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URMC / Obstetrics & Gynecology / UR Medicine Menopause and Women's Health / menoPAUSE Blog / May 2020 / I am 53 years old and losing my memory. My last menstrual period was two years ago. In those two yea

I am 53 years old and losing my memory. My last menstrual period was two years ago. In those two years, my memory has gotten terrible. Is this related to loss of hormones?

Your Question: I am 53 years old and losing my memory. My last menstrual period was two years ago. In those two years, my memory has gotten terrible. Is this related to loss of hormones?

Our Response: Our understanding of memory has advanced through animal studies of the mouse, rat, and monkey, but the results are applicable to humans, and estradiol plays a key role in this process.

Within the brain, the hippocampus and median pre-frontal cortex represent the centers for acquiring and retaining short- and longterm memory. However, it all begins as an electrical change in a single neuron, mostly likely in the hypothalamus; what follows is a series of structural changes leading to progressive communication across neurons.

Memory depends on “synaptic plasticity” for acquiring, consolidating, and retaining memory. This term refers to the ability of a neuron to develop and maintain spine-like protrusions on its dendrites (the branches that radiate out from the body of the neuron). It is these dendritic spines that allow information to be passed from one neuron to the next. So why is estradiol important? The answer has an impact on menopause management, breast cancer, and Alzheimer’s disease.

Dendritic spines are highly sensitive to estrogen fluctuations. Density of dendritic spines is highest when estradiol is plentiful and decreases when estradiol is not available. This relationship has been demonstrated in animal models surgically thrown into menopause by the removal of their ovaries. Loss of estradiol leads to rapid reduction in dendritic spines. Yet, when estradiol is reintroduced into the animal models, dendritic spines reappear, in some cases as quickly as 30 minutes, showing the dynamic characteristics of this process.

The direct correlation of estradiol loss to memory loss now is well established. Other clinical outcomes support this premise. When women with estrogen-positive breast cancer are put on an aromatase inhibitor to block the body’s production of estradiol, their “brain fog” most likely is explained by loss of estradiol and dendritic spine function.

Autopsies of patients dying of Alzheimer’s disease show reduced dendritic spines. When amyloid, which is deposited in the brains of Alzheimer patients, is inserted in animal brains, it causes dendritic spines to shrink. Yet, studies have shown that estradiol, administered in early menopause, reduces the incidence of this debilitating form of dementia. Estradiol improves blood flow to the brain, thus, delivering much needed glucose to serve the brain’s need for fuel. It also offers anti-inflammatory effects. It is likely that a third benefit of estradiol, especially started before menopause has advanced, is to maximize dendritic spine formation.

The biology of hormone replacement therapy is advancing at an incredible rate. And many of the health issues that once were thought of as singular events are now being grouped as our body’s hormone profile changes. Keeping up with these advances is a challenge to care providers, but an asset to women’s health.

James Woods | 5/20/2020

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