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If they want to compete in certain events at least — a landmark decision with far-reaching ramifications for other women's sports.
In a 2-1 ruling, the Court of Arbitration for Sport upheld proposed rules issued by track's governing body, the IAAF, saying that they are discriminatory but that "such discrimination is a necessary, reasonable and proportionate means" of "preserving the integrity of female athletics."
The IAAF argued that high, naturally occurring levels of testosterone in athletes like Semenya with "intersex" characteristics that don't conform to standard definitions of male and female give them an unfair competitive advantage, and it decreed a maximum level for females.
The court decision could open the way for similar rules in other women's sports where size, speed and power make a difference, such as weightlifting, boxing, swimming, rugby, field hockey and soccer.
Semenya — a 28-year-old South African whose sculpted biceps and super-fast, blow-away-the-competition times have led others to question her accomplishments — declared she will not be deterred.
"I know that the IAAF's regulations have always targeted me specifically," Semenya said in a statement. "For a decade the IAAF has tried to slow me down, but this has actually made me stronger. The decision of the CAS will not hold me back. I will once again rise above and continue to inspire young women and athletes in South Africa and around the world."
The two-time Olympic champion in the 800 meters will have to lower her testosterone levels by such means as birth control pills or prostate cancer drugs if she wants to defend her world title in September in Doha, Qatar. Semenya is expected to race in the 800m on Friday at a track meet in Doha in what will be the last world-class event before the new rules apply.
Testosterone strengthens muscle tone and bone mass. Because of that, it is against the rules for athletes to use testosterone supplements. Some women have what is known as hyperandrogenism, meaning they have natural levels that are unusually high.
The IAAF rules require women to reduce their levels below 5 nanomoles per litre of blood. According to the IAAF, most females, including elite athletes, have levels of testosterone circulating naturally in their bodies of 0.12 to 1.79 nanomoles per litre, while men have levels that can be dozens or even hundreds of times higher — typically 7.7 to 29.4.
Semenya's level is considered private medical information and has not been disclosed.
The South African Sports Confederation and Olympic Committee decried the ruling, saying, "We maintain that the rules are ill-thought and will be a source of distress for the targeted female athletes."
"This decision marks a massive turning point as it now redefines what a female athlete in particular is," said Natalie du Toit, head of the organization's athletes commission, adding: "Knowing Caster and the hard work she has put into her sport, we support all her endeavors, and we are all behind her."
The IAAF went into the case arguing that female runners with high testosterone have an unfair advantage in events from 400m to the mile. However, the court suggested that the IAAF apply the rules only up to the 800m because the evidence was not clear that women with hyperandrogenism have an edge in the 1500m and above.
Under the rule, female athletes whose medical profiles previously showed high testosterone will be subject to blood tests to prove they have complied.
An appeal to Switzerland's Supreme Court is possible. But judges rarely overturn decisions of the world sports court.
Ross Tucker, a sports science consultant who testified on Semenya's behalf and boasts of a PhD in exercise physiology, said the scientific evidence is insufficient to justify the rules. He said that as a result of the court decision, other sports will essentially copy the IAAF's regulations.
"For them, every fear and concern they had that they will be in the spotlight for introducing similar rules will be gone," he said. "Other sports will be super happy because the pressure's off to develop their own regulations."
He said the ruling moves the world of sports closer to developing its own definition of gender, based on hormone levels.
"'Sporting sex has been introduced," he said. "That is where the decision does have far-reaching effects."
John Brewer, a professor of applied sports science at the Buckinghamshire New University in Britain who supports the IAAF rule, said such regulations could end up being adopted not just by individual sports but by team sports such as rugby, soccer and field hockey.
Hormone-blocking drugs can increase the risk of blood clots, thinning bones, fractures and heart problems.
Semenya was legally recognized at birth as female, but her speed and muscular body have led others to cast doubt on the integrity of her track achievements throughout her career. As a teenager in 2009, she won her first world title in Berlin. Hours before the race, the IAAF asked her to undergo a gender verification test.
She is not the only female athlete with high natural levels of testosterone but has become an unwilling face of the issue. Indian sprinter Dutee Chand has been publicly identified as having high testosterone. Two weeks ago, Olympic silver medalist and Semenya rival Francine Niyonsaba of Burundi confirmed she has hyperandrogenism too.
Referring to the rule, Niyonsaba said: "For me, it's about discrimination. It doesn't make sense. I didn't choose to be born like this. What am I? I'm created by God."
At the 2016 Rio Olympics, Semenya and Chand competed, and other athletes implied that other runners, including medalists in the 800 meters, also had elevated levels.
"I think that we need separate events for them and for us," Nataliia Lupu of Ukraine said after running against Semenya. "You can see that it's easy for them."