Postmenopausal confusion, also commonly referred to as postmenopausal brain fog, is a group of symptoms of

menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

in which women report problems with

cognition Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

at a higher frequency during postmenopause than before. Multiple studies on

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

performance following menopause have reported noticeable declines of greater than 60%. The common issues presented included impairments in reaction time and attention, difficulty recalling numbers or words, and forgetting reasons for involvement in certain behaviors. Association between subjective cognitive complaints and objective measures of performance show a significant impact on health-related quality of life for postmenopausal women. Treatment primarily involves symptom management through non-pharmacological treatment strategies. This includes involvement in

physical activity Physical activity is defined as any voluntary bodily movement produced by skeletal muscles that requires energy expenditure.Global Recommendations on Physical Activity for Health, 2009. World Health Organization. Geneva, Switzerland. Accessed 13/ ...

and following medically supervised diets, especially those that contain

phytoestrogen A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...

s or

resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources ...

. Pharmacological interventions in treating postmenopausal confusion are currently being researched.

Hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

is currently not indicated for the treatment of postmenopausal confusion due to inefficacy. The use of hormone replacement therapy for approved indications has identified no significant negative effect on postmenopausal cognition. Although much of the literature references women, it is important to understand that all people who undergo menopause, including those who do not self-identify as women, may experience symptoms of postmenopausal confusion.

History

Research on menopause as a whole declined with the end of the

Women's Health Initiative The Women's Health Initiative (WHI) was a series of clinical studies initiated by the U.S. National Institutes of Health (NIH) in 1991, to address major health issues causing morbidity and mortality in postmenopausal women. It consisted of three ...

(WHI) studies, but research on the treatment of symptoms associated with menopause—especially the treatment of cognitive decline—continues. The Study of Women's Health Across the Nation (SWAN), first started in 1996, continues to publish progress reports which include cognitive symptoms associated with menopausal transition, including those in postmenopause. As of 2019, SWAN indicated, "Approximately 60% of midlife women report problems with memory during the enopause transition yet studies of measured cognitive performance during the transition are rare." Although there are many relationships between hormone levels in postmenopause and cognitive function, the previously favored hormone replacement therapies (

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

therapies) have been shown to be ineffective in specifically treating postmenopausal confusion. The use of hormone replacement therapies, once considered detrimental to cognition in postmenopausal women, has now been shown to have no negative effect when used properly for approved indications. There are no conclusive studies to support any pharmacological agents, but several potential drug candidates are still being explored.

Presentation

Menopause is a natural decline in the

ovarian The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body ...

function of women who reach the age between 45 and 54 years. "About 25 million women pass through menopause worldwide each year, and it has been estimated that, by the year 2030, the world population of menopausal and postmenopausal women will be 1.2 billion, with 47 million new entrants each year." Postmenopause begins immediately following menopause (one year after the final

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

). Postmenopausal confusion is often manifested through the following cognitive symptoms: memory problems,

forgetfulness Forgetting or disremembering is the apparent loss or modification of information already encoded and stored in an individual's short or long-term memory. It is a spontaneous or gradual process in which old memories are unable to be recalled from ...

, and poor concentration.

Confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

which is otherwise unexplained and coincides with the onset of postmenopause may be postmenopausal confusion.

Causes

Risk factors

Hypertension

A 2019 literature review identified

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

and a history of

preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...

as significant risk factors for the accelerated decline of cognitive function in women during midlife. Although the mechanism remains unclear, neuroimaging studies included in the review have revealed that those with hypertension have evident structural changes in their brains. Specifically,

gray matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...

brain volume decreased and

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution ...

hyperintensity volume increased.

Atherosclerosis and comorbidities

Atherosclerosis and comorbidities such as

hyperlipidemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...

and

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

have long been considered risk factors for cognitive decline because they have the propensity to cause the formation of amyloid plaques, aggregates of misfolded, deleterious proteins, in the brain.

Insomnia

Many postmenopausal women complain of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

. Studies have shown "associations between poor sleep quality and cognitive decline" in postmenopausal women as those with insufficient sleep or difficulty falling or staying asleep have reported decreased cognitive performance including "verbal memory,

attention Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Atte ...

, and general cognition."

Depression

There is evidence linking depression and cognitive decline in postmenopausal women. Research suggests that increased

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

levels from depressive episodes may affect the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, area of the brain responsible for

episodic memory Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...

. Studies have also shown a correlation between depression and decreased cognitive performance including " processing speed,

verbal memory Verbal memory is a term used in cognitive psychology which refers to memory of words and other abstractions involving language. Verbal encoding Verbal encoding refers to the interpretation of verbal stimuli. Verbal encoding appears to be strongly ...

, and

working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...

" in postmenopausal women.

Hot flashes

There are studies indicating a correlation between frequency of

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es in postmenopausal women and a deficit in verbal memory performance. It is suggested that faster blood flow in the brain or higher

levels from hot flashes may cause changes in the brain and affect information processing and memory.

Surgical menopause

A 2019 systematic review and meta-analysis identified surgical menopause, especially when performed at or before the age of 45, as a substantial risk factor for cognitive decline and

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

Cardiac procedures

Axial PSIR MRI of a brain with multiple sclerosis lesions

Cardiac procedures such as invasive cerebral and coronary angiography, coronary artery bypass graft surgery (CABG), surgical

aortic valve replacement Aortic valve replacement is a procedure whereby the failing aortic valve of a patient's heart is replaced with an artificial heart valve. The aortic valve may need to be replaced because: * The valve is leaky (aortic insufficiency, also known as ...

, and

transcatheter aortic valve replacement Percutaneous aortic valve replacement (PAVR), also known as percutaneous aortic valve implantation (PAVI), transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR), is the replacement of the aortic valve o ...

(TAVR) have been found to increase the risk of cognitive decline in females as they been found to increase the incidence of brain

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

Mechanism

The mechanism of postmenopausal confusion is poorly understood due to simultaneous aging-related physiological changes, as well as differential diagnoses presenting with similar symptoms. Research remains ongoing.

Treatment

Overview

There are pharmacological and non-pharmacological considerations in improving the symptoms of postmenopausal confusion. Currently, no pharmacological agents are indicated to treat postmenopausal confusion, but research remains ongoing. Non-pharmacological strategies to manage postmenopausal confusion symptoms are utilized, with focus on diet and exercise.

Pharmacological

Hormone therapy

, also known as estrogen therapy, was previously a common treatment for postmenopausal confusion. However, more recent research indicates that ''hormone therapy is not an effective treatment'' for postmenopausal cognitive symptoms. A 2008 Cochrane review of 16 trials concluded that there is a body of evidence that suggests that hormone replacement therapy is unable to prevent cognitive decline or maintain cognitive function in healthy postmenopausal women when given over a short or long period of time. Conversely, studies have also suggested that the use of hormone replacement therapy are unlikely to have negative cognitive effects when used for their approved indications. Previous research suggested that increases in blood flow to the hippocampus and temporal lobe occurred from hormone therapy, improving postmenopausal confusion symptoms. More recent research no longer supports this, and is inconclusive as to the true effects of estrogen on hippocampal volume as studies show results differing from improved cognition and maintained hippocampal volume when hormone therapy is administered during menopause to results showing no obvious beneficial results. Research focusing on

adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produ ...

(ADPN) has yielded positive results in the development of possible treatments for postmenopausal confusion. A study has shown an association between higher levels of ADPN and increased cognitive performance in postmenopausal women. However, an ADPN receptor agonist has yet to be discovered.

Psychostimulant therapy

There is ongoing research regarding the efficacy of psychostimulant drugs such as

lisdexamphetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...

(Vyvanse) and

atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to impro ...

(Strattera) in treating postmenopausal and menopausal confusion.

Non-pharmacological

Diet

Individuals play an important role in maintaining their cognitive health. One way to achieve this is by the promotion of healthy nutrition. In particular, the

Mediterranean diet The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incor ...

, defined as being low in

saturated fat A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched c ...

and high in vegetable oils, showed improvement in aspects of cognitive function. This diet consists of low intake of sweets and eggs, moderate intakes of meat and fish, dairy products and red wine, and high intake of leafy green vegetables, pulses/legumes and nuts, fruits, cereal, and cold pressed extra virgin olive oil. Further analysis concluded that the Mediterranean diet supplemented by olive oil resulted in better cognition and memory as compared to the Mediterranean diet plus mixed nuts combination.

Supplementation

Soy isoflavones The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu and ...

(SIF), a type of

which can be found in soybeans, fruits and nuts, has been shown to improve cognitive outcomes in recent postmenopausal women of less than 10 years. This suggests that the initiation of SIF may have a critical margin of opportunity when used at a younger age in postmenopausal women. In addition to improved cognitive functions and visual memory, no evidence of harm from SIF supplementation was revealed with the dose ranges tested in multiple trials. Analysis of multiple randomized controlled trials have brought attention to

black cohosh ''Actaea racemosa'', the black cohosh, black bugbane, black snakeroot, rattle-top, or fairy candle ( syn. ''Cimicifuga racemosa''), is a species of flowering plant of the family Ranunculaceae. It is native to eastern North America from the extrem ...

and

red clover ''Trifolium pratense'', the red clover, is a herbaceous species of flowering plant in the bean family Fabaceae, native to Europe, Western Asia, and northwest Africa, but planted and naturalized in many other regions. Description Red clov ...

(which contain

) and its potential as an efficacious treatment of menopausal symptoms. Black cohosh did not reveal any evidence of risk of harm, but lack of good evidence cannot firmly conclude its safety. Overall, the results suggested that neither botanical treatments provided any cognitive benefits.

Resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources ...

, another bioactive compound derived from plants, has also shown to improve cognitive performance in postmenopausal women. There are ongoing trials studying the cognitive benefits of resveratrol in early versus late postmenopausal women. Chronic Ginkgo bilob supplementation has been shown to improve "mental flexibility" in "older and more cognitively impaired" postmenopausal women. However, a combined Ginkgo biloba and

ginger Ginger (''Zingiber officinale'') is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices ...

supplementation had no effect on memory or cognitive performance in postmenopausal women.

Dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It fun ...

(

DHEA Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...

) supplementation may improve cognition in women with postmenopausal confusion but does not benefit those without cognitive impairment. More long-term studies are required to study the efficacy of DHEA and its role in cognition and postmenopausal women.

Exercise

Regular

physical exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...

may prevent symptoms of postmenopausal confusion. Studies have shown an association between exercise and "lower rates of cognitive decline" in postmenopausal women. On the other hand, an inactive lifestyle has been strongly associated with "higher rates of cognitive decline" in postmenopausal women.

Mind-body therapy

Studies have shown benefits of mind-body therapies in women with postmenopausal symptoms including cognitive impairment.

Mindfulness Mindfulness is the practice of purposely bringing one's attention to the present-moment experience without evaluation, a skill one develops through meditation or other training. Mindfulness derives from ''sati'', a significant element of Hind ...

hypnosis Hypnosis is a human condition involving focused attention (the selective attention/selective inattention hypothesis, SASI), reduced peripheral awareness, and an enhanced capacity to respond to suggestion.In 2015, the American Psychologica ...

, and

yoga Yoga (; sa, योग, lit=yoke' or 'union ) is a group of physical, mental, and spiritual practices or disciplines which originated in ancient India and aim to control (yoke) and still the mind, recognizing a detached witness-consciou ...

may help decrease symptoms of insomnia, depression, or hot flashes in postmenopausal women which leads to better cognitive performance.

History

Presentation

Causes

Risk factors

Hypertension

Atherosclerosis and comorbidities

Insomnia

Depression

Hot flashes

Surgical menopause

Cardiac procedures

Mechanism

Treatment

Overview

Pharmacological

Hormone therapy

Psychostimulant therapy

Non-pharmacological

Diet

Supplementation

Exercise

Mind-body therapy

See also

References

Further reading