It could be the formatting of the book. The more complicated the code in the book, the longer it takes to turn a page. In this case, "complicated" code generally means bad code. And if the files making up the epub are big, the further through each of the files, the longer it takes to turn a page. And if you have badly coded and long files, it is a lot worse.
My first thought is that closing and reopening a book like this wouldn't affect things. But, there could be a memory leak or something that is only seen after a long session. If there is a memory leak when reading the most likely time for that to happen is each time you turn a page. CLosing and reopening the book could clean this up. Otherwise a restart would be needed.
Lastly, my reading patterns do mean I have a two or three hour session most weeks. And I've had a few four plus sessions with both the Touch and Glo. But, my epubs tend to be clean. I usually end up opening them and changing some of the styles and at the same time clean and simplify the code.