Neuroscience research has had a huge impact on how we understand the human body. Through this research, scientists have discovered many different functions of the brain, leading to new therapies and monumental discoveries about how we, as human beings, function. Scientists have also been able to develop new techniques to treat illnesses and diseases by finding out their various root causes in the brain. Unfortunately, these “root causes” and discoveries are often difficult to elucidate from person to person and differ in varying populations. One large gap in knowledge in the biomedical research industry is a lack of research on women.
Women have historically been excluded from many research projects, specifically involving neuroscience, due to fluctuating hormone levels. This has led to an enormous gap in knowledge on how to treat and cater care to women (Martin, 2022). Recently, research has finally begun in regard to key hormones that may have a large impact on the brain, and how fluctuating levels of these hormones during menstruation, pregnancy, and menopause can influence brain functioning (Martin, 2022)
Progesterone (P4) is one hormone prevalent in women that plays an essential part in stroke recovery (Nguyen et al., 2018). P4 activates various learning and memory pathways by increasing brain-derived neurotrophic factor (BDNF) levels. BDNF has been shown to aid neuronal growth by helping neurons form new synaptic connections and increasing cross-talk between neurons. BDNF is extremely important in stroke recovery as it helps neurons form connections to ameliorate neuronal damage (Nguyen et al., 2018). P4 has also been shown to fluctuate in women whether it is during the menstrual cycle or because women are taking some form of birth control.
Another hormone that has been central to female development was discovered to play a similar role as P4 in the brain. Estrogen has also been found to protect neurons through increasing levels of BDNF. Going further, researchers modeled an environment similar to menopause in mice to study estrogen and its effects on learning and memory. Researchers studied mice without ovaries (no estrogen production), mice with ovaries, and mice without ovaries but with hormone supplements (Nguyen et al., 2018). When these mice were tested for their learning capabilities, mice without ovaries did significantly worse than mice with ovaries and mice with hormone supplements. This research has devastating implications for women going through menopause and forgoing hormone therapy. While great headway is being made in investigating how hormones like P4 and estrogen impact the brain in mice, it is time to study these hormones in the human brain.
Frustrated with a lack of information regarding women’s brains, a new study, 28 and me, began to accumulate data on hormonal changes occurring during a woman’s menstrual cycle and how those changes relate to the brain. In this study, women’s brains were imaged using fMRI each day for 28 days (Martin, 2022). Results found that when estrogen levels peaked during ovulation in the menstrual cycle, networks in the brain, specifically the default mode network, became more active and increased connections. The default network, while still being researched, is a network in the brain thought to contribute to remembering, daydreaming, and thinking about the future. When P4 levels increased after ovulation, gray matter structures tied to learning and memory expanded. Interestingly, when one of the women returned to the study after being on birth control for a year, which reduces P4 levels, the increases in gray matter were not observed throughout the 28 days. Clearly, the brain is largely influenced by fluctuating hormone levels. So what implications could this have on the impacts of menopause and hormonal shifts during menstrual cycles that were not previously studied?
One large impact that is yet to be explored is the way menopause can change the brain’s structure through hormones, or lack thereof, as foreshadowed by the previous study. As with the mice, in women who have gone through menopause and have decreased levels of estrogen, there tends to be a propensity for forgetfulness and an inability to concentrate (Russell et al., 2019). Decreased estrogen levels also lead to various mood disorders and increased sleep issues. In fact, lowered levels of estrogen are related to Alzheimer’s disease, schizophrenia, and depression. Furthermore, when looking at the effects of menopause on a smaller neuronal layer, lower estrogen levels are related to “reduced dendritic spines, decreased synaptic density, decreased numbers of specific synapses…changes in connectivity…” (Russell et al., 2019).
Treatment for menopause that may immediately come to mind includes increasing the amount of estrogen circulating in the body, or hormone therapy. Similar to what the hypothesis would be, groups of women post-menopause that took artificial estrogen have seen benefits including increases in synaptic density in select areas of the brain. However, there is a certain window of opportunity that must be taken into account when using hormone therapy as a treatment. When that window of time to treat women has passed, hormone therapy will have little to no effect. This is especially true in women who may develop Alzheimer's in part due to a lack of estrogen or P4, as hormone therapy will not be an effective treatment after Alzheimer’s has already taken root in the brain.
Overall, additional research is still needed to elucidate the long-term effects of hormone therapy, birth control, menopause, and the menstrual cycle on the brain. It is also crucial to inform women of the power of hormone therapy and the risks of not having enough natural hormones circulating in one’s body. Additionally, it is essential to begin studies across various populations including women, to help make new and effective treatments for tragic diseases such as Alzheimer’s that are linked to hormones such as P4 and estrogen. Fortunately, with hormone therapies now starting to become possible treatments for disorders like depression and Alzheimer’s, women are finally getting the care they deserve from the neuroscience community.
Works Cited
Martin, Cassie. “Emily Jacobs Wants to Know How Sex Hormones Sculpt the Brain.” Science News, September 29, 2022. https://www.sciencenews.org/article/emily-jacobs-female-brain-sn-10-scientists-to-watch.
Nguyen, Trinh, Chang Su, and Meharvan Singh. “Let-7i Inhibition Enhances Progesterone-Induced Functional Recovery in a Mouse Model of Ischemia.” Proceedings of the National Academy of Sciences of the United States of America 115, no. 41 (October 9, 2018): E9668–77. https://doi.org/10.1073/pnas.1803384115.
Russell, Jason K., Carrie K. Jones, and Paul A. Newhouse. “The Role of Estrogen in Brain and Cognitive Aging.” Neurotherapeutics 16, no. 3 (July 2019): 649–65. https://doi.org/10.1007/s13311-019-00766-9.
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