October is Menopause Awareness month with the 18th of October recognized as World Menopause Day.
After so many years of neglect and gaslighting, women are finally seeing unprecedented attention given to Menopause; with greater empowerment over the care for their menopausal symptoms. One such polarizing treatment is, of course, Menopause Hormone Therapy (MHT; also known as Hormone Replacement Therapy). ( I won’t get into the full history of the pendulum swings of MHT prescriptions; but for those that are interested on the upswing until the Women’s Health Initiative and the misinterpretation of the study by the media, then the fear around the data, to the current popular media push for every menstruating individual to use MHT as a powerful anti-aging agent.)
Before I get a blaze of DMs and emails - I am NOT anti-MHT, but I am anti-rhetoric that hormone therapy is the be-all, end-all panacea that is being pushed around with misinformation. There are many alternatives to use that do not involve hormones and should also be considered.
This past September saw Chicago host the annual Menopause Society meeting. At the conference, scientists broke down the latest research on a broad range of topics, from brain and bone health to managing sleep, substance use, and workplace challenges during the menopause transition; with the primary goal of educating and reducing the misinformation flow that is currently rampant across many platforms. The current guidelines are quite clear on what has data to support the use of hormone therapy, and what does not; and what research is being done to further the understanding of symptoms, health outcomes of treatment, longevity, and who benefits from using MHT vs other therapies.
The one belief that menopause hormone therapy prevents dementia and Alzheimer’s was challenged and it is crystal clear that currently there is NO EVIDENCE to support the use of MHT for cognition or for the prevention of dementia. Conflicting, observational evidence exists around the use of MHT for Alzheimer’s, but we see the limited evidence for the use is beneficial for women who are carriers of the APOE4 gene (genetically have a higher risk of developing Alzheimer’s disease, but this does not mean that they will!). I also want to point out that MHT is a tool in the toolbox and should definitely be considered if you are experiencing symptoms that warrant its use. I will repeat- I am NOT anti-MHT, but I am anti-rhetoric that hormone therapy is the be-all, end-all panacea that is being pushed around with misinformation. There are many alternatives to use that do not involve hormones and should also be considered.
More to the point, not everyone can or wants to use MHT, yet there is so much rhetoric and fearmongering that if they don’t, they have a high risk of developing cognitive disorders and cardiovascular disease. I want to bring to light, as an exercise physiologist, the use of exercise as a tried-and-true treatment for brain and cardiovascular health. I am not talking about 150 minutes of moderate intensity exercise with 2x week muscle strengthening exercise as prescribed by the general health authorities (caveat- if you do not move at all, yes, of course start by moving! But for most, if not all, of you reading this, are already highly active and are part of the very under-studied woman who ascribes to the fitness and health lifestyle!). I am talking about specific intensities and duration of aerobic, anaerobic, and resistance training modes of exercise.
Let’s review! I have already discussed the benefits of HIIT (including SIT) on body composition and metabolic health in peri/post-menopausal women; and I have also discussed the AHA’s new position on resistance training for skeletal muscle and cardiovascular health; now let’s look a bit closer on brain health and Alzheimer’s prevention.
Part 1: The Landscape of cognitive decline and Alzheimer's Disease (AD)
Most women will tell you that with perimenopause comes thinking, concentration, and memory issues, but when these impairments don’t abate after perimenopause, it may be Mild Cognitive Impairment (MCI). MCI is a small but noticeable decline in memory or thinking skills which affects ~15-20% of individuals over the age of 65 and is clinically thought to be the state between normal cognition and dementia. Dementia (Alzheimer’s disease is a form of dementia) is typically diagnosed when MCI has become severe enough to compromise social and/or occupational functioning. Alzheimer’s disease is a progressive neurodegenerative disorder characterized by the deterioration of cognitive functions, including memory, language, and problem-solving abilities. As the disease advances, individuals may struggle with daily activities, experience significant personality changes, and ultimately face loss of independence1. According to the Alzheimer’s Association, nearly two-thirds of individuals with Alzheimer’s are women2. This disparity raises critical questions about the underlying factors contributing to the increased risk in women, especially during the pivotal life transition of menopause.
Women and Alzheimer's Disease Risk
Two of the key factors contributing to the heightened risk of Alzheimer’s disease in women are the hormonal and metabolic changes that occur during menopause, thought to be driven by the changes in circulating estradiol. (I will point out, however, that changes in brain structure and function are not restricted to peri-post menopause. We see structural changes across all hormonal transitions: puberty, menstrual cycle, oral contraceptives and other hormonal therapies, pregnancy, as well as peri-post menopause).
Estradiol (E2) supports neuronal growth, reduces inflammation, and protects against cell death through several mechanisms. E2 enhances brain glucose metabolism (glucose is key for brain function), promotes synaptic plasticity, the brain's ability to adapt and form new connections based on experiences, and influences neurotransmitter systems and helps regulate blood flow to the brain, further supporting cognitive health.
With peri into post-menopause and the dramatic shift to very low circulating estradiol, we see three key factors affecting brain health and increasing the risk for cognitive decline:
- Increased Hypometabolism: Hypometabolism refers to reduced energy production in the brain. In menopause, many women experience significant drops in glucose metabolism in critical brain areas, particularly the hippocampus, which is essential for memory formation. Additionally, there is an increase in oxidative stress and inflammation, coupled with reduced vascular compliance and cerebral blood flow; all attributable to the precipitous drop in estradiol-related protective effects. Many women experience this more acutely after menopause, negatively impacting cognitive abilities.
- Diminished Brain Volume and Functional Connectivity: The brain may undergo atrophy or shrinkage more rapidly in late peri and early post-menopausal women. Research indicates that post-menopausal women exhibit greater surface area and volume changes of the hippocampus and changes in functional connectivity across the amygdala; associated with declines in learning, memory, and verbal tasks.
- Higher Amyloid-Beta Accumulation: Amyloid-beta is a protein that can aggregate to form plaques in the brain, a hallmark of Alzheimer’s disease. Women are more prone to accumulating these plaques, especially those carrying the APOE-ε4 allele, a genetic risk factor for AD. Women who carry the APOE-ε4 allele tend to show signs of amyloid-beta accumulation earlier than men. This genetic vulnerability, combined with hormonal changes, places women at a heightened risk for developing Alzheimer’s but does not mean she is destined to develop it!
It all sounds pretty dire, doesn’t it? Don’t freak out yet, remember this research has been done on the “normal” population, which is the generally sedentary, unfit population. When we dig into the exercise literature, we see that regular high-intensity exercise, such as high-intensity interval training (HIIT) and heavy resistance training, offers numerous benefits for brain health, particularly when looking at countering those three main issues that occur with the drop in estradiol.
In Part 2, I will highlight the benefits of HIIT, and RT, tried and true methods for attenuating cognitive decline and AD risk (and yes, cardiovascular risk too!).
