Been taking activella for at least at 5 or 6 yrs. Took Premarin at low dose before that. Decrease dose 2yrs. ago from 1.0 to .5 A little adjustment took a few months. Ok know, but still have terrible hot flashes ea. time I've tried to come off. I'm 58 & will wait a few more yrs. before try to come off again. I've had no problems with Activella.