This month, we sat down with Caroline Just, MD, a neurologist in the Cleveland Clinic Center for General Neurology, and Pelin Batur, MD, a women’s health specialist in the Department of Subspecialty Care for Women’s Health. Together we explore the intricate connection between hormonal changes during menopause and cognitive health. As millions of women navigate the complex transition of menopause, many experience cognitive symptoms like “brain fog” that can impact daily functioning. Through their complementary expertise, this month’s experts offer valuable insights for women seeking to understand and address cognitive concerns during perimenopause and beyond.
Read the Q&A with Dr. Just and Dr. Batur below.
WAM: Could you explain how estrogen affects brain function and why the drop in hormones during menopause might impact cognitive health?
Dr. Just: It is thought that estrogen increases the brain’s ability to form new connections, increases the number of receivers (dendrites) on each brain cell, and promotes growth of new cells in the memory storage structure of the brain, which is called the hippocampus. Estrogen also reduces neuroinflammation and reduces amyloid protein buildup in brain tissues. When estrogen levels drop in the setting of menopause, we lose all of these protective functions of estrogen. In animal models, estrogen deficiency has associated with increased breakdown in the hippocampus.
WAM: Some women experience brain fog during perimenopause and menopause. What’s happening hormonally during these times, and what can women do to support their cognitive function?
Dr. Just: The current theory is that reduction in estrogen levels is the reason for these symptoms of brain fog. Women experience this as reduced memory, slowed thinking, and trouble focusing. It is helpful to optimize your brain function in every other way: good quality sleep, a balanced diet such as the Mediterranean, and regular exercise, targeting 150 minutes per week of moderate intensity aerobic activity and some load-bearing exercises like light weight training.
Dr. Batur: It is important to remember that there are multiple contributors to brain fog, not just declining levels of estrogen. In fact, during perimenopause, women can see very high levels of estrogen due to an additional episode of ovulation occurring earlier than expected (called luteal out of phase, or LOOP events). The LOOP events occurring during perimenopause can cause estrogen levels much higher than seen during a normal menstrual cycle. Also, many women describe brain fog symptoms when they’re having very little menopausal symptoms and continue to have normal menstrual bleeding, well before their perimenopausal years. Our busy lives and being exposed to too many stressors, including not being in the moment and needing to multitask, can all potentially contribute to the brain fog/cognitive symptoms. Women in this phase of life are often caring for younger generations, caring for older generations, at the peak of their careers, and managing physical changes to not just their own bodies, but also supporting their partners’ health concerns. Sometimes the burden of these responsibilities keeps us up at night, overwhelmed with to do lists, or makes us predisposed towards depression and anxiety. All of these factors diminish our brain and body’s energy reserves and contribute to a variety of symptoms that we collectively call brain fog.
WAM: There is research that suggests hormone therapy might help protect cognitive function during the menopause transition. What’s the latest evidence on hormone therapy and brain health and on whether there might be a connection between a woman’s journey through menopause and her risk for developing Alzheimer’s disease later in life?
Dr. Just: There is evidence to suggest estrogen therapy in perimenopause and menopause may do the helpful jobs that estrogen does pre-menopause, such as promote connection formation and reduce inflammatory protein. We are actively studying the connection between brain fog in menopause and risk of subsequent Alzheimer’s disease.
Dr. Batur: Despite the benefits that Dr. Just and I are discussing, we have strong science that tells us that initiation of hormones in the mid 60s and beyond can increase dementia risks. Both national and international expert guideline recommendations discourage using hormones for the purposes of preventing dementia, including for those who are in their 40s and 50s of age. The reason for this conservative recommendation is that we don’t have convincing and consistent evidence to show that hormones can prevent dementia, and we want to also be mindful of the potential risks of long-term hormone use. This is an area that needs much more research to understand who would best benefit from hormone therapy, when to initiate treatment, and for how long to use it. We need the science to answer what is best for overall brain health, considering not only the risks of dementia, but also the risks of stroke, and how treatment may impact our longevity (how long we will live).
WAM: We know stress affects hormones and brain function. How exactly does chronic stress impact our hormonal balance, and what are the potential long-term effects on cognitive health?
Dr. Just: Our hormonal response to stress is managed by our hypothalamus, pituitary, and adrenal glands. This system uses sensitive feedback loops to ensure we can respond to stress when we need to and can rest and heal when we need to. When we experience chronic stress, our cortisol levels no longer respond to the same feedback loops. It is thought that this dysregulation of cortisol levels worsens neurodegenerative diseases like Alzheimer’s Disease.
Dr. Batur: It is important to remember that during this phase of life there are other hormonal systems that may be impacted by stress, including an increased risk of thyroid disease. Additionally, we frequently uncover individuals who assumed that their symptoms are due to stress or hormonal fluctuations, when in fact they have very low B12 levels. So, it is important to take a step back and look at the entire person as a whole, including any other potential contributors to their symptoms.
WAM: How might emerging research on hormones, menopause, and brain health change how we approach women’s cognitive health in the future?
Dr. Just: In the future we may be able to predict which patients are most likely to benefit from hormone therapy through genetic testing even before they begin showing symptoms. There is also ongoing research to understand vasomotor symptoms, such as hot flashes, and whether experiencing these has any relationship to cognitive health.
Dr. Batur: Many menopause specialists believe in the concept of the “timing hypothesis”, also called the “window of opportunity”. This suggests that hormone therapy has different impacts on heart and brain depending on how healthy the arteries are when treatment is initiated. An emerging focus on understanding cardiovascular risks in women, including additional testing such as coronary artery calcification to detect early atherosclerosis, will be critical to better assess an individual woman’s risks of not only cardiovascular and brain diseases, but also the net benefits versus risks of hormonal treatment options.