As drugs go, it is incredibly safe if used correctly. After your initial loading dose for one to two weeks, the systemic absorption is so, so small. But you must be consistent to build up a layer of cells on the vaginal wall, a process called cornification. This wall limits absorption so you must be consistent in using Vagifem or any other topical estrogen product for the peri/vaginal area. There are great studies on this in US and most likely UK.
