My wife has a Ruger LCR in 22lr. 8 shots. I am content with her using it. She grew up hunting and is not "afraid" of a larger caliber. She just does not shoot or train much (I hope that changes, but mother of 3, full time job and just doesn't like shooting) and that is what she is comfortable with. A 8 shot 22 is a better option if that is what she can shoot better.
If a 280 lb man on drugs is after her, the most important factor is going to be her composure.
Find out just how tall I am
By jumping in the middle of a river