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The menopausal transition is characterised by declining ovarian function, erratic hormonal flux and a wide range of associated possible signs and symptoms with significant variation from one woman to the next. Commonly experienced symptoms may include changes in cognitive function, vaginal dryness, hot flashes, night sweats and poor sleep. Many women may experience anxiety, low mood and reduced ability to cope with stress, all of which may significantly affect quality of life during this time.

In this article we take a closer look at mood changes during the menopausal transition and highlight some key nutrients and ingredients that may be useful to consider.

Gender differences in mood disorders
Although both sexes can be significantly affected by mood disorders, the lifetime prevalence is higher in women than men, with some estimates suggesting it may be as much as twice as high.1 This increase begins during adolescence and continues through the menopausal transition. And whilst we are a long way from fully understanding the underlying causality for this gender difference, much scientific research is now focused on how neurotransmitter systems are affected by fluctuating sex hormones and changes in hormonal status over the course of a woman’s life.2,3

Menopausal transition
There is much individual variation in the trajectory of hormonal changes during the menopause and every woman will experience this transition in a unique way. Many factors can influence this including genetic differences, diet, lifestyle, psychosocial, physiological and environmental factors. During the earlier stages of perimenopause, oestrogen levels may be elevated whilst progesterone decreases. As the transition progresses oestrogen levels can become highly erratic, and progesterone may often be low. Eventually both oestrogen and progesterone production decline towards the end of the menopausal transition. It is fair to say that perhaps the only consistent feature is that most women undergoing a natural transition to menopause are exposed to highly erratic hormonal flux.

Menopause and mood
Research shows that there is an increased likelihood of mood changes during times of hormonal fluctuation. Studies have also shown increased incidence of low mood and anxiety in women during the menopausal transition.4 We know that there are complex and still not fully understood interactions between sex hormones such as oestrogen and progesterone and important brain neurotransmitters such as serotonin (the ‘feel-good’ neurotransmitter), GABA (the ‘calming’ neurotransmitter) and dopamine (the ‘pleasure’ neurotransmitter), all of which have vital roles to play in supporting balanced mood.

One key takeaway here is that the hormonal flux that many women will experience during the menopausal transition has potential to impact key neurotransmitters involved in mood.

Oestrogenic regulation of neurotransmitters
Much research now demonstrates the interaction between oestrogen and neurotransmitter systems involved in mood including dopamine, serotonin and GABA. Of particular interest is the relationship between oestrogen and serotonin. Research consistently shows that oestrogen has many important roles to play in supporting serotonin synthesis, transport, uptake, receptors and even postsynaptic responsiveness. Oestrogen can be described as a “serotonergic agonist that responds via multiple mechanisms in brain regions involved in mood regulation”.4

Progesterone, serotonin & GABA
Much less is talked and written about the impact of declining levels of progesterone on mood during the menopausal transition, however it is no less significant. In fact, progesterone has a broad spectrum of actions in the brain – as ‘hormone, neurosteroid and neuroprotectant’.5 Progesterone has been shown to influence serotonin via modifying the expression of genes and proteins relating to this ‘feel-good’ neurotransmitter.6

Progesterone can also be converted to a downstream progesterone neuroactive metabolite called allopregnanolone. Allopregnanolone has been shown to interact with GABA (the ‘calming’ neurotransmitter) receptors and has potential to produce anxiolytic and mood supportive effects.7

There remain significant gaps in understanding of the GABA system during hormonally dynamic periods such as the menopausal transition but this is certainly a fascinating area of research to keep a close eye on.8

Natural toolkit of nervous system support
Clearly, supporting mood during the menopausal transition requires an integrated, individualised and multi-faceted approach. And whilst the complex interactions between hormonal fluctuations and neurotransmitter systems are still not fully understood, it still seems prudent to consider what we have in our natural toolkit of nervous system support as part of this integrated approach.

Here are some key nutrients and ingredients to consider:

Magnesium glycinate
Magnesium glycinate sits right at the top of this list for very good reason. Multiple studies have demonstrated improved stress response, anti-depressant and anti-anxiety effects of magnesium supplementation. In fact, magnesium’s calming and soothing effects are so widespread it is commonly referred to as ‘nature’s tranquiliser’ and this is what makes magnesium such an important support during the menopause.9-11 

Magnesium has many important roles to play in calming the nervous system; of particular relevance here is its potential to interact with the GABA system and support this calming neurotransmitter.12 In a 2017 systematic review, researchers concluded that existing evidence is suggestive of a beneficial effect of magnesium supplementation on anxiety.13 In another 2017 randomised clinical trial involving 126 men and women with mild to moderate depression, 6 weeks of daily treatment with 248mg magnesium significantly improved depression scores. Symptoms of anxiety also improved.14

When you take magnesium in the supplement form of magnesium glycinate you also get the added benefit of the amino acid glycine which readily crosses the blood brain barrier and has an additional calming effect on the brain. It is also interesting to note that some studies have shown improvements in sleep following glycine supplementation.15-17 This has additional significance since sleep may often be impacted during the menopausal transition and taking steps to improve sleep has the potential to positively influence mood and anxiety.

Vitamin B6
Whilst it is crucial to ensure regular and optimal intake of the full range of B vitamins to support the nervous system, vitamin B6 deserves special mention here because it has an important role to play in supporting production of both GABA and serotonin.18 Vitamin B6 can be taken in the active supplement form of pyridoxal-5-phosphate.

Folate (5-MTHF)
Numerous studies have now found an association between low serum folate and incidence of depression. In addition, some research has identified a higher prevalence of genetic variations in the methylene tetrahydrofolate reductase (MTHFR) enzyme in depressed compared to non-depressed individuals. For those with the MTHFR variation, supplementation is generally recommended with a methylated or ‘active’ form of folate such as 5-methyltetrahydrofolate (5-MTHF).19,20

Ashwagandha (KSM-66®)
Ashwagandha is an Ayurvedic herb with a long history of use. It is classified as an adaptogen, which describes its ability to regulate physiologic processes and stabilise the body’s response to stress. Ashwagandha contains over 35 chemical constituents and has a wide range of activity. In a 2014 systematic review of human trial results published in the Journal of Alternative and Complementary Medicine, researchers concluded that, “intervention with ashwagandha resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales.”21 Double-blind, placebo-controlled trials have been carried out on the KSM-66® form of ashwagandha, results of which support the use of this unique form of ashwagandha for supporting balanced mood, ability to cope with stress, relaxation and calm.22-31

Rhodiola rosea
Rhodiola rosea has a long history of traditional use as an adaptogen for enhancing mental and physical performance and for its stress-protective effects. And more recently, it has been widely researched for a range of beneficial actions. In a small randomised controlled trial carried out in 2015 researchers found that R. rosea may help to improve neuropsychological symptoms such as anxiety, mood and stress intolerance.32

Learn More
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