Mathis, who led the NFL with 19-1/2 sacks last season, has been suspended by the league for four games to open the season after Commissioner Roger Goodell said in a statement that it isn't his job "to override the policy's procedures and assess discipline on an after-the-fact, ad hoc basis."
The NFL's statement said that the unnamed drug Mathis was prescribed is not acknowledged by the Food and Drug Administration to help with male fertility.
"The drug for which Mr. Mathis tested positive is not approved by the FDA for fertility in males and is a performance-enhancing drug that has been prohibited for years," the NFL's statement said.
"Importantly, Mr. Mathis did not consult with the policy's independent administrator, a physician jointly approved by the NFL and NFL Players Assn. Nor did he consult with his team doctor, the team's training staff, the NFLPA, the league office or the hotline established under the policy to give confidential information to players. Each of these sources would have warned against using this substance."
Mathis. who said he and his wife are expecting a child, asked fans and teammates for forgiveness and understanding.
“I am deeply saddened that this situation will prevent me from contributing to my team for four games, and I regret that I didn't cross check what my doctor told me before I took the medication, “ Mathis said. “I hope that my fans will understand the unique circumstances involved here and continue to know that I am a man of integrity who would never intentionally circumvent the performance-enhancing substance policy agreed to by the NFL and my union.
“We are thrilled that we will be welcoming a new member in several months, but I apologize to my teammates, coaches and Colts fans that I will not be able to contribute to my team for the first four weeks of the 2014 season. I will work extremely hard during that time to stay in top football shape and will be prepared to contribute immediately upon my return.”
Mathis became the Colt's career sacks leader last season with 111 in 11 seasons.
The Colts issued a statement of support for Mathis that read in part, "We ... wish to assure Robert and our fans that he remains an honored and cherished member of the Colts family and that we support him as he deals with this difficult challenge."