Aromatase inhibitors, which include Arimidex (anastrozole), Femara (letrozole), and Aromasin (exemestane), generally are used to treat estrogen receptor positive (ER+) breast cancer in postmenopausal women. These anti-estrogen drugs have a number of potential side effects, including weight gain.

Weight gain is common, but not inevitable

Weight gain is common among women being treated with aromatase inhibitors. This is also true of those using tamoxifen as anti-estrogen treatment. Most studies have found no significant difference in weight gain between the three major aromatase inhibitors or between aromatase inhibitors and tamoxifen among postmenopausal women. Any weight gain typically occurs mostly within the first 12 months of treatment.
While weight gain is common, most women treated with aromatase inhibitors do not gain weight. One study reported that 39% of study participants had gained over 2 kg (4.4 lb), 27% had lost more than 2 kg, and 34% had stable weight after two years of endocrine treatment (i.e., either tamoxifen or an aromatase inhibitor). Type of treatment did not make a difference in weight change results. Another study found that 34% of survivors had experienced weight gain of at least 5% after five years of endocrine treatment.
Still another study that focused only on aromatase inhibitor treatment reported that after an average of 23 months, 27% of the study participants had gained weight (at least 10 lb), 11% had lost weight (at least 10 lb), while 61% had maintained their weight (±10 lb).
Importantly, aromatase inhibitor treatment is often accompanied by a change in body fat distribution, whether or not weight is gained. One study reported that the treatment resulted in a higher VAT/SAT ratio, the ratio of visceral (abdominal) to subcutaneous fat. Higher abdominal fat is associated with metabolic disorders such as insulin resistance and high cholesterol.

Reason for weight gain on aromatase inhibitors

Weight gain while on an aromatase inhibitor is not a simple matter of increased appetite. The manipulation of estrogen receptor (ER) signaling by endocrine treatments helps prevent ER+ breast cancer growth but also has some consequences that are not beneficial for patients. Among them are a tendency to interfere with fat cell development, promoting the formation of extra-large fat cells. This leads indirectly to increased circulating insulin, insulin resistance, and glucose intolerance, all of which encourage weight gain (and the development or worsening of type 2 diabetes).

Consequences of aromatase inhibitor weight gain

As noted above, weight gain while undergoing aromatase inhibitor treatment is associated with increased risk of type 2 diabetes, which has a variety of adverse health effects and is itself a breast cancer risk factor. However, whether gaining weight during aromatase inhibitor treatment increases risk of breast cancer recurrence is not clear.
One study reported that weight gain appeared to result in reduced effectiveness of Femara as a result of the development of increased circulating insulin. However, other studies have not found a difference in breast cancer-free survival among patients who gain weight on aromatase inhibitors and those who do not. The beneficial treatment effects of aromatase inhibitors may overcome the potentially negative effects of gaining weight on breast cancer recurrence.
The estrogen deficiency induced by aromatase inhibitors can cause an increase in vasomotor symptoms such as hot flashes and night sweats. Weight gain has been found to increase both the number and severity of hot flashes.

Preventing weight gain on aromatase inhibitors

Exercise appears to be the best strategy to prevent aromatase inhibitor-associated weight gain and body fat distribution changes. One study reported that a combined resistance and aerobic exercise program succeeded in improving body composition in breast cancer survivors taking aromatase inhibitors.
Adopting an eating plan based on our webpage Foods to eat and avoid during aromatase inhibitor treatment has the potential to improve survival while avoiding weight gain.
It is important not to use estrogenic supplements such as soy isoflavones, licorice root or red clover to reduce aromatase inhibitor side effects. To the extent that these are successful in counteracting the estrogen deprivation caused by aromatase inhibitors, they may also extinguish their treatment effects.
Please also see the following articles on aromatase inhibitors: