Aromatase Inhibitors: Side Effects Revisited

by Brenda Salgado

Women facing a life-threatening illness often have very difficult decisions to make about their treatments and whether or not they can live with the side effects of what could be a helpful drug. For postmenopausal women living with estrogen-receptor-positive breast cancer, aromatase inhibitors (AIs) are a relatively new class of drugs that have quickly become the standard of care.

Arimidex, the first AI, was approved by the FDA in 1996 for breast cancer treatment. Soon after, BCA started hearing from women whose doctors were recommending Arimidex, asking what the known side effects were and how long they should stay on the drug. The other two AIs that were subsequently approved are letrozole (Femara) and exemestane (Aromasin).

While some information about AI side effects is available, a great deal is still unknown about their long-term effects. Knowing that the FDA couldn’t—and the drug industry wouldn’t—collect this information in a way that’s helpful to patients, we decided to do it ourselves.

Breast Cancer Action (BCA) launched an online survey in 2005 to collect information from women about AI side effects they were experiencing. In 2007, we released a preliminary report, and in June 2008 we released a follow-up report.

The new report, Side Effects Revisited: Women’s Experiences with Aromatase Inhibitors, was based on nearly 1,200 responses. Almost all the women reported experiencing at least one of the 38 side effects listed in the survey. The most common side effects—reported by more than half of survey respondents—continue to be hot flashes, bone pain, tiredness, muscle pain, and insomnia. Particularly troubling was the finding that more than 25 percent of respondents experienced side effects so severe they decided to stop taking their AI. The most commonly cited cause for discontinuing their therapy was pain (joint-related, bone, muscle, vaginal, bladder or chest pain).

The report also found that the women who took our survey were, on average, much younger than the women who have been studied in clinical trials of these drugs. (The report is not necessarily a representative sample of all women taking an AI.) These younger women—and by younger we mean under 60—were experiencing more and worse side effects than older women on AIs. This is particularly true for younger women whose menopause was medically-induced.

As a result, some of these women were experiencing very real quality-of-life issues that weren’t reflected in clinical trial data thus far. Age—either alone or in conjunction with treatment (induced menopause or prior tamoxifen use)—appears to be related to the incidence and severity of the AI side effects the women reported experiencing. These results tell us that it will be crucial for future studies to look at how AIs are affecting younger women.

Compared to women who became menopausal naturally, a significantly greater percentage of the women whose menopause was induced reported swelling of their arms and legs, hair thinning, hot flashes, and weight gain. The incidence and severity of these side effects may be related to the sudden and premature onset of menopause in younger women.

Our results indicated that a larger percentage of women who had not previously taken tamoxifen experienced a number of side effects (insomnia, bone pain, mental fuzziness, muscle pain, diarrhea, shortness of breath, flu-like symptoms, headaches, and vomiting) as compared to women who had taken tamoxifen prior to an AI. BCA’s report cites a 2007 study in The Lancet,which suggests, “Early exposure to tamoxifen would…through its oestrogenic effects, ameliorate some of the adverse effects of aromatase inhibitors, such as excess calcium loss.” The youngest women (20- to 39-year-olds) were significantly less likely to have taken tamoxifen prior to taking an AI, as compared to the older age groups.

Preliminary analyses of the data have yielded results that, overall, are similar to results in our first report. Based on these findings, we have decided to discontinue the survey. However, BCA remains concerned that there may be long-term side effects from AIs that cannot be documented for several years, as was the case with tamoxifen. BCA will continue to monitor the literature about AIs, and we encourage women to share their experiences with us.

Here at BCA, we understand that patients almost always know—before the medical community does—what side effects they are experiencing. We encourage additional research on the long-term side effects for all women taking these drugs. After all, this information is what allows people to make informed decisions about their health care—a value that’s critically important to all of us.

Read the report

The report is dedicated to the women who generously took the time to respond to BCA’s Aromatase Inhibitor Side Effects Survey and to everyone who seeks to make informed decisions about the care they receive.


This entry was posted in Articles.