Menopause: The Potential Missing Link in Women’s Susceptibility to Alzheimer’s Disease

Dr. Singh presented his talk on “The Neurobiology of Estrogens, Progestins, and Androgens: Implications for Brain Aging, Neurodegenerative Disease and Brain Tumors.” The effects of gonadal hormones, such as estrogen and progesterone, extend beyond the reproductive system, and the brain is a key target of these hormones. Menopause causes a steep decline in levels of progesterone and estrogen, which leads to women spending approximately a third of their lives in an estrogen- and progesterone-deprived state. In addition, women have about a 3-fold higher prevalence of Alzheimer’s than men. Estrogen has been shown to protect neurons from circumstances that are related to neurodegenerative diseases, and progesterone has a neuroprotective function along with activating survival promoting pathways.  

The article by Pincott (2020) describes research by Mosconi et al. (2018), who found that brain glucose metabolism slows by 20 to 30 percent in post-menopause due to a decrease in estrogen, which has a role in regulating brain metabolism. According to the menopause hypothesis, decline in estrogen levels during menopause could leave the brain more vulnerable to damage, leading to women having a one-in-five lifetime chance of developing Alzheimer’s disease. Compared to women in their 40s and 50s, the brains of males in the same group do not age significantly in the same way. This may be because testosterone also functions as a neuroprotective factor; however, unlike estrogen and progesterone, levels of testosterone do not drop significantly with age. However, studies in recent years have shown differing results in the usefulness of hormone therapy (estrogen and progestin), ranging from a 30 percent reduction in Alzheimer’s risk to a 9-17 percent increase in Alzheimer’s risk. 

The findings of Nguyen et al. (2018) indicate that the microRNA let-7i disrupts Progesterone-induced neuroprotection following ischemia (stroke). Potential further applications of these findings may be the discovery of specific biomarkers that predict those who are likely to respond favorably to treatment with Progesterone. This information may be an important missing piece in the work described in Pincott (2020), which describes studies of hormone therapy in protection against later development of Alzheimer’s disease. Studies using hormone therapy treatment in humans have been inconclusive as to the usefulness of the therapy. The discovery of certain biomarkers that modulate the neuroprotective effects of progesterone during ischemia may also indicate the presence of certain biomarkers that modulate the neuroprotective effects of progesterone and estrogen to prevent the development of Alzheimer’s disease. The discovery of these biomarkers could lead to breakthroughs in hormone therapy treatment, which would allow researchers and clinicians to determine which patients would benefit from neuroprotective treatment with supplemented progesterone and estrogen. 

 

References 

Nguyen, T., Su, C., Singh, M. (2018). Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia. PNAS, 115(41), E9668-E9677. www.pnas.org/cgi/doi/10.1073/pnas.1803384115.  

Pincott, J. (2020). Menopause predisposes a fifth of women to Alzheimer’s. Scientific American. https://www.scientificamerican.com/article/menopause-predisposes-a-fifth-of-women-to-alzheimers/.