My wife doesn't like to practice with handgun or any other gun really, but she sure likes shooting unwanted vermin. She is small stature and I got her a youth 20ga. She can go a year without shooting and run outside and shoot a varmint. The learning curve is small with a shotgun that points where you are looking.
I keep it loaded with #4 birdshot and it does the trick on most chicken eating varmints. I figure it will do just fine on anything that need shot inside the house.

The kinda reminds me of Granny Clampit with her shotgun when she gets riled up.

22 handgun with CCI segmented bullets, I've shot animals and" looked" inside.A couple of them inside you and the best Doctor in the world ain't gonna fix you!

I really like the CCI mini mag Segmented bullets , my reservations on personal defense with them is 2 things

rimfire are just not that reliable , while the 150 or so of the segmented mini mags I have shot fine , I have had experiences with rimfire not firing , some times you can turn the round so that the rim gets hit in another spot , they do not seem as reliable as center fire.

the other is penetration , they fragment for sure , but with potentially a lot more mass in the path before hitting vital organs will it be enough.

I had a big racoon in a pasture a few months ago , about a 90 yards out with a 10/22. I shot it several times with the min mags segmenting and it was still moving I knew they were hits , I could hear the thwack of the bullet hitting I lost count of how many times I shot it 8-9 , it was going till it turned at me ,growling and I got a head on headshot that stopped it.

so shot placement is going to be very critical

Absolutely! A Mossberg 500 20 gauge for me #3 buck. Also the top of reciever safety is important, to me it saves a second I may need.

I've killed lions with one shot, found them to be reliable in both her Taurus and my Smith