The aging of a human is inevitable and puts us at risk, especially during the menopausal transition in women. Menopause is a natural end to a women’s ability to reproduce and during this the ovaries produce less estrogen and progesterone. Women spend a third of their life in an estrogen and progesterone deprived state. In a study conducted by Dr. Meharvan Singh it was found that progesterone was protective in the brain and regulates the BDNF levels. BDNF or Brain-derived neurotrophic factors are lower in women after menopause, and these levels are negatively correlated with depression scores and memory. Progesterone was also found to elicit the activation of survival promoting pathways. In rats it was found that when the ovaries were removed, cognition and learning went down, but when given estradiol again it was found to increase or go back to normal. Therefore, it was found that Estrogen enhances cognitive performance, and estradiol can activate ERK/MAPK pathway. This led to the studying of hormone therapy in women for brain performance. Many population-based studies have highlighted the substantial difference in the prevalence of Alzheimer’s disease in women in comparison to men. In the findings and testing of hormone therapy however there was a key question posed: Is there a critical window for the efficacy of estrogen and progesterone therapy? Is it a function of age or duration of hormone loss or consequence of pathology? In a recent study titled “The Role of Estrogen Therapy as a Protective Factor for Alzheimer’s Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature” the researchers examined estrogen therapy in regard to the “The window of opportunity theory”.
Dementia is a collection of disorders marked by impairment of at least two brain functions, including judgment and memory loss. The prevalence of dementia rises from 1.5% in the sixth decade of life to 40% in the ninth, which is very concerning. Numerous studies suggest that there is a "Window of Opportunity" or ideal time to prescribe hormone therapy that improves post-menopausal women's cognitive outcomes. This was found to be during the perimenopause stage or immediately after menopause, more specifically during the first 5 years. Stronger cognitive performance and a lower incidence of Alzheimer’s disease are linked to a longer premenopausal period. For each month of estrogen exposure prior to menopause, the risk of AD decreases by 0.5%.
Many researchers have confirmed and studied hormone therapy to offset dementia and Alzheimer’s disease in women. In the research article “Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease” the researchers directly examined menopausal hormone replacement therapy and whether it has an impact on the Alzheimer’s Disease biomarker in diagnosed menopausal women. This study was the first of its kind to follow healthy women that were going through menopause and that hadn’t used hormone therapy before. To perform this and observe the progression of Alzheimer’s disease in these women, the researchers took measurements of many blood indicators in the women. The women were given the option of taking estrogen supplements orally or transdermally. If a woman chose oral estrogen, estradiol valerate 1 mg (Progynova 1 mg once daily) was prescribed. If a woman chose to take hormones transdermally, an estrogen gel (Oestrogel two doses per day) or spray (Lenzetto two spray applications per day) was prescribed. Through this they were able to find that in comparison to women who didn’t undergo hormone therapy, those who did exhibited fewer variations associated with AD. The effects of the hormone therapy were also more apparent in certain women. These women all had the gene known as APOE ε4. This gene variant is one that increases the risk of developing Alzheimer’s disease, the ε4 variant changes the function of APOE, leading to an accumulation of harmful proteins in the brain, which are beta-amyloid and tau. This provides an explanation as to why women are more likely to get Alzheimer’s disease, as well as why hormone therapy can help slow down this process.
Through understanding all these studies, we are able to determine that the loss of estrogen and progesterone through menopause, puts the brain of a woman at risk. The findings have shown that there is a critical window in which hormone therapy can help counteract these effects. It is most effective during the perimenopausal stage, or the 5 year period after starting menopause. These studies have shown that hormone therapy protects the brain from losing cognitive function and reduces the accumulation of harmful brain proteins like beta-amyloid and tau, which in turn lowers the risk of Alzheimer’s, especially in women carrying the APOE ε4 gene. Even though these articles have all highlighted the positive preventative properties of hormone therapy, there is much research still necessary to be done to examine and really understand the long-term effects of hormone therapy in postmenopausal women to prevent neurodegenerative diseases.
References
Ali, Noor, et al. “The Role of Estrogen Therapy as a Protective Factor for Alzheimer’s Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature.” Cureus, U.S. National Library of Medicine, 6 Aug. 2023, pmc.ncbi.nlm.nih.gov/articles/PMC10480684/.
Depypere, Herman, et al. Menopause Hormone Therapy Significantly Alters Pathophysiological Biomarkers of Alzheimer’s Disease - Depypere - 2023 - Alzheimer’s & Dementia - Wiley Online Library, alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12759.
Singh, M., Krishnamoorthy, V. R., Kim, S., Khurana, S., & LaPorte, H. M. (2024, January 15). Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection. Frontiers. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1286066/full
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