Side Effects of Aromatase Inhibitors

Bone loss

Aromatase inhibitors cause a drop in the amount of the estrogen reaching bone cells. Estrogen tells bone cells to build new bone to make up for the steady loss of bone that happens naturally as we age. As aromatase inhibitors lower estrogen levels, bones can become thinner and weaker over time. If bones lose a lot of strength, resulting in osteoporosis the risk of breaking a bone increases.

Your risk for significant bone thinning depends on:

• the strength of your bones before you got started on hormonal therapy.
• how long you take aromatase inhibitors, since this treatment causes loss of bone over time.
• other risk factors for bone thinning, which including being thin, being white, smoking, and having a mother, father, brother, or sister with a history of osteoporosis.
• whether you also take bone-strengthening medicines while undergoing hormonal therapies that cause bone loss. Some doctors now routinely recommend taking a bone-strengthening medication for all women who take an aromatase inhibitor.

One major study, called Z-FAST, found that Zometa (chemical name: zoledronic acid), a bone-strengthening medicine, resulted in improved bone mineral density (BMD) of the spine and hip after one year in women who were taking Femara (chemical name: letrozole), an aromatase inhibitor.

The Z-FAST study included only post-menopausal women with early-stage hormone-receptor-positive breast cancer. Half of the women began taking Zometa as soon as they started Femara. The other half didn't start Zometa until several months later. Researchers are comparing the BMD at the spine and the hip for the two groups of women over a period of five years.

After one year, the women who delayed taking Zometa had lost significantly more BMD at the spine and hip than those who started taking Zometa when they began taking Femara. Stay tuned to Breastcancer.org for updates on the Z-FAST trial.

Other side effects of aromatase inhibitors

In addition to bone loss, other side effects are seen more often in women taking aromatase inhibitors than in those taking tamoxifen or a placebo (dummy) pill:

• Sore muscles, joint pain, and arthritis. All three aromatase inhibitors (Arimidex [chemical name: anastrozole], Aromasin [chemical name: exemestane], and Femara) have been shown to result in a 3-4% increase in complaints of sore muscles or joint pain compared to tamoxifen or a placebo (dummy pill).
• Increase in cholesterol levels. Both Femara and Arimidex have been shown to increase blood cholesterol levels. Researchers are currently studying the long-term impact of this side effect. Since high cholesterol levels are associated with an increased risk of heart disease over time, there is concern that aromatase inhibitors might increase your risk for heart problems. If you have a family history for heart disease or have other risk factors, make sure you and your doctor watch your cholesterol level carefully. You might need to take steps to lower your cholesterol with weight control, a low-fat diet, exercise, and possibly cholesterol-lowering medication.
• Stomach upset and mild nausea. Nausea usually occurs in the first weeks of treatment and then slowly go away.

Overall, the aromatase inhibitors have relatively few serious or unmanageable side effects. Keep in mind that the number of people who have side effects with all the aromatase inhibitors, and particularly Arimidex, is low. Less than 1% of women will have side effects that require stopping the drug.