cell containing two X chromo- SPORT Sport has a long history of policing who somes, one chromosome is inactive and there- counts as a woman. Blanket mandatory ‘sex fore shows up under the microscope as a dark Sex has long been used verification’ testing was put in place at events spot in the nucleus, known as a Barr body. If to divide many sporting in the 1960s (see ‘Policing sex’) — a time when the dark spot was not clearly identifiable, the women’s participation in sport was on the rise result could then be checked by cataloguing competitions in the name of and many were making huge performance the chromosomes present in a cell. fairness, but are the current improvements. Concerns that men might Martínez-Patiño’s chromosome testing be masquerading as women forced people revealed she was 46,XY — chromosomally rules and enforcement competing in women’s events to undergo a male. Further examinations showed that practices fit for purpose? demeaning visual and physical examination although her outward features were typ- by a panel of doctors. ically female she had internal testes. Her In 1968, the International Olympic Commit- cells, however, were unable to process the By Julianna Photopoulos tee (IOC) adopted a different test to determine hormone testosterone in her body that would S12 | Nature | Vol 592 | 1 April 2021 ©2021 Spri nger Nature Li mited. All ri ghts reserved. ©2021 Spri nger Nature Li mited. All ri ghts reserved. otherwise produce typical male anatomy — a successfully challenge a disqualification from condition known as complete androgen insen- athletics on the grounds of sex. As a result, sitivity syndrome. “I was stunned,” she says. World Athletics ended blanket genetic sex Following the results, Martínez-Patiño was testing in 1992, although it still investigates asked by her national federation to withdraw female athletes when competitors, coaches or from sport quietly. But she made a differ- the media raise questions. The IOC continued ent call, choosing instead to compete in the to routinely test for the SRY gene found on the Y Spanish Athletics Championships in 1986. chromosome until 2000. These tests have only She paid the price afterwards, however, when ever been directed at women with non-typical her medical record was leaked to the media. sex characteristics or intersex traits, never at “I lost everything,” she says. She was barred men, says Katrina Karkazis, a bioethicist at Yale from competition and had her university University in New Haven, Connecticut. fellowship, medals and records revoked. She lost her friends, fiancé, privacy and sense Changing regulations of self. “I felt guilty, like I was to blame for a DSDs are rare, but they have been found to genetic or medical matter,” she says. be more common in female athletes than in But even then, she was not ready to give up. women generally. A study1 involving athletes “You see yourself in the mirror every day. You who took part in the 2011 IAAF World Cham- grew up and developed as a woman — that does pionships in Daegu, South Korea, found that not change,” she says. “I was going to show I about 7 in 1,000 female competitors were EFE/PA IMAGES EFE/PA didn’t cheat anyone.” With the support of sev- 46,XY — a prevalence that is around 140 times eral scientists, Martínez-Patiño proved to the higher than in the general population. Hurdler María José Martίnez-Patiño in 1989. medical commission at what was then called Individuals with this genetic make-up can the International Amateur Athletic Federation produce high levels of testosterone. Known as Athletics meant that, to compete in women’s (IAAF) that she did not have any unfair advan- hyperandrogenism, this can also result from events, individuals had to lower their blood tage over other female athletes. In 1988, her other conditions in women, such as polycystic testosterone levels to below 10 nanomoles licence to compete was restored, but it was ovary syndrome and congenital adrenal hyper- per litre by either hormone treatment or sur- too late for her Olympic dream. After failing plasia. Testosterone makes muscles bigger, gery. Martínez-Patiño, who was part of the IOC to qualify for the 1992 Olympics in Barcelona strengthens bones and increases levels of Medical Commission that adopted similar by one-tenth of a second, she retired to focus oxygen-carrying haemoglobin in the blood. rules in 2012, says that although it was not a on sports science. Its synthetic form is used in doping. perfect solution it was an improvement on past Even before chromosome analysis was attempts to ensure fairness in women’s sport. introduced to determine sex in sport, However, the policy did not remain in force geneticists warned that it was unreliable, for long. In 2014, on the eve of the Common- discriminatory and ill-suited for detecting wealth Games in Glasgow, UK, Indian sprinter people who might have an ‘unfair’ advan- Dutee Chand discovered that her blood tage in the women’s category. Reliance on I FELT GUILTY, LIKE I WAS testosterone level was above the 10-nanomole the presence of multiple X chromosomes to threshold. Rather than take the option of hor- signify being female would not, for example, TO BLAME FOR A GENETIC mone therapy or surgery, as other athletes are identify the roughly 0.2% of men born with thought to have done around this time2, she 47,XXY genetics. Similarly, it would not iden- OR MEDICAL MATTER.” instead chose to fight the ruling at the Court tify women with hormonal conditions that can of Arbitration for Sport. In July 2015, the court cause them to have increased muscle, such as found in her favour and gave World Athletics congenital adrenal hyperplasia. The typical testosterone level in women two years to present clearer scientific evidence Over the decades, sports governing bod- ranges from 0.12 to 1.79 nanomoles per litre, that natural testosterone provides an athletic ies’ regulations have evolved in an effort to whereas in adult men it ranges from 7.7 to advantage. The hyperandrogenism rules were ensure that for a person to participate as a 29.4 nanomoles per litre. This difference suspended, allowing Chand and women with women, they must be a “biological female”, manifests after puberty, when men typically DSDs to compete without restriction. says Stéphane Bermon, a sports physician produce considerably more testosterone than and the director of health and science at World do women. “Testosterone is the main driver Controversial evidence Athletics (formerly the IAAF) in Monaco. “The explaining the difference between male and Attempts to use testosterone as a marker female classification in sports is a protected female performances,” says Bermon. In 2011, of whether an individual can compete in a category,” he says. World Athletics’ current World Athletics became the first international women’s event or has an unfair sporting advan- definition of a biological female is largely based sports federation to adopt regulations govern- tage have been the subject of much criticism. on levels of testosterone. But some researchers ing the competition eligibility of women with One objection is that the typical testoster- doubt the validity of using testosterone to seg- hyperandrogenism, stressing that it was not a one ranges for men and women might not be regate athletes. More broadly, the process of form of sex testing. The move was triggered by as distinct as they first appear. A 2014 study3 sorting athletes by their sex has raised difficult controversy around the sex of South African of 693 elite female and male athletes across questions around medical ethics and human middle-distance runner Caster Semenya in 15 sports found significant overlap in testos- rights that are a long way from being answered. 2009, which forced her to withdraw from sport terone levels between the two groups. Around Martínez-Patiño was the first woman to for 11 months. The rules adopted by World 14% of women had levels higher than what is Nature | Vol 592 | 1 April 2021 | S13 ©2021 Spri nger Nature Li mited. All ri ghts reserved. ©2021 Spri nger Nature Li mited. All ri ghts reserved. Sports science outlook considered the typical female range — some even had levels considered high for a man. And around 17% of men had testosterone levels below the typical male range.

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