Aromatase inhibitors toxicity

Pandya N, Morris GJ (2006) Toxicity of Aromatase Inhibitors. Semin Oncol 33 688-695... 

Short- to medium-term exposure has shown neurotoxicity, developmental toxicity, immunotoxicity, and endocrine disruption to be relevant end-points. Table 24 summarizes the critical studies for each compound and identifies NOAELs or LOAELs. The degree of each of the toxic end-points differs across the group as a whole. For example, tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

AG), a first-generation type 2 aromatase inhibitor (At), was originally developed as an anticonvulsant but was subsequently found to inhibit the synthesis of adrenocortical steroids. AG is a nonspecific, weak At, administered as a 250-mg dose four times daily with hydrocortisone supplementation because of unwanted adrenal suppression. Because of significant toxicities related to its anticonvulsant structure and its relatively weak inhibition of aromatase, its use has declined considerably with the advent of newer AIs. 

E. Aromatase Inhibitors Anastrozole and letrozole inhibit aromatase, the enzyme that catalyzes the conversion of androstenedione (an androgenic precursor) to estrone (an estrogenic hormone). Both drugs are used in advanced breast cancer. Toxicity includes nausea, diarrhea, hot flushes, bone and back pain, dyspnea, and peripheral edema. 

Mortimer JE (2010) Managing the toxicities of the aromatase inhibitors. Curr Opin Obstetr Gynecol 22 56-60... 

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