Although diabetes and blood sugar level increases are not listed as a side effect of letrozole treatment, treatment with letrozole does appear to be associated with a significantly increased risk for high blood sugar levels and diabetes. An Israeli study that investigated 2,246 breast cancer survivors found that women treated with letrozole were 4.3 times more likely to develop diabetes than women not taking letrozole, although the number of women prescribed letrozole was small. Overall, women prescribed any sort of hormone treatment (either tamoxifen or an aromatase inhibitor such as letrozole) had a 2.5 times higher risk of diabetes. Women who developed diabetes during the study were also:

• much more likely to be obese
• much less likely to exercise
• much more likely to eat an unhealthy diet.

Women in the study were followed for approximately 6 years and the rate of diabetes diagnosed rose from 6% in 2002 at the start of the study to 28% when the study ended in 2015.

Worry about developing high blood sugar levels and diabetes should not be a reason women should avoid hormone treatment such as letrozole because the survival benefits far outweigh the risks. But it is important women treated with hormone therapy should be closely monitored for high blood sugar levels and diabetes. In addition, eating a healthy diet, exercising, and not smoking can all help reduce the risk of diabetes developing.

The researchers of the study weren’t sure why letrozole was associated with a higher risk of diabetes but suggest that estrogen deficiency caused by letrozole enhances metabolic dysfunction and predisposes to obesity and progression of the metabolic syndrome, well-established risk factors of diabetes. Estrogens are also protective against insulin resistance, which is central to the development of diabetes. Letrozole markedly suppresses estrogen levels in postmenopausal women by inactivating the aromatase enzyme responsible for the synthesis of estrogens from androgenic substrates; therefore, their effect on estrogen levels is more pronounced than that seen with tamoxifen.