madman
Super Moderator
why would you take AI if your e2 is not way too high? once your e2 gets high if you indeed want to lower it for whatever reason you take a small dose AI to prevent it test from aromatising on next couple of days.. thats true it doesnt affect e2 that was already there but if you take too much it can crash on you since after AI if the dose isnt very small you will not generate any estrogen.. thats how crash occurs
i totally belive when somebody says .25mg crashed them some are very sensitive to anastrozole.. some need like 0.5mg twice weekly to keep their e2 in range while others crash from small .25mg. Vince Carter if .25 wouldnt crash you doesnt mean it wouldnt crash other guys
Every time in every post you always speak of one experiencing a crash as if e2 is non existent!
Brief Introduction to the AIs
The enzyme aromatase is found in the endoplasmic reticulum of the estrogen-producing cell and is the key enzyme in estrogen biosynthesis. The enzyme aromatase is able to convert testosterone into estradiol and androstenedione into estrone. Aromatase activity has been demonstrated in gonads, placenta, brain[33], adipose tissue[34,35], muscle [36], hair [37], bone [38], and vascular tissue [39].
AIs are classified as either type 1 (steroidal) or type2 (nonsteroidal). Examples of steroidal AIs are testolactone, formestane, and exemestane, which inhibit aromatase activity by mimicking the substrate androstenedione. They irreversibly inhibit the aromatase enzyme by covalently binding to it; as such they are also known as “suicidal inhibitors.”
Nonsteroidal AIs inhibit enzyme activity by reversibly binding with the heme iron of the enzyme, resulting in competitive inhibition. Examples of nonsteroidal AIs are aminoglutethimide, fadrozole, anastrozol, letrozole, and vorozole (Table 1).
AIs are further classified into generations based on their efficacy. First generation inhibitors (e.g., aminoglutethimide) are relatively weak and nonspecific, whereas third generation AIs (e.g., letrozole and anastrozole) are most potent, most specific, and least toxic. Their pharmacokinetic properties (t1/2 of 48 hours for ansatrozole and letrozole and t1/2 of 27 hours for exemestane) allow for a once-daily dosing schedule. Their selective inhibitory properties negate the need for corticosteroidal or mineralocorticoid supplementation, which is essential for the nonspecific AI aminogluthimide. The second generation AIs are in between with regard to potency, specificity, and toxicity (e.g., formestane and fadrozole). Third generation AIs have been reported to have close to 100% inhibition of the enzyme, but this is not the case in males. In men, third-generation AIs will decrease the mean plasma estradiol/testosterone ratio by 77% [41,42].This can be explained by the higher plasma concentration of testosterone in eugonal adult men compared with women. .Because inhibition of aromatase is dose dependent, aromatase is less suppressed in the testis compared with adipose and muscle, thus explaining the incomplete efficacy of aromatase inhibition in males. The molar ratio of testosterone to AI and testicular aromatase activity is higher compared with adipose and muscle tissue. As mentioned earlier in this article, low estradiol levels are detrimental to bone health and sexual function. Thus, this incomplete suppression may be advantageous to men,and this lowers the risk of the potential side effects of AIs. Long-term use of potent AIs reduces circulating estradiol levels by 88% [43]. This is associated with adverse effects on bone [44,45] and could possibly be associated with increased body fat in men [22].