Can Hormone Replacement Therapy Protect Against Alzheimer’s?

Alzheimer’s is a debilitating disease that affects many people as they age. Research suggests that hormone replacement therapy could reduce the risk of neurodegenerative diseases, and that this reduction in risk varies depending on the type of hormone therapy, how it’s administered, and how long it lasts. These findings could lead to the development of a precision medicine approach to prevent neurodegenerative diseases.

The Role of Estrogen in the Brain

Researchers estimate that nearly two-thirds of Alzheimer’s patients are women. The higher prevalence of Alzheimer’s in women may be due in part to women’s longer lifespans. A leading hypothesis is that this susceptibility is related to estrogen. The drop in estrogen levels that occurs with menopause leads to a decrease in the volume of “grey matter,” brain cellular matter (GMV), in key brain regions that are also affected by Alzheimer’s disease. A study by Weill Cornell Medicine researchers in collaboration with the University of Arizona suggests that greater cumulative lifetime exposure to estrogen, such as from having more children or from hormone therapy during menopause, may counteract this brain-shrinking effect.

Receptors for estrogen molecules are found in all brain cells in women, and the sex hormone has long been known not only to help guide brain development and behavior, but also to play a nourishing and protective role in the central nervous system more generally. However, this protection does not last forever. Estrogen levels drop precipitously during the transition to menopause, and recent research has shown that women tend to experience significant gray matter loss during this transition.

Estrogen to Protect Brain Regions Prone to Alzheimer’s

The analysis included 99 women aged 46 to 58 years and a comparison group of 29 men of the same age. She confirmed that postmenopausal and perimenopause (onset of menopause) women have significantly lower gray matter volumes – adjusted for age and head size – in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions compared to premenopausal women and men, who are severely affected by Alzheimer’s.

In contrast, in women, higher estrogen exposure, as implied by various factors, was associated with higher gray matter volume in certain brain areas. For example, a longer reproductive span was significantly associated with more GMV in a group of regions near the top of the brain, including the superior parietal lobe and the precuneus of the left hemisphere. Having more children was significantly associated with more GMV in the inferior and middle frontal gyri and the middle and inferior temporal gyri. Use of hormone replacement therapy was associated with more GMV in the superior frontal gyrus and several other brain regions. All of these brain regions are known to be affected by aging and Alzheimer’s.

The findings support the idea that estrogen may be protective, the researchers said, and suggest that further investigation of the specific biological pathways underlying this effect could lead to medical or lifestyle changes that help women to manage their risk of cognitive decline with increasing age and Alzheimer’s dementia.

Types of Hormone Replacement Therapy

A study published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions found that women who had been on menopausal hormone therapy for six years or more were 79% less likely to develop Alzheimer’s disease. The risk of developing a neurodegenerative disease was reduced by 77%.

During the study, researchers examined the insurance claims of nearly 400,000 women ages 45 and older who were going through the menopause. They focused on the effects of individuals from the U.S. Food and Drug Administration-approved hormone therapy drugs, including estrogens and progestins, and combination therapies for neurodegenerative diseases. In addition, they assessed the effects of the type of hormone replacement therapy, the route of administration – oral vs. through the skin – and the duration of therapy on the risk of developing the disease.

They found that using the natural steroids estradiol or progesterone resulted in greater risk reduction than using synthetic hormones. Oral hormone therapies resulted in a reduced risk of composite neurodegenerative diseases, while dermal hormone therapies reduced the risk of developing dementia. The overall risk was reduced most in patients aged 65 years and older. In addition, the protective effect of long-term therapy of more than one year in Alzheimer’s, Parkinson’s and dementia was greater than that of short-term therapy of less than one year. Reducing the risk of Alzheimer’s, Parkinson’s and dementia means these diseases share a common driver, which is estrogen regulated, and when there are common drivers, common therapies can be possible.

Conclusion

Hormone replacement therapy is considered an effective treatment in fighting the symptoms of menopause, which include hot flashes, night sweats, insomnia, weight gain and depression. While such therapy offers a number of benefits, it can also pose some risks. Temporary symptoms, which usually disappear again, mainly include water retention, spotting and nausea. Long-term hormone therapy over years can increase the risk of thrombosis, breast cancer and liver disease, especially when given orally. For this reason, it is important to carry out a benefit-risk assessment together with yor doctor in order to decide whether this form of therapy is an option for you.