Law professor Steve Cornelius was appointed to the International Association of Athletics Federations tribunal late last year.
He said in his resignation letter that he could not in good conscience continue to associate himself with "an organisation that insists on ostracising certain individuals, all of them female, for no reason other than being what they were born to be."
He added: “On deep moral grounds I cannot see myself being part of a system in which I may well be called upon to apply regulations which I deem to be fundamentally flawed and most likely unlawful in various jurisdictions across the globe."
The letter was published on Twitter on Tuesday by sports lawyer Gregory Ioannidis, who described himself as a colleague of Cornelius.
Reuters has contacted the IAAF, athletics' global governing body, to request comment on the resignation.
The new hyperandrogenism rule, which was announced by the governing IAAF last week, has put the spotlight back on South African Caster Semenya, whose long reign as the queen of middle distance running looks set to be ended.
Cornelius' letter of resignation, which was addressed to IAAF president Sebastian Coe, follows Monday’s call by Canada's athletics federation for a rigorous review of the new rules on hyperandrogenism.
The new regulations lay down a series of criteria for athletes with a Difference of Sexual Development (DSD) to be eligible to compete internationally in certain events.
The rules would effectively force South African double Olympic champion Semenya to lower her levels of testosterone in order to compete.
The 27-year-old has faced years of complaints that her hyperandrogenism gave her an unfair competitive advantage.
The condition is characterised by higher than usual levels of testosterone, a hormone that increases muscle mass, strength and haemoglobin, which affects endurance.
South Africa’s sports minister Tokozile Xasa has said she is seeking to take up the matter with the IAAF and the country’s ruling party, the African National Congress, called the policy "blatantly racist" last week.
The new rule comes into effect in November unless overturned by the Court of Arbitration for Sport (CAS).
Athletics authorities have struggled to find a solution to the issue that respected the rights of Semenya while also providing what they say is a "level playing field".
(Reporting by Mark Gleeson in Cape Town; Additional reporting by Gene Cherry in in Raleigh, North Carolina; Editing by Toby Davis)
