Some female runners with naturally high testosterone levels will have to race against men or change events unless they take medication, under new rules issued by athletics' governing body.
The rules, which start on 1 November 2018, would apply to women who race in track events from 400m up to the mile.
The IAAF believes the new measures will stop women with high testosterone levels gaining a competitive advantage.
Olympic 800m champion Caster Semenya is expected to be among those affected.
The South African runner has previously been asked to undertake gender testing by athletics chiefs but no results have ever officially been made public.
Similar restrictions brought in by athletics' world governing body, the International Association of Athletics Federations, were suspended following a legal challenge by the Indian sprinter Dutee Chand in 2015.
"The revised rules are not about cheating - they are about levelling the playing field to ensure fair and meaningful competition," IAAF president Lord Coe said.
"We want athletes to be incentivised to make the huge commitment and sacrifice required to excel in the sport."
Speaking after winning the 800m and 1500m title at the Commonwealth Games in April, Semenya said she could move up to longer-distance events.
"When I do my long runs I feel like I can feed into distance running," the 27-year-old said.
Athletics South Africa said they will support "all our athletes who may be affected by this new ruling".
The rules for athletes who have 'differences of sexual development' apply to the 400m, 400m hurdles, 800m, 1500m, one mile races and combined events over the same distances.
However, 100m, 200m and 100m hurdles are exempt, as are races over one mile and field events.
Female athletes who want to compete must take medication for six months before they can compete, and then maintain a lower testosterone level.
If a female athlete does not want to take medication, then they can compete in:
- International competitions in any discipline other than track events between 400m and a mile
- Any competition that is not an international competition
- The male classification at any competition, at any level, in any discipline
- Any intersex, or similar, classification
Those who want to compete are not required to undergo surgery.
- BBC