For many years, menopause has been associated with hot flashes, low libido, brain fog, and rage. But recently, research has shown significant brain changes approximately two years before to two years after the last menstrual cycle that could be contributing to these symptoms. This article will address these changes and how to support women during this transition with a root cause approach.
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3 Ways Menopause Affects The Brain
1. Hormonal Changes Influence Neurotransmitter Production
Sex hormones interact deeply with brain neurotransmitters, including serotonin, GABA, glutamate, and dopamine. (1-15) (17-20)
Estrogen: affects emotions and neurotransmitter production in many ways, including:
- Influencing serotonin levels and serotonin receptors.
- Modifying endorphin levels, the "feel-good" chemicals.
- Modulate stress by influencing the release of stress neurotransmitters, such as epinephrine and norepinephrine.
Estrogen has been reported to have a powerful serotonin-modulating effect by regulating the enzyme involved in its production (tryptophan hydroxylase), breakdown, and receptor sensitivity. The impact of estrogen on serotonin availability depends on several factors, such as the amount of estrogen present.
Estrogen may also modulate stress by influencing the release of stress neurotransmitters, such as epinephrine and norepinephrine. It is also likely that hormonal changes in the menopausal transition could impact the breakdown of stress neurotransmitters and serotonin.
Progesterone: While not discussed nearly as much as estrogen, progesterone also plays a vital role in perimenopause and mood. Allopregnanolone, a downstream progesterone metabolite, has been said to modulate GABAa (Gamma-aminobutyric acid) receptors resulting in anti-anxiety and antidepressant effects in clinical studies. (4, 13-16)
Progesterone has also been found to influence serotonin. This is through modifying the expression of serotonin-related genes and proteins.
Some preliminary evidence suggests that progesterone is also neuroprotective in the brain, which could also impact one's resilience to stress.
2. Temporary Memory & Cognitive Declines
Menopausal women can experience issues with cognition and memory as estrogen levels dip. Estrogen has special receptors that play an essential role in our brain. (2, 3) These receptors are found within the limbic region of the brain (an area that controls mood and emotion). Currently, two receptors for estrogen in the limbic region have been identified, ER-alpha (ERalpha) and ER-beta (ERbeta). ERalpha regulates reproductive neuroendocrine behavior and function. ERbeta appears to play a role in nonreproductive behaviors, such as learning and memory, anxiety, and mood. (4, 7, 11-13)
When these hormone levels shift, every system interacting with them, including your brain, registers these changes. So, it makes sense that when estrogen levels drop, as, in menopause, cognition and mental functioning can temporarily change due to all the different areas it influences in the brain. (1-5). The good news is this is usually temporary, and rebalancing estrogen levels have been shown to modulate cognitive function.
3. The Structure of The Brain Changes
The ventral limbic and medial temporal lobe brain areas can be altered in menopause. These regions influence the consolidation of negative emotional information. This is likely influenced by the presence of estrogen receptors in this area, as noted above. This impact on brain function may also cause mood changes and memory issues.
One recent study used several types of brain imaging, magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and positron emission tomography (PET), to scan the brains of 161 women between the ages of 40 and 65. Some of the women were menopausal (one year without menstruation), some were transitioning to menopause ("perimenopause"), and a third group was post-menopausal.
The results indicated various brain changes in the menopause transition. These included:
- The gray matter volume was lower in the inferior temporal gyrus, which is associated with high-level visual perception.
- Glucose use was lower in the temporal lobes (the brain area involved in memory and perception).
- White matter volume declined in multiple regions throughout the brain.
- Deposits of amyloid beta (Alzheimer's-associated protein) were higher in women who carried the ε4 variant of the APOE gene, highlighting a connection between menopause and a higher Alzheimer's risk for women.
Interestingly, the brain compensated for these changes by increasing cerebral blood flow and energy production in these areas. The researchers' analyses also suggested that some declines occurred only temporarily during the menopausal transition and were reversed at menopause or years afterward.
Functional Medicine Labs to Test for Menopausal Women
Hormonal Panel
Measuring hormones can help a practitioner narrow down where support is needed for cognition, health, and mood. Each type of hormonal test, blood, salvia, and urine, has unique advantages and disadvantages, and they are often chosen based on practitioner preference. (35-36)
A dried urine test is one of the most popular comprehensive hormone tests as it can help determine how a woman breaks down hormone metabolites and assess markers for stress and inflammatory estrogens (indicating issues in the estrobolome) that impact mood and cognition.
Neurotransmitter Test
Due to the bi-directional relationship between the brain and hormones, assessing neurotransmitters can be helpful. Narrowing down which neurotransmitters are out of balance, a practitioner can use nutrition, supplemental, and lifestyle factors to address these imbalances.
Comprehensive Stool Test
A healthy microbiome can foster a balanced mood via the gut-brain-estrogen connection. The population of gut bacterial genes capable of metabolizing estrogens is termed the "estrobolome." This process can become impaired through dysbiosis. The altered circulating estrogens can further contribute to menopause symptoms, including cognitive and mood changes. Comprehensive stool tests offer a complete look at gut health by measuring pathogens and analyzing digestion, nutrient absorption, inflammation, and immune function, all of which impact the gut-brain-estrogen axis.
What Can Women Do to Maintain Brain Health During Menopause?
Since most changes in the female brain during menopause are influenced by hormonal shifts, focusing on natural approaches to optimize hormonal balance and cognitive function is essential.
Movement
Increased oxygenation and blood flow from exercise enhance bodily support to all organ systems, including the brain. There is a wealth of information on how exercise can improve brain and cognitive health, enhance brain growth, and facilitate mental facilities. (36-41)
Generalized brain effects include a boost in the number of blood vessels and synapses, increased brain volume, and decreased age-related brain atrophy. Localized effects include growing new nerve cells and proteins to help these neurons survive and thrive. This improves thinking and problem-solving skills.
The best exercise for one person may differ for another, as we are all different. All forms of exercise have support in the literature for improving brain health. At least 150 minutes of physical activity per week, but in reality, it may be that one has to start slow and work their way up to more activity.
Nutrition
A diet rich in whole foods, high-quality protein, omega-3-rich fats, and carbohydrates (such as the Mediterranean diet) has been shown to have beneficial effects on memory function.
Including foods rich in omega-3 fatty acids or supplementing with fish oil is especially important. Research demonstrates correlations to essential fatty acids, brain development, and mood and behavior outcomes. (43-46)
Probiotic foods that support the gut-brain axis can also help. Some probiotics have been termed "psychobiotic" (47-48), which is a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness." These bacteria have been found to produce neuroactive substances, including GABA and serotonin, that can act on the gut-brain axis.
Brain Stimulating Activities
Effortful cognitive activity and social contact have beneficial effects on the brain. Social contact is another form of keeping our brains active through external stimuli, novel experiences, and perspectives outside ourselves.
Sleep
Getting proper sleep (approximately seven hours a night) is critical for brain health. It plays a crucial role in storing and maintaining memory and even helps clear the brain of the protein amyloid, one of the potential markers of potential Alzheimer's Disease (AD) pathology.
Stress Reduction
Stress influences the emotional tone and can impact hormonal balance. Studies have shown stress reduction and relaxing techniques can relieve symptoms of menopause and decrease tension, anxiety, and depression while lessening mood swings.
Aromatherapy
Aromatherapy can help with relaxation, sleep, mood, and stress. Some studies also support the role of essential oils for mood and hormonal balance. These include:
Lavender: Lavender, when combined with other oils, was also shown to improve psychological symptoms. In a double-blinded 12-week clinical crossover trial of 100 women, lavender essential oil reduced hot flash frequency by 50% compared with a <1% reduction in the placebo group.
Clary Sage: Clary sage oil has been shown to have an antidepressant-like effect. In one small trial with 22 women, clary sage oil decreased cortisol levels and increased 5-hydroxytryptamine (5-HT). It also improved depression ratings.
Geranium and Rose: In one trial, salivary estrogen concentration was elevated upon inhalation exposure to geranium and rose oil. Together with previous studies, this study supports the notion that olfactory exposure to some essential oils can influence the salivary concentration of estrogen.
Neroli (Bitter Orange): In one study with 63 healthy postmenopausal women, inhalation of neroli oil for five days for five minutes twice daily improved serum estrogen and cortisol concentrations. It also enhanced sexual desire, blood pressure, and heart rate.
Rosemary: There is some evidence that rosemary oil supports memory. For example, one study found that the aroma of rosemary essential oil could improve the ability to remember events and tasks at particular times in the future.
Herbs
Various herbs are supportive of menopausal symptoms through a variety of mechanisms and can help with mood and cognitive decline. These include:
Ashwagandha: has been shown to restore synaptic function and neural regeneration, reverse mitochondrial dysfunction and improve auditory–verbal working memory.
Ginko Biloba: Improves mitochondrial function, stimulates cerebral blood flow, blocks neural cell death, and stimulates neurogenesis.
Lion's Mane: has neuroprotective properties, improves cognition, is anti-inflammatory, blocks Aβ production, and stimulates neurotransmission and neurite outgrowth.
Turmeric has been shown to have anti-inflammatory effects, block Aβ production, and inhibit neural cell death.
St. John's Wort: has been shown to improve mild to moderate depression in the general population and appears to show efficacy for mood disorders related to the menopausal transition.
Pueraria mirifica: has been researched extensively for its beneficial effects in treating menopausal symptoms. It contains the phytoestrogen miroestrol, which functions as a selective estrogen receptor modulator (SERM). SERMs selectively bind to estrogen and block or enhance estrogen receptor stimulation. This can help with balancing hormones and mood.
Phytoestrogens: Food or herbal-based phytoestrogens are plant-derived compounds commonly sourced from soy and red clover (isoflavones)) flaxseed (lignans), and hops (Humulus lupulus). They are frequently used to reduce hot flashes in perimenopausal and menopausal women and may impact hormonal levels of estrogen, which could affect mood.
Hormone Replacement Therapy
Studies suggest that hormone supplementation has positively affected mood and cognitive functioning in domains such as working memory and executive control. The hippocampus, the brain center for memory, has also been shown to be larger in women on hormone replacement therapy.
Note: It is imperative to personalize HRT for every woman and to weigh the side effects against the benefits.
Summary
Menopause can cause many changes to the brain related to changes in hormones, neurotransmitters, memory, brain structure, and the gut-brain-estrogen axis. Thankfully, this is usually temporary, in the meantime, there are many lifestyles, dietary, and supplemental support options women can utilize to preserve cognitive and mental function.
For many years, menopause has been associated with hot flashes, low libido, brain fog, and rage. Recent research suggests there are significant brain changes approximately two years before to two years after the last menstrual cycle that may contribute to these symptoms. This article will discuss these changes and how to support women during this transition with a root cause approach.
[signup]
3 Ways Menopause May Affect The Brain
1. Hormonal Changes May Influence Neurotransmitter Production
Sex hormones interact with brain neurotransmitters, including serotonin, GABA, glutamate, and dopamine. (1-15) (17-20)
Estrogen: may affect emotions and neurotransmitter production in several ways, including:
- Influencing serotonin levels and serotonin receptors.
- Modifying endorphin levels, the "feel-good" chemicals.
- Potentially modulating stress by influencing the release of stress neurotransmitters, such as epinephrine and norepinephrine.
Estrogen has been reported to have a serotonin-modulating effect by regulating the enzyme involved in its production (tryptophan hydroxylase), breakdown, and receptor sensitivity. The impact of estrogen on serotonin availability may depend on several factors, such as the amount of estrogen present.
Estrogen may also modulate stress by influencing the release of stress neurotransmitters, such as epinephrine and norepinephrine. It is also possible that hormonal changes in the menopausal transition could impact the breakdown of stress neurotransmitters and serotonin.
Progesterone: While not discussed as much as estrogen, progesterone also plays a role in perimenopause and mood. Allopregnanolone, a downstream progesterone metabolite, has been said to modulate GABAa (Gamma-aminobutyric acid) receptors, which may result in anti-anxiety and antidepressant effects in clinical studies. (4, 13-16)
Progesterone has also been found to influence serotonin. This is through modifying the expression of serotonin-related genes and proteins.
Some preliminary evidence suggests that progesterone may be neuroprotective in the brain, which could also impact one's resilience to stress.
2. Temporary Memory & Cognitive Changes
Menopausal women may experience issues with cognition and memory as estrogen levels change. Estrogen has special receptors that play a role in our brain. (2, 3) These receptors are found within the limbic region of the brain (an area that controls mood and emotion). Currently, two receptors for estrogen in the limbic region have been identified, ER-alpha (ERalpha) and ER-beta (ERbeta). ERalpha regulates reproductive neuroendocrine behavior and function. ERbeta appears to play a role in nonreproductive behaviors, such as learning and memory, anxiety, and mood. (4, 7, 11-13)
When these hormone levels shift, every system interacting with them, including your brain, registers these changes. So, it makes sense that when estrogen levels drop, as in menopause, cognition and mental functioning can temporarily change due to all the different areas it influences in the brain. (1-5). The good news is this is usually temporary, and rebalancing estrogen levels may help modulate cognitive function.
3. The Structure of The Brain May Change
The ventral limbic and medial temporal lobe brain areas may be altered in menopause. These regions influence the consolidation of negative emotional information. This is likely influenced by the presence of estrogen receptors in this area, as noted above. This impact on brain function may also cause mood changes and memory issues.
One recent study used several types of brain imaging, magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and positron emission tomography (PET), to scan the brains of 161 women between the ages of 40 and 65. Some of the women were menopausal (one year without menstruation), some were transitioning to menopause ("perimenopause"), and a third group was post-menopausal.
The results indicated various brain changes in the menopause transition. These included:
- The gray matter volume was lower in the inferior temporal gyrus, which is associated with high-level visual perception.
- Glucose use was lower in the temporal lobes (the brain area involved in memory and perception).
- White matter volume declined in multiple regions throughout the brain.
- Deposits of amyloid beta (Alzheimer's-associated protein) were higher in women who carried the ε4 variant of the APOE gene, highlighting a potential connection between menopause and a higher Alzheimer's risk for women.
Interestingly, the brain compensated for these changes by increasing cerebral blood flow and energy production in these areas. The researchers' analyses also suggested that some declines occurred only temporarily during the menopausal transition and were reversed at menopause or years afterward.
Functional Medicine Labs to Consider for Menopausal Women
Hormonal Panel
Measuring hormones can help a practitioner identify areas where support may be needed for cognition, health, and mood. Each type of hormonal test, blood, saliva, and urine, has unique advantages and disadvantages, and they are often chosen based on practitioner preference. (35-36)
A dried urine test is one of the most popular comprehensive hormone tests as it can help determine how a woman breaks down hormone metabolites and assess markers for stress and inflammatory estrogens (indicating issues in the estrobolome) that may impact mood and cognition.
Neurotransmitter Test
Due to the bi-directional relationship between the brain and hormones, assessing neurotransmitters can be helpful. By identifying which neurotransmitters may be out of balance, a practitioner can consider nutrition, supplemental, and lifestyle factors to address these imbalances.
Comprehensive Stool Test
A healthy microbiome can support a balanced mood via the gut-brain-estrogen connection. The population of gut bacterial genes capable of metabolizing estrogens is termed the "estrobolome." This process can become impaired through dysbiosis. The altered circulating estrogens may further contribute to menopause symptoms, including cognitive and mood changes. Comprehensive stool tests offer a complete look at gut health by measuring pathogens and analyzing digestion, nutrient absorption, inflammation, and immune function, all of which may impact the gut-brain-estrogen axis.
What Can Women Consider to Support Brain Health During Menopause?
Since most changes in the female brain during menopause are influenced by hormonal shifts, focusing on natural approaches to support hormonal balance and cognitive function is essential.
Movement
Increased oxygenation and blood flow from exercise may enhance bodily support to all organ systems, including the brain. There is a wealth of information on how exercise can support brain and cognitive health, enhance brain growth, and facilitate mental facilities. (36-41)
Generalized brain effects may include a boost in the number of blood vessels and synapses, increased brain volume, and decreased age-related brain atrophy. Localized effects may include growing new nerve cells and proteins to help these neurons survive and thrive. This may improve thinking and problem-solving skills.
The best exercise for one person may differ for another, as we are all different. All forms of exercise have support in the literature for improving brain health. At least 150 minutes of physical activity per week is often suggested, but in reality, it may be that one has to start slow and work their way up to more activity.
Nutrition
A diet rich in whole foods, high-quality protein, omega-3-rich fats, and carbohydrates (such as the Mediterranean diet) has been shown to have beneficial effects on memory function.
Including foods rich in omega-3 fatty acids or supplementing with fish oil may be especially important. Research demonstrates correlations to essential fatty acids, brain development, and mood and behavior outcomes. (43-46)
Probiotic foods that support the gut-brain axis may also help. Some probiotics have been termed "psychobiotic" (47-48), which is a live organism that, when ingested in adequate amounts, may produce a health benefit in patients. These bacteria have been found to produce neuroactive substances, including GABA and serotonin, that can act on the gut-brain axis.
Brain Stimulating Activities
Effortful cognitive activity and social contact may have beneficial effects on the brain. Social contact is another form of keeping our brains active through external stimuli, novel experiences, and perspectives outside ourselves.
Sleep
Getting proper sleep (approximately seven hours a night) is important for brain health. It plays a role in storing and maintaining memory and may even help clear the brain of the protein amyloid, one of the potential markers of potential Alzheimer's Disease (AD) pathology.
Stress Reduction
Stress influences the emotional tone and can impact hormonal balance. Studies have shown stress reduction and relaxing techniques may help relieve symptoms of menopause and decrease tension, anxiety, and depression while lessening mood swings.
Aromatherapy
Aromatherapy may help with relaxation, sleep, mood, and stress. Some studies also support the role of essential oils for mood and hormonal balance. These include:
Lavender: Lavender, when combined with other oils, was also shown to improve psychological symptoms. In a double-blinded 12-week clinical crossover trial of 100 women, lavender essential oil reduced hot flash frequency by 50% compared with a <1% reduction in the placebo group.
Clary Sage: Clary sage oil has been shown to have an antidepressant-like effect. In one small trial with 22 women, clary sage oil decreased cortisol levels and increased 5-hydroxytryptamine (5-HT). It also improved depression ratings.
Geranium and Rose: In one trial, salivary estrogen concentration was elevated upon inhalation exposure to geranium and rose oil. Together with previous studies, this study supports the notion that olfactory exposure to some essential oils can influence the salivary concentration of estrogen.
Neroli (Bitter Orange): In one study with 63 healthy postmenopausal women, inhalation of neroli oil for five days for five minutes twice daily improved serum estrogen and cortisol concentrations. It also enhanced sexual desire, blood pressure, and heart rate.
Rosemary: There is some evidence that rosemary oil may support memory. For example, one study found that the aroma of rosemary essential oil could improve the ability to remember events and tasks at particular times in the future.
Herbs
Various herbs are supportive of menopausal symptoms through a variety of mechanisms and may help with mood and cognitive decline. These include:
Ashwagandha: has been shown to support synaptic function and neural regeneration, may help reverse mitochondrial dysfunction and improve auditory–verbal working memory.
Ginko Biloba: May support mitochondrial function, stimulate cerebral blood flow, block neural cell death, and stimulate neurogenesis.
Lion's Mane: has neuroprotective properties, may improve cognition, is anti-inflammatory, may block Aβ production, and stimulate neurotransmission and neurite outgrowth.
Turmeric has been shown to have anti-inflammatory effects, may block Aβ production, and inhibit neural cell death.
St. John's Wort: has been shown to improve mild to moderate depression in the general population and appears to show efficacy for mood disorders related to the menopausal transition.
Pueraria mirifica: has been researched for its potential effects in supporting menopausal symptoms. It contains the phytoestrogen miroestrol, which functions as a selective estrogen receptor modulator (SERM). SERMs selectively bind to estrogen and may block or enhance estrogen receptor stimulation. This may help with balancing hormones and mood.
Phytoestrogens: Food or herbal-based phytoestrogens are plant-derived compounds commonly sourced from soy and red clover (isoflavones)) flaxseed (lignans), and hops (Humulus lupulus). They are frequently used to reduce hot flashes in perimenopausal and menopausal women and may impact hormonal levels of estrogen, which could affect mood.
Hormone Replacement Therapy
Studies suggest that hormone supplementation may have positive effects on mood and cognitive functioning in domains such as working memory and executive control. The hippocampus, the brain center for memory, has also been shown to be larger in women on hormone replacement therapy.
Note: It is important to personalize HRT for every woman and to weigh the side effects against the benefits. Always consult with a healthcare provider before starting any new treatment.
Summary
Menopause can cause many changes to the brain related to changes in hormones, neurotransmitters, memory, brain structure, and the gut-brain-estrogen axis. Thankfully, this is usually temporary. In the meantime, there are many lifestyle, dietary, and supplemental support options women can consider to help maintain cognitive and mental function.
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