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Aromatase Inhibitors (AI)


Aromatase Inhibitors are drugs which aim to reduce the levels of oestrogen within the body to the lowest possible level. They only work in women who are post-menopausal. The human body naturally produces oestrogen that requires to be converted to active forms to be functional. Drugs that block the formation of oestrogen in this way lower the blood levels of oestrogen to near undetectable levels.

Types of aromatase inhibitors

There are several Aromatase Inhibitors made by various companies and each has a proper name and a trade name.

Anastrozole (Arimidex)
Letrozole (Femara)
Exemestane (Aromosin)

How do aromatase inhibitors function?

Oestrogen’s are made even in post-menopausal women. Breast cancer is known to depend on oestrogen for its development and progression. Oestrogen is predominately made by the ovaries but also in smaller amounts by other organs such as the adrenals. The adrenal glands are small glands situation above the kidney on each side and produce a hormone called androstenedione which is subsequently converted to oestrogen. The aromatase inhibitors block the conversion of these precursors into active forms of oestrogen. This happens in fatty layers of the skin, the breast and also in the muscles. The enzyme is called an aromatase and the inhibitors which block this function are called aromatase inhibitors. Reducing the levels of oestrogen may therefore result in low amounts of oestrogen in the blood which deprive breast cancer cells of substances that it requires to function.

Choice of aromatase inhibitors

Various clinical trials have shown the aromatase inhibitors to be very useful and can be used in different settings. Sometimes, this is used on its own and others sequentially after tamoxifen. When used on its own, it is commonly described for 5 years. If used in sequence after Tamoxifen, it is usually given after 2 years of Tamoxifen for 3 years, completing a total of 5 years of endocrine treatment in total.

Patients who have completed 5 years of tamoxifen are sometimes recommended to convert to an aromatase inhibitor for a further 5 years. This is called “extended adjuvant therapy”. The commonest aromatase inhibitor to be used in this context is letrozole.

Aromatase inhibitors are sometimes used in the primary treatment of cancer, before surgery. This is often to reduce the size of the cancer to facilitate surgery or to enable a less extensive operation

Any of the Aromatase Inhibitors can be used in sequence after 2 years of Tamoxifen. The advantage of using 2 years of Tamoxifen prior to 3 years of an Aromatase Inhibitors is that Tamoxifen protects bone mass whereas an Aromatase Inhibitor may result in loss of bone, a condition called osteoporosis.

Side effects of Aromatase Inhibitors

Hot flushes and sweats. These are usually mild and many women find that these symptoms settle over the fullness of time:

- Vaginal dryness or irritation
- Low mood and concentration
- Weight gain
- Blood clots in the legs
- Bone thinning.

In women, thinning of bone in the early stages is not associated with a high fracture risk and is termed osteopaenia. Once the bone thinning continues beyond a certain level, the risk of bone fractures increases and this is termed osteoporosis. By lowering oestrogen levels the aromatase inhibitors can result in thinning of the bone. Oestrogen protects bone mass. Your doctor will monitor your bone density through your treatment and make recommendations on how to avoid inadvertent thinning of the bone or fractures.

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