It’s not a problem, sadly it’s intended and no way to get around it.
GS checks the OOC queue on startup and when you make edits to a macro. When combat takes place, Blizzards anti bot code won’t allow changes to take place until combat ends, this happens on many addons and even on Blizzards internal macro system. Updates don’t take effect until combat ends.
Why would you even need to reload your UI through combat?
As Cymiric said its intended. This is not entirely true. Its not intended its just one of the things we have no control over. You can’t modify a button or a macro in combat. This is a Blizzard limitation to prevent active bots from mods or a macro giving you the perfect rotation. GSE then has to wait till you are out of combat before it can setup.