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Good morning everyone. Moving away from body mass changes for a moment and onto brain health and the impact of hormonal changes upon brain health.

As I wrote in the previous posts, it´s very possible to experience metabolic inflexibility as we move into post menopause. The brain’s use of fuel (glucose) begins to falter related to a decline in the efficiency of the mitochondria. ​ Think that you´ve been used to driving a car on petrol (glucose) all your life and then suddenly you switch to a hybrid car in your 40´s and have to get used to a different fuel (ketones and fatty acids). A whopping 85% of women experience brain related symptoms during menopause.

Research on the brain has shown that ”symptoms of perimenopause are largely neurological in nature”. Hot flashes, for instance, are not merely skin deep. They are a signal that there´s a shift happening inside your brain.

Other brain symptoms of (peri)menopause are:

  • Night sweats
  • Mood fluctuations (from irritability to anxiety attacks)
  • Disturbance in sleep patterns often leading to insomnia
  • Changes in cognitive function like memory, concentration (often called brain fog)
  • Dizziness and vertigo
  • Debilitating migraines
  • Severe depression
  • Panic attacks
  • Unexplained anger/rage
  • Restless legs and electric shock symptoms.

Why is this? – It gets a little complicated, so you may need to read a couple of times!

Oestrogen receptors are found in the mitochondria of each cell​. With changes to oestrogen levels, fluctuating in peri-menopause and dropping much lower in menopause, ​the amount of oestrogen available obviously influences our ​brain ​energy.

The brain can produce its own oestradiol from circulating levels of oestradiol and from cholesterol. Unfortunately oestrone (produced in menopause) is not useful in the brain. At menopause both circulating levels of oestradiol​ ​​in the body ​and levels in the brain decrease​, then gradually level off. This has a direct effect upon our mood and cognition and the increase in other menopausal symptoms such as hot flushes, night sweats, anxiety etc. The more our nervous system is affected in a negative way, the higher the likelihood of increased symptoms.

Fluctuations in oestradiol during the perimenopausal period are known to increase the sensitivity of women to psychosocial stress, which in turn is considered a phenomenon that primes the development of depressive disorders. Women are twice as likely to develop depression as men, which is probably related to dynamic fluctuations in sex hormones compared to men, whose sex hormones do not fluctuate and remain relatively constant throughout their lives.

Check out all of the parts of the brain that are regulated by oestrogen. These parts have special receptors that oestrogen plugs into, turning brain functions on or off. You will see on the diagram that the hypothalamus regulates body temperature. This area of the brain is also affected by stressors. It will also show where receptors are that help you with memory. As the receptors get less oestradiol it impacts certain functions.

The occurrence of depression is triggered by changes in blood oestradiol levels in females – simply put the drop in oestrogen produced by the ovaries. This may be the period before menstruation (termed, premenstrual dysphoric disorder, or PMDD), the postpartum period (termed, postpartum depression), and the perimenopausal period. Peri-menopausal women who have not had a previous episode of depression may experience depressed mood two-to-four times more often compared to pre-menopausal women. This risk is even higher in women with a history of depression.

Oestrogen can also modify the production and effects of endorphins – the brain’s “feel good chemicals’, so the big fluctuations in oestrogen levels from high to low during perimenopause to menopause may cause fluctuations in serotonin levels and affect how you feel.​ ​

High Oestrogen = higher Serotonin and feel good factor, but can blunt serotonin receptors leaving a female more vulnerable when oestrogen/serotonin dips i.e perimenopause!

Low oestrogen levels, directly tinker with the functioning of brain serotonin as well as cognitive function and other systems including insulin metabolism and cholesterol levels, sleep, hot flashes, night sweats, and vaginal dryness, all of which make it generally tough to cope.

Because of this stormful activity of oestrogen in perimenopause, many women experience irritability often described as overreacting, being intolerant of even small mistakes by others, over stressing about job performance, worrying about things they never used to worry about, and being easily overwhelmed by social situations with many people. Low oestrogen in post-menopause may cause more a more permanent state of low mood.

Female depression due to a fall in oestrogen, may be related to 5-hydroxytryptamine (5-HTP) deficiency. This compound is made from tryptophan when enough oestrogen is present from the amino acid tryptophan, and converted to serotonin. Tryptophan is found in avocados, poultry, bananas.

Progesterone availability during the reproductive years (when still ovulating) offers a stress-buffering and calming effect. Progesterone is produced by ovaries, placenta & adrenal glands and due to its small size and ability be fat soluble, progesterone easily crosses the blood brain barrier. Also why this hormone helps with sleep.

A study in 2021 has shown that, women with higher progesterone levels seem to be more resilient than women with lower progesterone levels, irrespective of the perimenopausal status. Further analyses revealed that women with higher progesterone levels experience significantly higher life satisfaction, lower perceived stress, and lower depressive symptoms than women with lower progesterone levels.

However, progesterone changes (drops) cause temporarily increased risk mood symptoms. The brain can recalibrate as receptors become accustomed to different hormone levels.

Oestrogen & Progesterone have a strong effect on Monoamine oxidase (MAOA) a protein that starts the breakdown of serotonin and other neurotransmitters. Fluctuating oestradiol levels affect the binding of monoamine oxidase A to a neurotransmitter, and increases the risk of severe depression in women by affecting the stress response and emotional regulation in the brain network.

Therefore, oestradiol treatment needs to be considered in the early menopausal transition period before the decline of ovarian hormone level permanently affects the serotonin function.

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