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Anastrozole is a reversible competitive aromatase inhibitor (AI) with high specificity and affinity1,2. It has a chemical formula of C17H19N5 and a mass of 293.366 g/mol.
Anastrozole, Estrogen and Testosterone
This molecule binds to aromatase, which prevents the conversion of estrogen to testosterone1. These reductions in estrogen are used in medicine and research to reduce the supply of the hormone to its receptors (ERs) on tumor cells3. A recent trial of the effects of anastrozole on murine ER-positive carcinoma cells found the AI significantly reduced cell viability and proliferation at a range of doses3. It may be intuitive therefore to assume a role for anastrozole in the effects of testosterone on its physiological and pathological effects. However, a recent study using male Fisher 344 rats found that anastrozole had little effect on the bone-conserving properties of testosterone. This study randomly allocated orchidectomized rats to dose-regimens of testosterone, anastrozole, trenbolone (a testosterone analog which cannot be converted to estrogen), both anastrozole and trenbolone or placebo4. The 'testosterone'and 'trenbolone' group suppressed the bone loss seen in the placebo group compared to intact animals, but this was not affected positively or negatively in the groups receiving anastrozole4. In addition, anastrozole did not affect the increases in fat mass and decreases in muscle mass seen in the placebo group4.
Anastrozole is an azole, which leads to its classification as a non-steroidal third-generation aromatase inhibitor5. It is electrophilic, which suggests a role in ion channel activation5.
Anastrozole and Pain
Anastrozole has been found to produce the side-effect of pain when used as a treatment or intervention5. This adverse event most often arises in the form of joint or neuropathic (or nerve damage-related) pain5. This azole has demonstrated the ability to induce or increase pain in murine studies5. Anastrozole has been found to target the transient receptor potential ankyrin 1 (TRPA1) channel, which is a mediator of neuropathic pain, chemical irritation and pain related to inflammatory stimuli5,6. Mouse models of genetic TRPA1 deficiency and blockade have shown that anastrozole administration resulted in the calcium response of this channel5. This indicates a role for anastrozole in models and studies of neuropathy, inflammatory pain and irriation in the future.
References:
1. Geisler J. Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole--of clinical importance? British journal of cancer. 2011;104(7):1059-1066.
2. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383(9922):1041-1048.
3. Topcul M, Cetin I, Ozlem Kolusayin Ozar M. The effects of anastrozole on the proliferation of FM3A cells. J BUON. 2013;18(4):874-878.
4. Beck DT, Yarrow JF, Beggs LA, et al. Influence of aromatase inhibition on the bone-protective effects of testosterone. J Bone Miner Res. 2014;29(11):2405-2413.
5. Fusi C, Materazzi S, Benemei S, et al. Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1. Nature Communications. 2014;5:5736.
6. Trevisani M, Siemens J, Materazzi S, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2007;104(33):13519-13524.
