Aromatase inhibitor

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Aromatase converts testosterone to estradiol
Aromatase converts androstenedione to estrone

Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. They may also be used off-label to reduce increase of estrogen conversion during cycle with external testosterone. They may also be used for chemoprevention in high risk women.

Aromatase is the enzyme that synthesizes estrogen. As breast and ovarian cancers require estrogen to grow, AIs are taken to either block the production of estrogen or block the action of estrogen on receptors.

Types of AIs[edit]

There are 2 types of aromatase inhibitors (AIs) approved to treat breast cancer:[1]

  • Irreversible steroidal inhibitors, such as exemestane (Aromasin), forms a permanent and deactivating bond with the aromatase enzyme.
  • Non-steroidal inhibitors, such as anastrozole (Arimidex) and letrozole (Femara), inhibit the synthesis of estrogen via reversible competition for the aromatase enzyme.

Mechanism of Action[edit]

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue. The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body's estrogen is produced in peripheral tissues (outside the CNS), and also a few CNS sites in various regions within the brain. Estrogen is produced and acts locally in these tissues, but any circulating estrogen, which exerts systemic estrogenic effects in men and women, is the result of estrogen escaping local metabolism and spreading to the circulatory system.[2]


Arimidex (anastrozole) 1 mg tablets

Available aromatase inhibitors (AIs) include:




In addition to pharmaceutical AIs, some natural elements have aromatase inhibiting effects, such as damiana leafs.



In contrast to premenopausal women, in whom most of the estrogen is produced in the ovaries, in postmenopausal women estrogen is mainly produced in peripheral tissues of the body. Because some breast cancers respond to estrogen, lowering estrogen production at the site of the cancer (i.e. the adipose tissue of the breast) with aromatase inhibitors has been proven to be an effective treatment for hormone-sensitive breast cancer in postmenopausal women.[4] Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women. When aromatase inhibitors are used in premenopausal women, the decrease in estrogen activates the hypothalamus and pituitary axis to increase gonadotropin secretion, which in turn stimulates the ovary to increase androgen production. The heightened gonadotropin levels also upregulate the aromatase promoter, increasing aromatase production in the setting of increased androgen substrate. This counteracts the effect of the aromatase inhibitor in premenopausal women since total estrogen is increased. Ongoing areas of clinical research is optimizing adjuvant hormonal therapy in postmenopausal women with breast cancer. Although tamoxifen (SERM) had been the traditional drug treatment of choice, the ATAC trial has shown that clinical results are superior with an AI in postmenopausal women with localized breast cancer that is estrogen receptor positive.[4] Trials of AIs in the adjuvant setting (given to prevent relapse after surgery for breast cancer) show that they are associated with a better disease-free survival than tamoxifen, but no conventionally-analyzed clinical trial has shown that they have an overall survival advantage compared with tamoxifen, and there is no good evidence they are better tolerated.[5]


Bodybuilders who take anabolic steroids may also use AIs, such as anastrozole, to avoid estrogenic effects, such as gynecomastia, via preventing their elevated levels of testosterone from being converted to excess estrogen. Although anastrozole is reported by steroid users to work well in preventing and also reversing minor symptoms of gynecomastia, only the selective estrogen receptor modulator, tamoxifen, has been shown to be more successful at treating pubertal gynecomastia than placebo. These results are not unexpected due to the significant etiological differences in steroid-induced gynecomastia (excess estrogen) and pubertal gynecomastia (hypersensitive tissue). Tamoxifen has been reported to be effective in treating both groups, showing the acute anti-estrogen action of tamoxifen on the affected tissue provides faster relief in the initial stages of treatment, especially as nipple pain or sensitivity is common in the steroid group, often occurring independently of tissue growth.[8][9]

Investigations and research has been undertaken to study the use of aromatase inhibitors to stimulate ovulation, and also to suppress estrogen production.[10] Aromatase inhibitors have been shown to reverse age-related declines in testosterone, including primary hypogonadism.[11] Extracts of certain mushrooms have been shown to inhibit aromatase when evaluated by enzyme assays, with white mushroom having shown the greatest ability to inhibit the enzyme.[7] AIs have also been used experimentally in the treatment of adolescents whose predicted adult height was low.[12]

Side effects[edit]

Side effects include an increased risk for developing osteoporosis and joint disorders such as arthritis, arthrosis and arthralgia. Bisphosphonates are sometimes prescribed to prevent the osteoporosis induced by aromatase inhibitors, but also have another serious side effect, osteonecrosis of the jaw. As statins have a bone strengthening effect,[13] combining a statin with an aromatase inhibitor could help prevent fractures and suspected cardiovascular risks, without potential of causing osteonecrosis of the jaw.[14][15] The more common adverse events associated with the use of aromatase inhibitors include decreased rate of bone maturation and growth, infertility, aggressive behavior, adrenal insufficiency, kidney failure, and liver dysfunction. Patients with liver, kidney or adrenal abnormalities are at a higher risk of developing adverse events.[16]


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  2. ^ Simpson E (2003). "Sources of estrogen and their importance". J. Steroid Biochem. Mol. Biol. 86 (3-5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515. 
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  6. ^ Grube B, Eng E, Kao Y, Kwon A, Chen S (2001). "White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation". J. Nutr. 131 (12): 3288–93. PMID 11739882. 
  7. ^ a b Chen S, Oh S, Phung S, Hur G, Ye J, Kwok S et al. (2006). "Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)". Cancer Res. 66 (24): 12026–34. doi:10.1158/0008-5472.CAN-06-2206. PMID 17178902. 
  8. ^ Derman O, Kanbur N, Kutluk T (2003). "Tamoxifen treatment for pubertal gynecomastia". Int J Adolesc Med Health 15 (4): 359–63. doi:10.1515/IJAMH.2003.15.4.359. PMID 14719418. 
  9. ^ Plourde P, Reiter E, Jou H, Desrochers P, Rubin S, Bercu B et al. (2004). "Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial". J. Clin. Endocrinol. Metab. 89 (9): 4428–33. doi:10.1210/jc.2004-0082. PMID 15356042. 
  10. ^ Attar E, Bulun S (2006). "Aromatase inhibitors: the next generation of therapeutics for endometriosis?". Fertil. Steril. 85 (5): 1307–18. doi:10.1016/j.fertnstert.2005.09.064. PMID 16647373. 
  11. ^ Leder B, Rohrer J, Rubin S, Gallo J, Longcope C (2004). "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels". J. Clin. Endocrinol. Metab. 89 (3): 1174–80. doi:10.1210/jc.2003-031467. PMID 15001605. 
  12. ^ Hero M, Wickman S, Dunkel L (2006). "Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty". Clin. Endocrinol. (Oxf) 64 (5): 510–3. doi:10.1111/j.1365-2265.2006.02499.x. PMID 16649968. 
  13. ^ Rejnmark L, Vestergaard P, Mosekilde L (2006). "Statin but not non-statin lipid-lowering drugs decrease fracture risk: a nation-wide case-control study". Calcif. Tissue Int. 79 (1): 27–36. doi:10.1007/s00223-006-0024-4. PMID 16868664. 
  14. ^ Lehrer S (2007). "Statin use to prevent aromatase inhibitor-induced fracture and cardiovascular complications". Med. Hypotheses 68 (6): 1417. doi:10.1016/j.mehy.2006.11.022. PMID 17196764. 
  15. ^ Ewer M, Glück S (2009). "A woman's heart: the impact of adjuvant endocrine therapy on cardiovascular health". Cancer 115 (9): 1813–26. doi:10.1002/cncr.24219. PMID 19235248. 
  16. ^ "Aromatase Inhibitors in Products Marketed as Dietary Supplements: Recall" (Press release). FDA. September 20, 2010. Retrieved August 9, 2012.