What causes postmenopausal brain fog? How can you treat and ultimately beat postmenopausal brain fog? These are a few of the top search queries on the internet? You, like many women, may be concerned about the symptoms you are noticing. You don’t need scientific studies to show that fluctuating estrogen levels causes symptoms such as weight gain, difficulty sleeping, mood changes, and the dreaded hot flashes.

You may be aware that hormone replacement therapy has gone in and out of favor. There are known risks and benefits in replacing female sex hormones, just as there are known risks and benefits of taking any prescription medication or over-the-counter supplement. There are also known risks and benefits of not replacing female sex hormones. The information can be summed up in one word, confusing!

The FDA Approved Uses For Hormone Replacement Therapy

The U.S. Food and Drug Administration has approved hormone replacement therapy for the following indications:

• Hot flashes and vasomotor symptoms: Studies have shown that oral, transdermal, or vaginal hormone replacement therapy reduces the risk of hot flashes by 65-90 percent (Bacon, 2018).
• Osteoporosis and reduction of bone fractures: A meta-analysis of 22 randomized clinical trials showed a significant reduction in nonvertebral fractures in women who began hormone therapy before age 60 and a possible decreased benefit after that (Bacon, 2018).
• Prevention of bone loss: The Women’s Health Initiative study found a significant decrease in fracture risk after women started estrogen therapy (Anderson et al. 2004).
• Brain fog and mood disorders: Treatment of menopausal symptoms, cognition and mood, and heart disease in women with premature ovarian failure, hypogonadism, or early surgical menopause all are FDA-approved uses of hormone therapy.
• Treatment of genitourinary symptoms and vaginal atrophy: Vaginal creams and suppositories are used to treat vaginal atrophy and urinary symptoms associated with menopause.

These indications cover a wide range of symptoms and provide a lot of treatment latitude.

A Woman’s Experience

Have you ever had the experience of walking into a room and forgetting why you were there? Postmenopausal brain fog is more than just inconvenient and an irritant. It can also adversely affect your career and long-term earnings potential. After menopause, estrogen levels decrease and have a myriad of effects on overall health. Postmenopausal brain fog can impact a woman’s career, her earnings potential, and ultimately her retirement account funds.

Menopause is the natural cessation of menstrual periods. It is defined as a woman who has not had her period for 12 consecutive months without another explanation. The median age of menopause is 52 years (NIH, 2005).

Menopause usually occurs between the ages of 40 and 58. In 1990, 471 million women were at least aged 50 years or older. In 2015, this number increased by 82.6% worldwide, equivalent to a 2.4% increase per year (United Nations, 2017). Average life expectancy is also increasing. Therefore, many women will spend up to 40 percent of their lives post-menopause. Women are post-menopause when they are in the highest-earning stage of their careers, considering retirement, or even pursuing a second career. For many reasons, it is essential to understand what causes postmenopausal brain fog and how you can treat and beat postmenopausal brain fog.

Brain Fog Is Memory Impairment

The ability to acquire and use knowledge is called cognition. Most women do not give this process much thought until they have difficulties with it. Imagine this. You have worked hard throughout your career and reached your career goal of senior vice president of marketing. You meet with your team biweekly. Of course, the meetings are by Zoom nowadays. You have never had to write down your agenda or take notes during your work sessions, but you have noticed yourself carrying a notepad with you everywhere.

Your first stop is your doctor’s office. You have a thorough physical exam, cognitive testing, and lab work. Everything is normal. Good news, right? You are completely healthy, but that does not explain the symptoms you are having:

• Trouble paying attention
• Difficulty concentrating
• Word-finding problems
• Taking longer to make a decision or solve a problem

It is a relief that you do not meet the criteria for dementia, and any fears that you may have had that your symptoms indicate early Alzheimer’s disease have been allayed. However, you are still uncomfortable with the knowledge that your brain function has changed. Though the change may be subtle, it is affecting your job performance. It may be due to menopause, a natural process, but it impacts your relationships and career, and you are hoping there is a solution to treat and ultimately beat postmenopausal brain fog.

What Causes Postmenopausal Brain Fog?

The sex hormones—estrogen, progesterone, and testosterone—are intimately involved with brain function. These hormones bind to receptors on nerve cells (neurons) and supporting cells (glial) in the brain. Sex hormones affect the release of chemicals in the brain called neurotransmitters. They decrease inflammation, increase blood flow to the brain, and increase connections between nerve cells.

Sex hormones influence networks of nerves that are involved in attention, memory, and other cognitive functions. Estrogen specifically affects two key areas in the brain called the hippocampus and the prefrontal cortex. These are two key areas of the brain whose focus is learning, memory, and higher-order cognitive functions (NAMI, 2019).

Perimenopause is associated with a decrease in estradiol, estrone, and progesterone and an increase in follicle-stimulating hormone. These hormonal changes are most marked during the two years before and after the final menstrual period. Studies have suggested that decreasing estrogen levels are associated with a decline in cognitive function and an increased risk for depression (Weber et al., 2014). In another study that followed 2,362 women through menopause, women noted that their cognitive function rebounded back to premenopause levels, which suggests that brain fog may be a time-limited process (Greendale et al., 2009).

The Scientific Evidence for Postmenopausal Brain Fog

Three longitudinal studies, The Study of Women’s Health Across the Nation (SWAN), The Seattle Midlife Women’s Health Study, and the Penn Ovarian Aging Study, have examined the changes in a woman’s brain function as she crosses from premenopause through menopause into post-menopause. These studies showed that the decline in memory, attention, word-finding, and other cognitive difficulties could not be attributed to age, depression, anxiety, vasomotor symptoms, or sleep disturbances (Greendale et al., 2010).

The Seattle Midlife Women’s Health Study (SMWHS) explored the types of memory changes women noticed around menopause. In this study, 508 women were enrolled and followed from 1990 until 2013. Criteria to participate included age, having at least one menstrual cycle in the past 12 months, and having an intact uterus and at least one ovary. Women were studied up to five years post-menopause.

Some findings:

• Approximately 72% of women reported problems remembering names, at least sometimes.
• About 50% had difficulty remembering where they put things, recent phone numbers, what someone had recently told them, or what they had told someone else. They also reported difficulty keeping up with a conversation, or forgetting what they were doing.
• Women also noted problems remembering words and numbers (Woods, 2016).

Weber et al. (2014) synthesized the information from multiple studies. Here are some of their findings:

• Working Memory: There was a trend for perimenopausal women to perform worse than premenopausal women, but the results were not statistically significant.
• Executive Functions: Processing speed and verbal fluency were tested. Postmenopausal women performed significantly worse than perimenopausal women on verbal fluency tasks.
• Verbal Memory: There was a trend for women to perform worse on verbal episodic memory skills, but it did not reach statistical significance. The differences in verbal memory were found to be a failure to improve over repeated administration of the same task rather than a decline in performance (Weber, Rubin & Maki, 2013).  
• Depressive Episodes: The odds of experiencing a depressive episode increased two times in perimenopause compared to premenopause.

The authors concluded that women in perimenopause and post-menopause are more likely to have delayed verbal memory than women in premenopause and an increased risk for depression.

The factors that lead to the cognitive decline associated with menopause are not completely clear. However, fluctuations in hormone levels and symptoms classically associated with menopause, such as depression, sleep disturbances, and hot flashes, may contribute by acting together or independently. (Weber, Rubin & Maki, 2013).

How to Treat Postmenopausal Brain Fog

Lifestyle Choices and Brain Fog

Lifestyle choices can help support memory function. The following may benefit memory function:

• Maintaining an extensive social network
• Remaining physically and mentally active
• Increasing omega-3 fatty acids in your diet
• Following a Mediterranean diet
• Not smoking
• Consuming alcohol only in moderation
• Reducing your risk for high blood pressure, diabetes mellitus, and high cholesterol

These lifestyle choices probably have their positive effect on memory function by supporting good overall health.

The Association Between Female Sex hormones and Brain Function

The evidence is increasing that changes in female sex hormones associated with pregnancy lead to a noticeable shift in cognitive function. Dr. Rhonda Voskuhl, a UCLA neurologist, has researched the cognitive changes seen in women with multiple sclerosis and their notable improvement during pregnancy. She used this information to develop a patented treatment using Estriol, a female sex hormone for treating women living with multiple sclerosis.

In a clinical trial, 158 women with relapsing-remitting M.S., a type of M.S. in which symptoms flare-up and then resolve, were enrolled in a clinical trial. One group was given standard therapy with Copaxone and a placebo pill. The other group received Copaxone with an 8-milligram estriol pill daily. After 12 months of treatment, the Copaxone-plus estriol group’s relapse rate was 47 percent lower than the control group. Since estriol, a female sex hormone produced during pregnancy, seems to improve the cognition of women living with multiple sclerosis. Can it also improve cognition in postmenopausal women who are experiencing brain fog, a time of known decrease in female sex hormones?

Hormone replacement therapy is FDA approved for treating women with premature or early menopause until the average age of menopause. It is also approved to treat some postmenopausal symptoms.

Hormone replacement therapy can

• Prevent osteoporosis and reduce the risk of fractures.
• Reduce the incidence of persistent hot flashes,
• Prevent bone loss
• Improve the overall quality of life

Clinical evidence has shown a low absolute risk and a favorable risk versus benefits profile for prescription hormone therapy when women experience hot flashes, night sweats, and sleep disturbances, and for osteoporosis prevention in women at increased risk (Bacon, 2018). Hormone replacement therapy has shown its value in treating many of the symptoms of menopause. Clinical trials exploring its use and benefit in decreasing the brain fog many women experience around menopause would be welcome.

The Female Sex Hormones

Estriol is a female sex hormone, along with estrone and estradiol. Estradiol is the most biologically active of the three sex hormones, estrone is 50 to 70 percent less active, and estriol, which is produced during pregnancy, is only 10 percent as active as estradiol. Among the human estrogens, only 17β-estradiol is available in a government-approved, single-estrogen product (NAMS, 2019, p285). There are multiple combination products available, including oral, transdermal, injectable, and vaginal formulations. Preparations include patches, gels, sprays, and lotions, and vaginal suppositories, creams, and rings.

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Two types of estrogen receptors are found throughout the body. Estrogen receptor alpha (ERα) is primarily in the endometrium, breast tissue, and ovaries. Whereas, Estrogen receptor beta (ERβ) is in other parts of the body such as the brain, heart, kidneys, bones, and lungs. The locations can overlap.

Initially, estriol was banned from development as a prescription or supplement without an investigational new drug application for its use. The FDA has since indicated that drug products containing estriol could be compounded in accordance with section 503A by a licensed pharmacist for a patient with a prescription. Several organizations, including the North American Menopause Society, FDA, and the American College of Obstetricians and Gynecologists, state that the benefits and risks of compounded bioidentical hormone therapies are not different from their government-approved counterparts (NAMS, 2019, 305). A claim that was previously made.

The Debate over Hormone Replacement Therapy

Concerns about using female sex-hormones after menopause are based on estrogen’s stimulatory effect on the breast and uterus. This effect can increase the risk of breast and endometrial cancer and endometrial hyperplasia. Endometrial hyperplasia is an increase in the number of cells lining the uterus. Endometrial hyperplasia is not cancer, but in some women, it may increase the risk of uterine cancer. The risk for endometrial cancer is increased when estrogen is taken unopposed or without also taking progesterone.

The risks and benefits of estrogen supplementation have been widely debated for years. All estrogens can increase the risk for heart attacks, strokes, pulmonary emboli, and deep venous blood clots in susceptible women 50 to 79 years old. Early studies on hormone replacement therapy showed promising results for decreasing osteoporosis, coronary artery disease, and mortality. Later studies conducted by the Women’s Health Initiative concluded that the risk of hormone replacement therapy was greater than the benefits. More recent studies have swung the pendulum back the other way. These studies indicate that starting hormone replacement therapy early in menopause improves quality of life and decreases osteoporosis and heart disease risk (Delgado, Lopez-Ojeda, 2020).

Prescription Therapies to Treat Menopausal Brain Fog

What is estriol’s role in potentially treating postmenopausal brain fog? Studies on the effect of hormone replacement therapy to improve the symptoms of postmenopausal brain fog are mixed. Overall, when estrogen replacement therapy was started in early menopause, benefits were noted (Sherwin, 1988). Whereas women who were started on estrogen replacement therapy after the age of 65 did not notice an improvement in cognition or memory. In fact, supplementing with estrogen well after menopause may even be detrimental to cognitive function (Shumaker et al., 2003). The type of estrogen hormone used, dosage, and whether it was combined with other hormones may be important when interpreting these studies.

Estriol is a female hormone excreted in the urine by pregnant women. Estriol is not approved for use by the FDA or Health Canada. It is available in the U.S. by prescription to be filled at a compounding pharmacy. Estriol has been approved and marketed throughout Europe and Asia for approximately 40 years to treat postmenopausal hot flashes.

Many websites offer saliva tests for women to determine their estrogen needs, followed up with the offer to compound preparations individually. The American College of Obstetricians and Gynecologists (ACOG) states there is no evidence that tests to monitor hormonal levels in saliva are biologically meaningful.

DISCLAIMER

While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice. 

References:

1. United Nations. Population Division. Department of Economic and Social Affairs. World Population Prospects: The 2017 Revision. File POP/15-3: Annual female population by five-year age group, region, subregion, and country, 1950-2100 (thousands). Estimates, 1950- 2015. June 2017. https://esa.un.org/unpd/wpp/Download/Standard/ Population/
2. Woods, N.F., Mitchell, E.S. The Seattle Midlife Women’s Health Study: a longitudinal prospective study of women during the menopausal transition and early postmenopause. womens midlife health 2, 6 (2016). https://doi.org/10.1186/s40695-016-0019-x
3. Weber, M. T., Maki, P. M., & McDermott, M. P. (2014). Cognition and mood in perimenopause: a systematic review and meta-analysis. The Journal of steroid biochemistry and molecular biology, 142, 90–98. https://doi.org/10.1016/j.jsbmb.2013.06.001
4. Greendale, G. A., Wight, R. G., Huang, M. H., Avis, N., Gold, E. B., Joffe, H., Seeman, T., Vuge, M., & Karlamangla, A. S. (2010). Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. American Journal of epidemiology, 171(11), 1214–1224. https://doi.org/10.1093/aje/kwq067
5. Weber, M. T., Rubin, L. H., & Maki, P. M. (2013). Cognition in perimenopause: the effect of transition stage. Menopause (New York, N.Y.), 20(5), 511–517. https://doi.org/10.1097/gme.0b013e31827655e5
6. The North American Menopause Society (NAMS). Crandall, C. [Ed].  (2019). Menopause Practice. A Clinician’s Guide 6^th Edition. https://www.menopause.org
7. Delgado BJ, Lopez-Ojeda W. Estrogen. [Updated 2020 Aug 24]. In: StatPearls [Internet]. Treasure Island (F.L.): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538260/
8. Bacon, J. (2018). Estrogen Therapy. Retrieved from https://emedicine.medscape.com/article/276107-overview#a9
9. National Institutes of Health. State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005 Jun 21. 142(12 Pt 1):1003-13. https://pubmed.ncbi.nlm.nih.gov/17308548/
10. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003 May 28. 289 (20):2651-62. https://pubmed.ncbi.nlm.nih.gov/12771112/
11. Sherwin BB. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology. 1988. 13 (4):345-57. https://psycnet.apa.org/record/1989-20012-001
12. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004 Apr 14. 291(14):1701-12. https://jamanetwork.com/journals/jama/fullarticle/198540
13. Greendale, G. A., Huang, M. H., Wight, R. G., Seeman, T., Luetters, C., Avis, N. E., Johnston, J., & Karlamangla, A. S. (2009). Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology, 72(21), 1850–1857. https://doi.org/10.1212/WNL.0b013e3181a71193

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