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She said the former cyclist was forthcoming in what she described as an exhausting and intense interview taped Monday in Armstrong's hometown of Austin, Texas.
"We were mesmerized and riveted by some of his answers," she told CBS.
While the interview was revealing, Winfrey said, his demeanor surprised her. "He did not come clean in the manner that I expected," she said without elaborating.
Asked whether she thought it was difficult for him to "come clean" to her, Winfrey responded, "Yes. I think the entire interview was difficult."
It was not immediately clear why Armstrong apparently chose to acknowledge doping after years of denials.
Juliet Macur, the New York Times reporter who broke the news on January 4 that Armstrong was considering an admission of doping, said the athlete is too driven to accept life without sports.
"He has had (several months) to think about how he is lonely, how he doesn't have the adulation of fans at the finish line and nobody to beat right now," she said. "And it's driving him nuts."
Armstrong has been seeking to participate in triathlons sanctioned by U.S. Olympic authorities. Armstrong excelled at triathlons as a teenager and went back to the sport after retiring from cycling. He has been banned from officially sanctioned events.
Paul Willerton, who raced with Armstrong in the early 1990s, said any confession would be "just a starting point" for the cycling star.
"There are a lot of people still lying," Willerton said, naming former Armstrong consultant Dr. Michele Ferrari, and Johan Bruyneel, the onetime director of Armstrong's U.S. Postal Service team. "These guys are still perpetrating the lies and deception that Lance ruled over, and Lance holds the keys. He wants his control back, and he desperately wants to be liked by the American public. And you can't have it all."

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