muscled guy bicep curlLetrozole is a non-steroidal competitive inhibitor of aromatase. Unlike the steroidal suicide inhibitors letrozole does not reduce levels of aromatase in the body. It is the most potent inhibitor of aromatase and results in 90-100% inhibition of estrogen formation1,2. It takes about 2 to 3 days to reach maximal inhibition, but may take as much as 2 months to reach steady state levels in the body3. Letrozole has also been shown to suppress cortisol and aldosterone levels2. Suppression of cortisol can be a positive thing both on and off-cycle; however, one must realize that there is a significant rebound effect which can result in higher cortisol levels following letrozole therapy. It is well known that the use of an aromatase inhibitor can reduce HDL cholesterol levels and it is suspected that reduction of estrogen through the use of aromatase inhibitors can result in a compensatory mechanism that may increase sensitivity to estrogen4. Though this mechanism has not yet been determined it may be increased aromatase or estrogen receptor expression or something else entirely5. Aromatase inhibitors have gained in popularity in recent years among steroid users because of the mistaken belief that the lower the estrogen the better. As stated earlier in this text, estrogen plays important roles in male physiology and too much suppression can result in side effects.

1. Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM: An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Cancer. Nov 1;95(9):2006-16, 2002

2. Haynes BP, Dowsett M, Miller WR, Dixon JM, Bhatnagar AS: The pharmacology of letrozole. J Steroid Biochem Mol Biol. Oct;87(1):35-45, 2003

3. Buzdar AU: Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors. Clin Cancer Res. Jan;9(1 Pt 2):468S-72S, 2003

4. Chen S, Masri S, Wang X, Phung S, Yuan YC, Wu X. What do we know about the mechanisms of aromatase inhibitor resistance? J Steroid Biochem Mol Biol. 102(1-5):232-40, 2006

5. Miller, WR; O′Neill, J. The importance of local synthesis of estrogen within the breast. Steroids. 50:537–548, 1987

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