Estrogen-modulating therapy may reduce risk for Alzheimer’s disease

Tamoxifen and steroidal aromatase inhibitor use among women with breast cancer was associated with a significantly lower risk for Alzheimer’s disease, a retrospective cohort study showed.

“Our lab has helped to develop a link between the decrease in estrogen status seen in women during menopause to the increased risk for Alzheimer’s disease in women overall in this age group,” Gregory L. Branigan, an MD‐PhD candidate from the Brinton Lab at the Center for Innovation in Brain Science at the University of Arizona Health Sciences, told Healio Primary Care.

“Along this line of thinking, we were interested in therapeutics that target estrogen, such as those used in the treatment of breast cancer, and what impact these might be having on future AD risk in this clinical population,” he said. 

Branigan and colleagues analyzed health insurance claims from Humana’s database that were filed from 2007 to 2017. They looked for a neurodegenerative disease diagnosis any time starting 1 year after a woman’s breast cancer diagnosis and receipt of estrogen modulating therapies (eg, tamoxifen, raloxifene and steroidal aromatase inhibitors). The analysis included data from 57,843 propensity score-matched perimenopausal- to postmenopausal-aged women.

The researchers reported that exposure to tamoxifen and steroidal aromatase inhibitors was associated with a significant decrease in diagnosis of Alzheimer’s disease (RR = 0.827; 95% CI, 0.759-0.901). The researchers also found that the reduction in neurodegenerative disease risk increased with age.

Branigan called the results “very surprising and interesting.”

“Previous to this study, there was very little known about how these therapeutics impact the brain specifically and the mechanisms by which they may impact risk of Alzheimer’s disease,” he said. “Our findings are suggestive that these agents may be working in a pro‐estrogen mechanism, as opposed to their anti‐estrogen action seen in breast tissue.”

According to Branigan, the findings also provide “the framework and proof of concept” that treatment discussions can include the neurological impact of therapeutic agents for systemic disease.

“There is an increasing number of patients who are at risk for neurodegenerative disease [and] who will be prescribed medications,” he said. “We have an opportunity to advance precision prevention by understanding the differences in how a given class of therapeutics can affect the brain.”