Hi, I've used estrogel for years I honestly can't say I've noticed any difference when I get to the bottom of the bottle, it really shouldn't make a difference, although I think I may of read it in other posts, the only thing I have noticed which may or may not account for your symptoms feeling worse, is when you do start to get to the bottom of the bottle it seems to give smaller amounts, when I notice that I start a new bottle it may be your not getting the full dose, it does say in the instructions when you notice the pump not returning as quickly when you press, that you should start a new bottle x