You gotta follow the "rent one first" advice here... My wife, who's been shooting pistols since 10 or 12 years old, has shot my USP45 and USP40, but both were uncomfortable for her.
She's got very thin wrists, and the gun twists her strong-side wrist inward and upward, causing discomfort. But she shoots all our 9mm's without any problems. Even the tiny little Kahr MK9, which is her favorite gun of all, is not an issue for her.
Given time, I'm sure she could adjust to the larger calibers, but she likes her 9mm's, so I don't see any reason to push her to a bigger caliber and bring discomfort to a range session.
Yuuuk, Spider crawlin around, I'm outa here!