On the game that the bug is happening on, I can have stuff that I've never given to anyone at anytime disappear. What you suggested was actually one of my first thoughts as well, but, again, I couldn't replicate the process on a brand new game right away. It always spites me a bit when the game clears out my inventory after getting a Super Cream of Healing, Venus necklace, or some other rare item that I'm trying to save for some specific girl.
Sometimes when I unequip a girl I get back multiple items of the item I'm trying to unequipp. Even stranger yet, last night I saw a Pearl Necklace I unequipped turn into a "Hand mirror" , added separately from the 4 "Hand Mirror" that were already in inventory. Note the difference in capitalization. I sold the abberrant item to the store right away because I was afraid it was going to bug my inventory again, and the item promptly vanished into the ether somewhere. (I've customized my items list to make "A hand mirror" to be "Hand Mirror". I can't begin to imagine where the game pulled that "Hand mirror" description from.)
Maybe it's just my imagination, but it seems I have quite a bit more inventory problems after I've started raiding the catacombs. Whatever is the actual catalyst, once the problem starts it keeps on going.