Estrogen and the Aging Brain

by Clinical Consulting Team

A growing body of research suggests estrogen levels throughout a woman’s life may influence her risk of developing Alzheimer’s disease. In this case, more estrogen appears to be better.

Alzheimer’s disease is the 5th leading cause of death in the elderly in the United States and is increasing in incidence. Furthermore, among those over 75, it is the second leading cause of death, just behind cardiovascular disease. Those suffering from Alzheimer’s experience intense isolation and depression, and long-term care is dramatically more expensive than other common serious conditions. Although there have been medications approved for treatment of Alzheimer’s since 1993, prevention or cure of the disease remains elusive.

When researchers have looked into health histories of large groups of women, an interesting pattern appears. Life events demonstrate that greater exposure to estrogen throughout a woman’s life may be linked to a decrease in Alzheimer’s. Events such as when she starts her first menstrual cycle (earlier is better), how many pregnancies she has (more are better) and how late she goes into menopause (later is better) can affect a woman’s risk. These findings have led researchers to explore the potential benefits of estrogen therapy for lowering Alzheimer’s risk. However, early in life menstrual cycles and late menopause increase a woman’s risk for breast cancer, so caution should be used when assessing the appropriateness of hormone therapy.

Currently estrogen replacement therapy is not recommended for prevention of Alzheimer’s disease. However, a study looking at deceased females found that those who used estrogen for menopause symptoms were significantly less likely to have had a diagnosis of dementia or Alzheimer’s. More convincingly, in those who used higher doses of estrogen for longer periods, the benefit was more pronounced. Women who start estrogen replacement therapy more than 10 years after the onset of menopause had no benefit, which indicates that estrogen deprivation for several years may have irreversible impact on brain health.

The most common reasons women seek out hormone testing in perimenopause are hot flashes, low mood, weight gain, brain fog and decline in memory. Research shows these symptoms to be primarily symptoms of low estrogen in the brain. Health care providers might consider symptoms of cognitive decline a good reason to test sex hormones. Testing sex hormones and monitoring symptoms during peri- and post menopause remains an effective way to assess estrogen and estrogen therapy’s long-term health for the brain and body. DUTCH testing shows not only the patient’s estrogen levels but how they are metabolizing estrogen, which can be helpful in lowering the risks of hormones as in breast cancer.

What about Men? It appears that estrogen benefits men’s neurological health, too. Although testosterone decline is common as men advance in age, men do continue to make testosterone throughout their natural life. Due to aromatization, men typically have higher estrogen in their later years than post-menopausal women. In healthy men who are not on hormones, there are no events of significant estrogen decline equivalent to menopause in women. However, some older men do experience low testosterone, and possibly concurrently low estrogen.  This highlights the importance of testing men to make sure their estrogen is in range (not too high or low).  This may be particularly necessary if the men are on exogenous testosterone (which may get converted to estrogen) or an aromatase inhibitor (which blocks estrogen production).

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Resnick, S.M. and V.W. Henderson, Hormone therapy and risk of Alzheimer disease: a critical time. JAMA, 2002. 288(17): p. 2170-2.

Janicki, S.C. and N. Schupf, Hormonal influences on cognition Maki, P.M., et al., Perimenopausal use of hormone therapy is associated with enhanced memory and hippocampal function later in life. Brain Res, 2011. 1379: p. 232-43.and risk for Alzheimer’s disease. Curr Neurol Neurosci Rep, 2010. 10(5): p. 359-66.