These new rules will affect South Africa's double-Olympic champion, with the IAAF putting testosterone quotas on events from 400m to the mile - which include Semenya's preferred 800m and 1500m distances.
Female track athletes with elevated levels of testosterone, a condition known as hyperandrogenism, will be required to lower the amount of the hormone circulating in their blood for six months before being allowed to compete from the quarter-mile to the mile in major worldwide events like the Olympics and the world championships.
"We want athletes to be incentivised to make the huge commitment and sacrifice required to excel in the sport".
Xasa said that the ministry will engage with the relevant bodies and use all avenues to assist Semenya and any other athlete who may be affected "are allowed to participate unhindered by measures to reduce their competitive edge".
It will also sidestep the Court for Arbitration of Sport's (CAS) 2015 decision to suspend regulations on hyperandrogenism in women's athletics.
It has also seen backlash spread across social media, with users calling the regulation "sexist".
It said the new rules would apply to any distance from 400m to the mile‚ meaning Semenya could switch to the 5 000m and 10 000m if she refuses to take medication, which can be used on a daily basis in tablet form.
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'As the International Federation for our sport, we have a responsibility to ensure a level playing field for athletes.
Athletes that choose not to reduce their testosterone levels will only be able to compete in the restricted events at non-international events, compete in events other than the restricted events at global events or compete against male athletes in the restricted events at worldwide events.
This would come as a big blow to South African athlete and world 800 metres champion, Caster Semanya. Two years earlier, Semenya clocked a 1-minute, 55-second time to win her first world title as a teenager in Berlin.
Coe was speaking after the IAAF Council announced last month that following a review of available evidence it would revise its regulations, with the changes coming into force on November 1.
The South African Olympic body's president said it was "disappointed by the IAAF ruling, and especially given that Caster's name is again being dragged through the publicity mill". The treatment to reduce testosterone levels is a hormone supplement similar to the contraceptive pill taken by millions of women around the world.
Athletes, athlete support personnel and National Federation officials with questions about the application of the new Regulations or requiring advice or support is able to contact the IAAF Medical Manager.
Those who want to compete are not required to undergo surgery.