I've spoken with three doctors on this subject. Low doses are the only safe route. General opinion is 250iu/ed on HRT and no more than 500iu/ed on cycle. One doc is an Endo, one is an internist that has many bb's that come to him. The last doc is Swale, who is a well known HRT doc. This is a prime example where more is not better and actually worse in the long run. Also higher doses can give E issues. (This I have experienced myself)