Aromatase inhibitors - when to use them, toxicity and effects

By definition, aromatase inhibitors are a group of drugs that are used in the treatment of hormone-dependent female cancers. They are used in hormone therapy for breast and ovarian cancer diagnosed in postmenopausal women with ER or PGR receptors. The mechanism of action of aromatase inhibitors involves effectively reducing the activity of an enzyme called aromatase, which leads to hypoestrogenia, that is, a decrease in estrogen levels.

Hormonal cancer treatments are only used for cancers that have certain characteristics. They allow you to limit the growth of cancer cells through the use of pharmacological therapy that affects the functioning of the endocrine system. In the case of aromatase inhibitors, we are dealing with drugs whose action is based on blocking the activity of aromatase - this enzyme is responsible for the synthesis of estrogens. Aromatase inhibitors are used in the treatment of breast and ovarian cancer after specific tests have been performed to detect hormone receptors. They are less toxic than other anti-cancer drugs.

What are aromatase inhibitors and how do they work?

Aromatase inhibitors are drugs used as a complementary treatment for breast and ovarian cancer and are also sometimes used as part of breast cancer prevention in women with a history of breast cancer. They are part of the therapy of hormone-dependent cancers, i.e. cancers stimulated by hormones. In this case, we are dealing with the adverse effects of estrogens on the body.

Too long estrogen production and impaired hormone secretion can increase the risk of cancer in women, as well as stimulate the development of the disease. By blocking the synthesis of estrogens, one can obtain a therapeutic effect in the form of inhibition of cancer development.

Hormone therapy is used as an adjunct therapy in the treatment of breast and ovarian cancer. Surgical treatment, chemotherapy or radiation therapy is carried out before pharmacological therapy, which is aimed at suppressing estrogen secretion. Aromatase inhibitors are used to limit the synthesis of estrogens in adipose tissue, in the ovaries, and in endometriosis foci.

Types of Aromatase Inhibitors

There are two types of aromatase inhibitors: steroids and non-steroids. Steroid aromatase inhibitors are characterized by an irreversible effect. Exemesan belongs to this group of drugs. Non-steroidal aromatase inhibitors are characterized by reversible action. They contain letrozole and anastrozole.

Steroidal and non-steroidal aromatase inhibitors are used for other cancers in premenopausal and postmenopausal women.

Exemesan is used to treat breast cancer in premenopausal and postmenopausal women. This drug completely, irreversibly blocks aromatase activity, causing a decrease in estrogen levels in the body.

Aromatase inhibitors from the group of nonsteroidal drugs are characterized by reversible action. They do not affect the functioning of the endocrine system in a way that would be limited by the significant risk of side effects of therapy - non-steroidal aromatase inhibitors do not interfere with the secretion of other hormones, blocking estrogen secretion by 90%. They are effective in the use of specific enzymes in the treatment of breast cancer in postmenopausal and premenopausal women - in this case, it is necessary to accelerate menopause, for example, with the help of drugs.

Most often, the use of aromatase inhibitors begins after tamoxifen therapy. Aromatase inhibitors are used in accordance with ASCO (American Society of Clinical Oncology) guidelines.

The use of any aromatase inhibitor should be under the supervision of a physician and in accordance with the current hormonal treatment regimen for breast cancer. It should be remembered that this is an adjuvant treatment preceded by radiation therapy, chemotherapy or surgery.

Indications for the use of inhibitors

As already mentioned, aromatase inhibitors are used in the treatment of breast cancer and ovarian cancer. They should be used after prior consultation with a doctor and in accordance with the instructions regarding the schedule of therapy.

They are most commonly used as adjuvant therapy for early-stage hormone-dependent breast cancer, as adjuvant therapy after tamoxifen treatment, and for advanced breast cancer.

It happens, however, that an aromatase inhibitor is used contrary to its intended purpose, since it has the effect of reducing the harmful effects of anabolic steroids on the body. Anabolic steroids are a group of drugs that are used, for example, by professional athletes and figure sports enthusiasts in order to improve body proportions and obtain a muscular figure.

Thanks to aromatase inhibitors, it is possible to reduce excess body fat, avoid the development of gynecomastia, and remove subcutaneous water. These drugs convert some of the testosterone in the body (secured naturally or with the help of anabolics) into estrogen. Aromatase inhibitors are sometimes recommended as an ingredient in nutritional supplements for athletes, but their use is banned and considered doping. Detection of the presence of aromatase inhibitors or other doping drugs in the body of an athlete excludes their participation in sports competitions and is associated with other consequences.

How are aromatase inhibitors used?

Aromatase inhibitors should be used in accordance with ASCO guidelines, and the total duration of treatment with this group of drugs should be 10 years. The adjuvant regimen includes the use of tamoxifen and aromatase inhibitors in certain combinations, depending, for example, on whether the woman has gone through menopause.

Treatment regimen for patients without menopause

Women diagnosed with premenopausal breast cancer at the start of adjuvant hormone therapy should receive tamoxifen. The inclusion of aromatase inhibitors in the treatment regimen is possible after the patient has experienced menopause. The passage of menopause must be confirmed by tests.

Treatment regimen for postmenopausal patients

Women diagnosed with hormone-dependent breast cancer after proven menopause are eligible for adjuvant therapy with tamoxifen as well as an aromatase inhibitor; it is possible to use anticancer hormone therapy, taking into account the interchangeability of these drugs.

Additional hormonal therapy for breast cancer should be continued for 10 years, taking into account possible combinations of drugs recommended by ASCO, i.e.:

• 10 years tamoxifen,

• 5 years tamoxifen + 5 years aromatase inhibitor,

• aromatase inhibitor 5 years + tamoxifen 5 years,

• 2-3 years tamoxifen + 5 years aromatase inhibitor,

• Aromatase inhibitor for 5 years.

In some cases, the use of tamoxifen is not possible due to contraindications and side effects, which include, among others:

• drug allergy,

• varicose veins and thrombosis,

• depression,

• cataract.

The inability to use tamoxifen is an indication for starting treatment with aromatase inhibitors. If the treatment concerns premenopausal women, it should be prompted by appropriate drugs. In the presence of contraindications to treatment with aromatase inhibitors and the possibility of using tamoxifen, it is administered during the entire period of adjuvant therapy.