The character of Edna Turnblad (a female character who is a VERY large woman with a very "mannish" voice) has always been played by a man in Hairspray, from the original movie, to the stage version, and back to the second movie.
The original Edna was the (in)famous drag star Divine. Harvey Fierstein played her on Broadway, and now Travolta. Actors like the challenge of believably putting across drag roles; see Dustin Hoffman in Tootsie and Robin Williams in Mrs. Doubtfire. (George Wendt [from Cheers] has done the role on Broadway, too. I really have a hard time imagining him as a plausible female.)