Caster Semenya has lost her landmark legal case against the IAAF.
Semenya challenged the IAAF's proposal to restrict testosterone levels in female runners in events between 400m and a mile.
The double Olympic 800m champion claimed the sport’s governing body's regulation was discriminatory.
She challenged the proposal at the Court of Arbitration in Sport in Lausanne, Switzerland but the surprise decision was announced on Wenesday.
The result means she will have to take medication to reduce her testosterone if she wants to keep running on the international stage.
The IAAF have confirmed the new regulations will come into effect on May 8, ahead of the world championships in Qatar later this year.
Who is Caster Semenya? Olympic champion profiled after losing controversial legal case
Semenya, who has a condition called hyperandrogenism which means her testosterone levels are naturally elevated, was asked to take a gender test as an 18-year-old shortly before she won the 800m at the 2009 World Championships.
Semenya broke her silence on the controversial decision by posting the slogan 'Sometimes it's better to react with no reaction' alongside a shrugging emoji.
South African Semenya had previously stated: "I just want to run naturally, the way I was born."
But CAS said in a statement: "By majority, the CAS panel has dismissed the requests for arbitration considering that the claimants were unable to establish that the DSD regulations were 'invalid'.
"The panel found that the DSD regulations are discriminatory, but the majority of the panel found that, on the basis of the evidence submitted by the parties, such discrimination is a necessary, reasonable and proportionate means of achieving the IAAF's aim of preserving the integrity of female athletics in the restricted events."
However, despite the award in favour of the IAAF, CAS said its panel "expressed some serious concerns as to the future practical application" of the DSD regulations.
