Dementia and Alzheimer's Disease Associated With Aromatase Inhibitors: A Disproportionality Analysis of the WHO Pharmacovigilance Database (VigiBase)

Abstract

Aromatase inhibitors are used for patients with hormone-receptor positive breast cancer. Alzheimer's disease is the most prevalent cause of dementia. Several studies have suggested an association between the use of aromatase inhibitors and the development of Alzheimer's disease. The objective of this study was to identify potential pharmacovigilance signals associated with dementia and Alzheimer's disease and third-generation aromatase inhibitors in menopausal and postmenopausal women. VigiBase, the global database of individual case safety reports of the World Health Organization, was used to investigate this possible association. A disproportionality analysis was performed for women aged 45 years and older. The reporting odds ratio (ROR) and its 95% CI for reporting dementia are exemestane, 2.08 (1.35–3.19); anastrozole, 1.59 (1.09–2.32); and letrozole, 1.43 (1.05–1.95) and for Alzheimer's disease are exemestane, 0.94 (0.30–2.92); anastrozole: 2.63 (1.55–4.45); and letrozole, 1.33 (0.76–2.35). For senile dementia, only letrozole has cases, with an ROR of 6.77 (2.51–18.31). Signals of disproportionate reporting have been observed between the occurrence of dementia, dementia Alzheimer's type, and senile dementia with aromatase inhibitors, which is in line with estrogen functions and aromatase activity, as well as the findings from preclinical studies. Additional research is required to elucidate this intricate matter.