Since I wear a size 9 glove, my opinion about what will best fit your lady's small hands isn't worth spit, so I'll keep it to myself.
However, my mother was a small woman, who wore a size 3.5 ring. She stood 4' 10.5" and never weighed over 108lbs. She was, however a very determined woman. Dad once got her an Ortgies .25acp. While the grip was acceptable, she lacked the strength in her hands to rack the slide to load/unload the gun (small fingers and a very small gripping area + strong spring meant problems for her).
She could shoot a 1911, and actually rack the slide, but it wan't easy for her. She could shoot Dad's S&W M28 6" .357Magnum, with the factory stock "magna" grips (the small ones), but the weight of the large revolver was a chore for her.
She was deadly accurate with her Ruger Super Bearcat, and comfortable shooting it. Since its "only" a .22 lots of folks are going to sneer at it for self defense, but when push comes to shove a small gun that you shoot well and are comfortable and confident with is better than a larger one that is difficult to use. Only hits count, and hits with a .22 (or any small caliber) count for more than misses with everything else.
She was also proficient at close range with her father's double barrel 12ga shotgun, fired from the hip. She would just hold on to the gun, and in her words "let it swing" when she shot it.
As to having a gun left ready for her, one that your lady could shoot, but have trouble loading, thats ok (safe storage concerns adequately addressed, of course), BUT Murphy being the devil that he is, there is the risk that the one time its not ready for her use, would be the one time she would need it most.
I once knew a statetrooper, and a big guy at that, who's home defense gun was a Ruger .22 auto (the MK I). He was quite happy with it. Now, this gentleman could, with his back to the target, turn, draw and empty the gun in about a second and a half, cutting the eyes out of a silhouette target at 7 yds. I've seen him do it, more than once. Don't ignore a .22 as an option, if your lady can use it fast and well. Its a lot better than bare hands and a scream.