I also think there is something significant to be said for keeping an appropriate T:E ratio. I haven't found anything definitive yet that can be used to govern care for all patients, but like almost all aspects of HRT, I have to tailor my treatment regimen to the person. All factors have to be considered, like age, weight, body fat %, activity level, total and free T, and E2. In general, I find that a 15:1 TT:E2 (meaning in TT = 675 in the trough, then E2 should be around 45) ratio seems to be the general area where my patients feel their best. Again this is relative to the patient. Or, when looking at Free T rather than total, I tend to prefer a 1:1.75 or 2 ratio (meaning is cFT = 25 then E2 should be around 43.75 - 50). I have found in the past that pushing the E2 too low, especially using an AI, has the tendency to cause return of malaise and joint aches along with a lowered sense of well being. Again, I cannot back this up with any studies or mass numbers, this is just my experience and what I have seen be successful. Just throwing it out there.