Study Reveals Unique Alzheimer's Risks and Resilience in Women After Ovarian Removal - Video

New research published by a team of researchers from the University of Toronto in collaboration with colleagues from the University of Alberta has found that women who have had both ovaries surgically removed before the age of 50 and carry a variant of the apolipoprotein gene, the APOE4 allele, are at high risk of late-life Alzheimer disease (AD). The use of hormone therapy mitigates this risk.

The researchers analyzed a cohort of 34,603 women from a large dataset, the UK Biobank, and found that in this cohort, women who had had both ovaries surgically removed (bilateral oophorectomy) at the approximate age of 43 showed four times the odds of developing Alzheimer’s disease when compared to women who entered natural menopause at a mean age of 54. The paper was published online in the

Journal of Alzheimer’s Disease.

“One of our most important findings was the fact that loss of the naturally occurring hormone (endogenous), estradiol, as a result of surgical removal of both ovaries, might interact with the APOE4 allele to further increase Alzheimer’s disease risk, placing women with early bilateral oophorectomy and APOE4 in a state of double jeopardy,” said Dr. Einstein. APOE4 is a known risk factor for Alzheimer’s disease in the general population but presents a greater risk in women.

The study also identified resilience factors associated with the risk of Alzheimer’s disease for these women. A high level of education was linked to a 9% lower likelihood of developing Alzheimer’s disease in women with both types of menopause — that caused by ovarian removal and that caused by aging — supporting previous research showing education as a form of cognitive resilience in both women and men.

Surprisingly, there was also a modest relationship between body mass index (BMI) and Alzheimer’s disease risk, but only for women with early bilateral oophorectomy. Each additional unit of BMI was associated with a 7% lower risk of developing Alzheimer’s disease.

Importantly, among women with early bilateral oophorectomy, ever taking hormone therapy was associated with less than half the odds of Alzheimer’s disease compared to those women who had not taken hormone therapy.

Reference: Calvo N, McFall GP, Ramana S, et al. Associated risk and resilience factors of Alzheimer’s disease in women with early bilateral oophorectomy: Data from the UK Biobank. Journal of Alzheimer’s Disease. 2024;102(1):119-128. doi:10.3233/JAD-240646