October 17, 2011 12:00 PM

Rosie O’Donnell glances around at the bare walls in her dressing room at Chicago’s Harpo Studios and sighs. “They took down all the photos of Oprah with everyone,” says the comedian, who is grabbing a bite in between test runs of her new talk show, The Rosie Show, which is taping at The Oprah Winfrey Show‘s former home. “I would have liked to have them here, but she said it’s my studio now.” And in making it her own, O’Donnell has turned the thermostat down (“I’m in menopause; I’m worried about hot flashes!”) and the laughter up. “Being on the show has improved my life. Like, they took me to get all new bras! For a decade I haven’t been wearing one. Now I’m bringing sexy back,” she says, pulling her blouse to the side to reveal a red lacy number. “It’s a whole new me.”

Nearly a decade after ending The Rosie O’Donnell Show, the comedian once touted as the Queen of Nice-but who later became known for her public feuds with Donald Trump and View cohost Elisabeth Hasselbeck-is returning to her “cutie-patootie” roots with her nightly talk show, which premieres Oct. 10 on Winfrey’s network OWN. Yet stepping back into the spotlight after an ill-fated 2006-07 run on The View and a low-key 18-month gig hosting Sirius XM’s Rosie Radio took a little coaxing. “I was terrified. I didn’t know anyone,” says O’Donnell, 49, of moving to Chicago for the show. But ultimately, the decision was easy. When starting her first talk show, “I was 33, I had one child. Now I’m about to be 50, I have four kids [she shares custody of Parker, 16, Chelsea, 14, Blake, 11, and Vivienne, 8, with ex-wife Kelli Carpenter], I came out…. It’s a whole different thing. I’m so much more relaxed in my own skin.”

Crediting hormone replacement therapy for helping keep her anger in check, O’Donnell says her life is more manageable now on all levels. “I started on the hormone cream right after The View,” she says, adding that she began showing signs of “the ‘pause” at 41. “Hormones helped my sleeping; it helped my energy level, it helped my sex drive immensely,” she says. “When you are in menopause, you have no sex drive at all. Tom Cruise and Angelina Jolie could come into the bedroom and you’d be like, ‘Do you want to watch Dance Moms? There’s a marathon on Lifetime.'”

The mood boost is good news for O’Donnell’s new girlfriend, Michelle Rounds, whom she met a few months ago during a Starbucks run. “I didn’t think she was gay,” O’Donnell recalls. “She was holding this little puppy, and I thought, ‘There’s a cute girl with a puppy’-and I was looking for a puppy! So we started to talk.” O’Donnell was smitten but wary. “She didn’t look like any lesbian I’ve ever met.” She and Rounds, 40, have been together ever since. Says O’Donnell: “It’s very exciting and fun.”

It also helped heal the wounds from her breakup with Carpenter. (They separated in 2007 and split for good two years later.) “It was very hard to be divorced,” says O’Donnell, whose subsequent relationship with painter Tracy Kachtick-Anders ended last January. “I didn’t have any idea how to date. I’m not good at it. I’m the stereotype for monogamy.” In addition to her new romance, O’Donnell is adjusting to a life spent partly away from her children. “I have the kids half the time, and Kelli is really flexible,” she says. “We work well together in terms of parenting them.”

Motherhood has always been a priority for the comedian, who walked away from her first talk show in 2002 so she could spend more quality time with her family. “I think I’m a great mom, which is really arrogant, but I do,” she says. “It’s the best thing I ever did. They saved me; they’re the life preservers that keep me afloat.” While Chelsea has moved with her mom to the Windy City, Parker is enrolled in military school. “I did not send him; he really wanted to go. And he loves it, which makes me really unhappy,” she admits. “We have a code word. I’m like, ‘If you ever say “pineapple,” I will come get you.’ I send a postcard and I put ‘Pineapple?’ But no, he loves it.”

O’Donnell hopes her fans feel the same way about her new talk show, and credits Winfrey for wooing her out of semi-retirement. The comedian turned down lucrative offers for another syndicated show to instead appear on Winfrey’s fledgling, and struggling, OWN network, which averages 247,000 viewers in prime time. “But it wasn’t about the money,” she says. “Oprah made me believe I could do it again.” And O’Donnell-who meditates in her bedroom each morning and night-insists she is ready to face any critics with a smile. “I don’t Google myself,” she says. “You know what your truth is, and you have to live in there.” Pals say she’s been doing exactly that. “There’s a certain buoyancy to Rosie now,” says actress Natasha Lyonne. “There’s a lot of excitement there.”

On the eve of turning 50, O’Donnell now considers every day a gift. “My mom died [of breast cancer] at 39,” she says, “so I’m on the bonus plan.” The comedian also has big plans for her future, which she hopes includes marriage and more kids. “There’s destiny involved, so I don’t worry about it too much,” she says. “All I can do is be the best I can be.”

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