A new study published in PubMed looked at the associated risk and resilience factors of Alzheimer’s disease in women with early bilateral oophorectomy.
“The study is about risk and resilience factors related to Alzheimer’s disease (AD) in women,” study author Noelia Calvo told us. “Epidemiologic data show that AD is more prevalent in women than in men, but we do not know why. We were hoping to understand the possible risk and resilience factors for AD specifically in women with early bilateral oophorectomy- removal of both ovaries that leads to surgical menopause.”
The main hypothesis of the study was that women with surgical menopause would have greater risk for AD than women with spontaneous menopause. The researchers included in their model other relevant variables such as carrying the APOE4 allele, hormone therapy, and other sociodemographic information. The idea was to predict the possible risk of oophorectomy for AD, as well as the possible factors that might improve women’s brain health irrespective of the presence of pathological aging.
“At the Einstein lab (The Einstein Lab – Cognitive Neuroscience, Gender and Health), we are investigating molecular, biological and social factors that might affect women’s health and explain some of the reasons why two thirds of the people diagnosed with AD are women,” Calvo told us. “Our data indicate that estradiol loss due to menopause might be one of these factors because this hormone is a potent neurotrophic factor in the adult brain. The problem is that there are ‘many menopauses’ and previous research has mainly focused on one type of menopause which is what we call ‘spontaneous menopause’ that happens due to aging at around 51 years of age. We were interested in understanding the effects for AD in younger women with early surgical menopause; the removal of both ovaries at around age 42 which leads to an abrupt loss of estradiol.”
The research team accessed the UK Biobank cohort which is a prospective population-based database of more than 500,000 individuals with extensive phenotypic and genetic data. This allowed them to analyze risk and resilience factors for AD in women with menopause in a very large cohort. They included women aged 60 + at baseline with and without AD who had early oophorectomy or spontaneous menopause. They then used logistic regression to model the association of menopause type with AD. The predictors for the model included age, education, age at menopause, hormone therapy (HT), APOE4, body mass index (BMI), cancer history, and smoking history.
“In comparison to spontaneous menopause, early oophorectomy increased the odds of AD incidence,” Calvo told us. “The results also showed a link between the APOE4 allele and surgical menopause; women with both APOE4 and ovarian removal had a fourfold increased risk for AD. But hormone therapy reduced this risk by almost half. We also identified other resilience factors. For instance, a high level of education was linked to a 9% lower likelihood of developing AD in women with both types of menopause.”
A fourfold increase in the odds of AD is high which highlights the importance of estradiol loss at a young age. There was also a modest relationship between body mass index (BMI) and AD risk, but only for the women with early bilateral oophorectomy. Each additional unit of BMI was associated with a 7% lower risk of developing Alzheimer’s disease.
“This was surprising because we tend to think of higher BMI as a risk for many other diseases,” Calvo told us. “But a higher BMI might be associated with a decreased AD risk particularly in this cohort because adipose tissue produces estrone (one of the three endogenous estrogens) which, in the absence of estradiol due to oophorectomy, may help maintain cognitive function in early middle age. This result should be taken with cautions as further research is needed to understand these mechanisms.”
The research team thinks the results are important because they are about a specific type of menopause and show clear effects of hormone therapy for this group of women alone. There has been a debate in the field around whether to use hormone therapy or not for menopause. The literature is complex and shows contradictory results because most studies have not specified which type of menopause their results refer to, or they have only focused on spontaneous menopause.
“We found that women with early oophorectomy who carry the APOE4 allele show a fourfold increase in the risk for AD, but estradiol therapy reduces this risk by half,” Calvo told us. “Thus, our results highlight the importance of precision medicine research. By specifying type of menopause, we can clearly identify risk and resilience factors for AD. Importantly, our results are in accordance with the current position statement by the North American Menopause Society (NIAMS) which recommends hormone therapy only for young women with oophorectomy.”